Diabetes Mellitus, Type 2
Conditions
Keywords
switch study, albiglutide, glucagon-like peptide-1 receptor agonist, Type 2 diabetes mellitus, basal-bolus insulin therapy
Brief summary
This Phase IIIb, randomized, open-label, parallel group, active control, multicenter, treat to-target study of 26 weeks' treatment duration will evaluate the efficacy and safety of once-weekly albiglutide as replacement of prandial insulin in subjects with type 2 diabetes mellitus (T2DM) failing to achieve adequate glycemic control on their current basal bolus insulin regimen (with or without metformin). Approximately 794 subjects will be randomly assigned in a 1:1 ratio to 1 of 2 treatment groups: albiglutide + insulin glargine (with insulin lispro discontinuation at Week 4) (with or without metformin) or to intensification of insulin glargine + insulin lispro (with or without metformin). The study will comprise 4 study periods : Screening (2 weeks), Standardization (4 weeks), Treatment (26 weeks), and Post treatment Follow up (4 weeks). The total duration of a subject's participation will be approximately 36 weeks.
Interventions
DRUGAlbiglutide
Albiglutide is intended for self-administration as a SC injection. It is provided as a fixed dose of 30 mg of albiglutide or 50 mg of albiglutide in a 0.5 mL injection volume, fully disposable pen injector
Insulin glargine and insulin lispro will be provided as injection pens for SC injection
Sponsors
PPD Development, LP
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female, 18 years of age or older (inclusive at the time of Screening) with T2DM * HbA1c \>= 7.0% and \<= 9.0% at Screening. * Currently treated with a basal-bolus insulin regimen (with or without metformin) for at least 3 months before Screening. The subject must be taking the following: * Basal insulin (1 or 2 daily injections of neutral protamine Hagedorn insulin, insulin glargine, insulin detemir, or insulin degludec) AND * Bolus insulin (at least 2 injections of regular insulin, insulin glulisine, insulin aspart, or insulin lispro) with a total daily dose of bolus insulin \<= 70 units * In addition, the total daily dose of insulin must be \<= 140 units * If taking metformin, a stable dose for at least 8 weeks before Screening Note: Subject should not have received any other antidiabetic medication within 30 days before screening (e.g., glucagon-like peptide-1 receptor (GLP-1R) agonist, dipeptidyl peptidase-IV inhibitor, SU, or thiazolidinedione). Subjects receiving commercially available premixed basal and prandial insulin are not eligible for this study. * Fasting C-peptide \>= 0.8 nanogram (ng) per milliliter (mL) \[\>= 0.26 nanomoles per litre (nmol/L)\] * Body mass index \<= 40 kilogram per square meter( kg/m\^2) * Thyroid-stimulating hormone (TSH) level is normal or clinically euthyroid as demonstrated by further thyroid tests (e.g., free T4) * Female subjects of childbearing potential (i.e., not surgically sterile and/or not postmenopausal) must be practicing adequate contraception (as defined in the protocol) for the duration of participation in the study including the 4-week post treatment Follow-up Period.. * Willing and able to comply with all study procedures including performance of frequent self-monitored blood glucose (SMBG) profiles according to the protocol * Able and willing to provide written informed consent
Exclusion criteria
* Type 1 diabetes mellitus * History of cancer that has not been in full remission for at least 3 years before Screening. (A history of squamous cell or basal cell carcinoma of the skin or treated cervical intra-epithelial neoplasia I or II is allowed) * Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 * Current symptomatic biliary disease or history of acute or chronic pancreatitis * Severe gastroparesis, i.e., requiring regular therapy within 6 months before Screening * History of significant GI surgery that in the opinion of the investigator is likely to significantly affect upper GI or pancreatic function \[e.g., gastric bypass and banding, antrectomy, Roux-en-Y bypass, gastric vagotomy, small bowel resection, or surgeries thought to significantly affect upper GI function\] * History of severe hypoglycemia unawareness * Diabetic complications (e.g., active proliferative retinopathy or severe diabetic neuropathy) or any other clinically significant abnormality (including a psychiatric disorder) that, in the opinion of the investigator, may pose additional risk in administering the investigational product * Clinically significant CV and/or cerebrovascular disease within 3 months before Screening including, but not limited to, the following: * Stroke or transient ischemic attack * Acute coronary syndrome (myocardial infarction \[MI\] or unstable angina not responsive to nitroglycerin) * Cardiac surgery or percutaneous coronary procedure * Current or history of heart failure (New York Heart Association class III or IV) * Alanine aminotransferase (ALT) \>2.5 × upper limit of normal (ULN) or bilirubin \>1.5 × ULN (isolated bilirubin \>1.5 × ULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%) * Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones). (Chronic stable hepatitis B and C are acceptable if subject otherwise meets entry criteria and is not on active antiviral treatment \[e.g., presence of hepatitis B surface antigen or positive hepatitis C test result within 3 months of Screening\]) * Hemoglobin \<11 gram (g) per (dL) \[\<110 g/L\] for male subjects and \<10 g/dL (\<100 g/L) for female subjects at Screening * Estimated glomerular filtration rate (eGFR) \<= 30 millilitre per minute per 1.73 square meters (mL/min/1.73 m\^2) (calculated using the Modification of Diet in Renal Disease \[MDRD\] formula) at Screening Note: As the use of metformin in subjects with varying degrees of renal function may differ from country to country, use of metformin should be in accordance with the metformin product label within the participating country. * Fasting triglyceride level \>750 mg/dL at Screening * Hemoglobinopathy that may affect proper interpretation of HbA1c * Known allergy to albiglutide or any product components (including yeast and human albumin), any other GLP-1 analogue, insulin, or other study medication's excipients OR other contraindications (per the prescribing information) for the use of potential study medications (e.g., insulin glargine, insulin lispro) * Use of oral or systemically injected glucocorticoids within the 3 months before randomization or high likelihood of a requirement for prolonged treatment (\>1 week) in the 6 months following randomization. However, short courses of oral steroids (single dose or multiple doses for up to 7 days) may be permitted provided these cases are discussed with the medical monitor. Inhaled, intra-articular, epidural, and topical corticosteroids are allowed * Female subject is pregnant (confirmed by laboratory testing) or lactating * Receipt of any investigational drug within the 30 days or 5 half-lives, whichever is longer, before Screening, a history of receipt of an investigational antidiabetic drug within the 3 months before randomization, or receipt of albiglutide in previous studies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | Baseline (Day -1) and Week 26 | HbA1c is glycosylated hemoglobin. It was measured at Baseline and at Week 26. The analysis was conducted using mixed-effect model with repeated measures (MMRM). The model included HbA1c change from Baseline as the dependent variable; treatment, region, age category, current metformin use, visit week, treatment-by-week interaction, and Baseline HbA1c-by-week interaction as fixed effects; Baseline HbA1c as a continuous covariate; and participant as a random effect. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Severe or Documented Symptomatic Hypoglycemia Through Week 26 | Up to Week 26 | Severe hypoglycemia was considered as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal was considered sufficient evidence that the event was induced by a low plasma glucose concentration. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration \<=70 milligrams per deciliters (mg/dL) (\<=3.9 millimoles per liters \[mmol/L\]). |
| Change From Baseline in Body Weight at Week 26 | Baseline (Day -1) and Week 26 | Body weight was measured to the nearest 0.1 kilogram on a standard calibrated scale. Participants dressed in light indoor clothes (no coat, jacket, etc.) without shoes and with a voided bladder. The same equipment was used wherever possible. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value. |
| Change From Baseline to Week 26 in Body Weight | Baseline (Day -1) to Week 26 | Body weight was measured to the nearest 0.1 kilogram on a standard calibrated scale. Participants dressed in light indoor clothes (no coat, jacket, etc.) without shoes and with a voided bladder. The same equipment was used wherever possible. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value. Change from Baseline to Week 26 in body weight are presented. FA Population was analyzed. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. |
| Total Daily Insulin Dose at Week 26 | Week 26 | Insulin dose at Week 26 was defined as the prescribed insulin dose at Week 25. Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily insulin dose at Week 26 is presented. Only those participants available at the specified time points were analyzed. |
| Change From Baseline to Week 26 in HbA1c | Baseline to Week 26 | HbA1c is glycosylated hemoglobin and was measured up to Week 26. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | Baseline and Week 26 | FPG was measured at Baseline (Day -1). FPG values for all participants at Week 26 were not collected due to an error in the protocol and were imputed with the fasting serum glucose (FSG) values at this time point. The imputation of the FPG at Week 26 from the FSG values was deemed acceptable from the results of the analysis of the correlation between FPG and FSG at the screening visit. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value. |
| Change From Baseline to Week 26 in FPG | Baseline to Week 26 | FPG was measured at Baseline (Day -1) up to Week 26. FPG values for all participants at Week 26 were not collected due to an error in the protocol and were imputed with the FSG values at this time point. The imputation of the FPG at Week 26 from the FSG values was deemed acceptable from the results of the analysis of the correlation between FPG and FSG at the screening visit. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value. |
| Number of Participants Achieving HbA1c <7.0% at Week 26 | Week 26 | HbA1c is glycosylated hemoglobin. Number of participants achieving a HbA1c \<7.0% at Week 26 are presented. |
| Number of Participants Achieving HbA1c <7.0% up to Week 26 | Up to Week 26 | HbA1c is glycosylated hemoglobin. Number of participants achieving a HbA1c \<7.0% up to Week 26 are presented. |
| Number of Participants Achieving a HbA1c <6.5% at Week 26 | Week 26 | Number of participants achieving a HbA1c \<6.5% at Week 26 are presented. |
| Number of Participants Achieving a HbA1c <6.5% up to Week 26 | Up to Week 26 | Number of participants achieving a HbA1c \<6.5% up to Week 26 are presented. |
| Number of Participants Who Met Prespecified Criteria for Severe, Persistent Hyperglycemia at Week 26 | Week 26 | Meeting prespecified criteria for severe, persistent hyperglycemia was defined operationally as being withdrawn due to lack of efficacy as recorded on the Treatment Discontinuation and Study Conclusion electronic case report form pages. Number of participants who met prespecified criteria for severe, persistent hyperglycemia at Week 26 are presented. |
| Number of Participants Meeting Prespecified Criteria for Severe, Persistent Hyperglycemia up to Week 26 | Up to Week 26 | Meeting prespecified criteria for severe, persistent hyperglycemia was defined operationally as being withdrawn due to lack of efficacy as recorded on the Treatment Discontinuation and Study Conclusion electronic case report form pages. Number of participants meeting prespecified criteria for severe, persistent hyperglycemia up to Week 26 are presented. |
| Total Daily Insulin Dose at Week 4, Week 10 and Week 18 | Weeks 4, 10, and 18 | Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily insulin dose at Week 4, Week 10 and Week 18 is presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. |
| Total Daily Basal Insulin (Insulin Glargine) at Week 4, 10, 18, and 26 Visits | Weeks 4, 10, 18, and 26 | Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily basal insulin (insulin glargine) at Week 4, 10, 18, and 26 visits is presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. |
| Total Daily Bolus Insulin (Insulin Lispro) at Week 4, 10, 18, and 26 Visits | Weeks 4, 10, 18, and 26 | Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily bolus insulin (insulin lispro) at Week 4, 10, 18, and 26 visits is presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. |
| Total Number of Weekly Insulin Injections to Achieve Glycemic Control at Baseline/Randomization and Week 4, 10, 18, and 26 | Baseline (Day -1) and Weeks 4, 10, 18 and 26 | Total number of weekly insulin injections (7 days) to achieve glycemic control at Baseline/Randomization and Week 4, 10, 18, and 26 are presented. Only those participants available at the specified time points were analyzed represented by n=X,X in category titles. |
| Percentage of Participants Achieving HbA1c <7.0% Without Weight Gain at Week 26 | Week 26 | Percentage of participants achieving HbA1c \<7.0% without weight gain are presented. |
| Percentage of Participants Achieving HbA1c <7.0% Without Severe or Documented Symptomatic Hypoglycemia at Week 26 | Week 26 | Percentage of participants achieving HbA1c \<7.0% without severe or documented symptomatic hypoglycemia are presented. |
| Number of Participants Treated With Once-weekly Albiglutide That Were Able to Discontinue Insulin Lispro at Week 4 and Did Not Meet Prespecified Criteria for Severe, Persistent Hyperglycemia Through Week 26 | Up to Week 26 | Participants who did not meet prespecified criteria for severe, persistent hyperglycemia through Week 26 were those participants treated with once-weekly albiglutide that were able to replace prandial insulin without lispro re-introduction through Week 26. Number of participants treated with once-weekly albiglutide that were able to discontinue insulin lispro at Week 4 and did not meet prespecified criteria for severe, persistent hyperglycemia through Week 26 have been presented. |
| Number of Participants With On-therapy Adverse Events (AE) and Serious AE (SAE), and AE Leading to Discontinuation of Randomized Study Medication | Up to Week 26 | AE is any untoward medical occurrence in a participant, temporally associated with use of medicinal product (MP), whether or not considered related to MP. AE can be any unfavorable, unintended sign (also an abnormal laboratory finding), symptom, or disease (new/exacerbated) temporally associated with use of MP. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, or is a congenital anomaly/birth defect or is medically significant or all events of possible drug induced liver injury with hyperbilirubinemia. Safety Population: All participants who received at least 1 dose of randomized study medication. A participant randomized to Albiglutide + Insulin glargine by mistake received Insulin Lispro + Insulin Glargine instead. Since this participant received actual treatment as Insulin Lispro + Insulin Glargine, was summarized as such in Safety Population. |
| Number of Participants With Other AE of Special Interest | Up to Week 26 | AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with use of a MP, whether or not considered related to MP. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with use of MP. AE of special interest included hypoglycemic events, cardiovascular events, gastrointestinal events, injection site reactions, potential systemic allergic reactions, pancreatitis, pancreatic cancer, malignant neoplasms following treatment with insulin, diabetic retinopathy events, appendicitis, liver events, pneumonia, and atrial fibrillation/flutter. |
| Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26 | Up to Week 26 | Hypoglycemic events with confirmed home plasma glucose monitoring \<3.9 millimoles per Liter and/or requiring third party intervention were severe, documented symptomatic (DS) and asymptomatic hypoglycemic events. Participants with more than one hypoglycemic event are counted in all categories reported. Any severe, documented symptomatic, and asymptomatic hypoglycemic events in 3-month intervals (i.e., from Day 0 to Week 12, \>Week 12 to Week 26) are presented. |
| Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria) | Up to Week 26 | The American Diabetes Association has categorized hypoglycemic events as follows: Severe, documented symptomatic, asymptomatic, probably symptomatic and pseudohypoglycemia. Number of participants with hypoglycemic events in total are also presented. |
| Number of Participants With Daytime and Nocturnal Hypoglycemia | Up to Week 26 | Daytime hypoglycemia was defined as hypoglycemic events with an onset between 06:00 hours and 00:00 hours (inclusive), and nocturnal hypoglycemia (in total and by category), defined as hypoglycemic events with an onset between 00:01 hours and 05:59 hours (inclusive). Number of participants with daytime and nocturnal hypoglycemia (in total and by category) are presented. |
| Number of Participants With Hypoglycemia With Blood Glucose <56 Milligrams Per Deciliter (mg/dL) (<3.1 Millimoles Per Liter [mmol/L]), Regardless of Symptoms | Up to Week 26 | Number of participants with hypoglycemia with blood glucose \<56 mg/dL (\<3.1 mmol/L), regardless of symptoms are presented. |
| Number of Participants With Hematology Values of Clinical Concern | Up to 30 weeks | Hematology parameters included basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, monocytes, neutrophils, neutrophil bands, platelets, red blood cell (RBC) count, segmented neutrophils and white blood cell (WBC) count. The potential clinical concern values were: Hematocrit \>0.05 below lower limit of normal (LLN) and \>0.04 above upper limit of normal (ULN), hemoglobin: \>20 grams cells per Liter (g/L) below LLN and \>10 g/L above ULN, lymphocytes: \<0.5 x LLN, neutrophils: \<1 giga cells per liter (GI/L), platelets: \<80 GI/L and \>500 GI/L, segmented neutrophils: \<0.5 x LLN, RBC count: \>1 GI/L below LLN and \>5 GI/L above ULN and none for basophils, eosinophils, monocytes, neutrophil bands and RBC count. Only those parameters for which at least one value of potential clinical concern was reported are summarized. |
| Number of Participants With Clinical Chemistry Values of Clinical Concern | Up to 30 weeks | Clinical chemistry parameters and their potential clinical concern values were: albumin (\>5 g/L above ULN or below LLN), alkaline phosphatase(\>3 x ULN), alanine aminotransferase (\>3 x ULN), aspartate aminotransferase (\>3 x ULN), carbon dioxide content (\<16 millimoles per Liter \[mmol/L\] and \> 40 mmol/L), blood urea nitrogen (\>2 x ULN), calcium (\<1.8 mmol/L and \>3.0 mmol/L), chloride (none), creatinine (\>159 micromoles/Liter), direct bilirubin (\>1.35 x ULN), gamma glutamyl transferase (\>3 x ULN), glucose (fasting) (\<3 mmol/L and \>22 mmol/L), magnesium (\<0.411 mmol/L and \>1.644 mmol/L), phosphate (\>0.323 mmol/L above ULN or below LLN), potassium (\>0.5 mmol/L below LLN and \>1.0 mmol/L above ULN), sodium (\>5 mmol/L above ULN or below LLN), triglycerides (\> 9.04 mmol/L), total bilirubin (\>1.5 x ULN), total protein (\>15 g/L above ULN or below LLN) and uric acid (\>654 umol/L). Only those parameters for which at least one value of potential clinical concern was reported are summarized. |
| Mean Urine Albumin/Creatinine Ratio at Week 0 and Week 26 | Week 0 and Week 26 | Urine samples were collected for analysis of albumin/creatinine ratio. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Mean urine albumin/creatinine ratio at Week 0 and Week 26 are presented. |
| Mean Albumin at Week 0 and Week 26 | Week 0 and Week 26 | Urine samples were collected for analysis of albumin. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Mean albumin at Week 0 and Week 26 are presented. |
| Mean Creatinine at Week 0 and Week 26 | Week 0 and Week 26 | Urine samples were collected for analysis of creatinine. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Mean creatinine at Week 0 and Week 26 are presented. |
| Mean Specific Gravity at Week 0 and Week 26 | Week 0 and Week 26 | Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. A urinary specific gravity measurement is a routine part of urinalysis. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. |
| Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | Week 0 and Week 26 | Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Safety Population was analyzed. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. |
| Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | Week 0 and Week 26 | Urine samples were collected for analysis of erythrocyte count. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Number of participants with different number of erythrocytes in urine at Week 0 and Week 26 are presented. |
| Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | Week 0 and Week 26 | Urine samples were collected for analysis of leukocyte count. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Number of participants with different number of leukocytes in urine at Week 0 and Week 26 are presented. |
| Change From Baseline in Total Cholesterol (TC), Low-density Lipoprotein Cholesterol (LDL-c), High Density Lipoprotein (HDL-c), Triglycerides (TG) and Free Fatty Acids (FFA) at Week 10 and Week 26 | Baseline, Week 10 and Week 26 | Lipid parameters included TC, LDL-c, HDL-c, TG and FFA. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value. LDL-c and FFA were collected as part of the lipid panel and results were reviewed by investigators for individual participants. Change from Baseline at Week 10 and Week 26 was not assessed for these parameters. Analysis of these parameters was not a specific study objective and would not have any impact on study conclusions. Only those parameters with data values have been presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. |
| Number of Participants With Vital Signs of Clinical Concern | Up to 30 weeks | Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate values. Assessment of vitals were performed with the participant in a semi recumbent or seated position having rested in this position for at least 5 minutes before each reading. The potential clinical concern values were: SBP: \<100 millimeters of mercury (mmHg) and \>170 mmHg, DBP: \<50 mmHg and \>110 mmHg and pulse rate: \<50 beats per minute (bpm) and \> 120 bpm. Number of participants with vital signs of clinical concern are presented. |
| Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Parameters | Up to 30 weeks | A single 12-lead ECG recordings were performed in a participant in semi recumbent position for 10 to 15 minutes before obtaining the ECG. Any clinically significant favorable and unfavorable findings are reported. |
| Percentage of Participants Achieving HbA1c <7.0% Without Weight Gain and Without Severe or Documented Hypoglycemia at Week 26 | Week 26 | Percentage of participants achieving HbA1c \<7.0% without weight gain and without severe or documented hypoglycemia are presented. |
Countries
Brazil, Canada, France, Germany, Hungary, Italy, Mexico, Philippines, Poland, South Africa, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
This study was conducted from 21-Nov-2014 to 24-Jul-2017 at 186 centers in 14 countries: Canada, United States of America, Mexico, Brazil, Hungary, Poland, France, Germany, Italy, Spain, United Kingdom, Korea, Philippines and South Africa.
Pre-assignment details
A total of 2004 participants were screened, of which 973 participants were screen failures and 160 participants were re-screened. A total of 1031 participants then entered the standardization period, of which 217 participants were standardization failures. A total of 814 participants were randomized in the study.
Participants by arm
| Arm | Count |
|---|---|
| Albiglutide + Insulin Glargine During standardization period, participants transitioned from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. Eligible participants received Albiglutide 30 mg weekly SC injection during the treatment period and insulin lispro dose was down-titrated to half that used in the standardization period. At Week 4, Albiglutide was up-titrated to 50 mg weekly SC injection and insulin lispro was stopped for the remainder of the treatment period. | 402 |
| Insulin Lispro + Insulin Glargine During standardization period, participants transitioned from basal bolus regimen received during screening period to insulin glargine plus insulin lispro. Eligible participants continued with the same doses as at the end of the standardization period and doses were adjusted according to protocol-defined insulin titration algorithms. Participants received Insulin Glargine along with Insulin Lispro during the treatment period. | 412 |
| Total | 814 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 14 | 9 |
| Overall Study | Lack of Efficacy | 3 | 3 |
| Overall Study | Lost to Follow-up | 3 | 3 |
| Overall Study | Other | 0 | 1 |
| Overall Study | Physician Decision | 5 | 12 |
| Overall Study | Protocol defined stopping criteria | 1 | 3 |
| Overall Study | Protocol Violation | 6 | 8 |
| Overall Study | Study terminated by sponsor | 11 | 11 |
| Overall Study | Withdrawal by Subject | 8 | 12 |
Baseline characteristics
| Characteristic | Albiglutide + Insulin Glargine | Insulin Lispro + Insulin Glargine | Total |
|---|---|---|---|
| Age, Continuous | 58.0 Years STANDARD_DEVIATION 9.4 | 58.1 Years STANDARD_DEVIATION 9.49 | 58.1 Years STANDARD_DEVIATION 9.44 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 43 Participants | 28 Participants | 71 Participants |
| Race/Ethnicity, Customized Asian-Central/South Asian (A) Heritage (H) | 5 Participants | 8 Participants | 13 Participants |
| Race/Ethnicity, Customized Asian-Japanese H/East AH/South East AH | 25 Participants | 24 Participants | 49 Participants |
| Race/Ethnicity, Customized Black or African American | 37 Participants | 32 Participants | 69 Participants |
| Race/Ethnicity, Customized Multiple-Black or African American and White | 7 Participants | 5 Participants | 12 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 1 Participants | 3 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 284 Participants | 312 Participants | 596 Participants |
| Sex: Female, Male Female | 228 Participants | 214 Participants | 442 Participants |
| Sex: Female, Male Male | 174 Participants | 198 Participants | 372 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 400 | 1 / 413 |
| other Total, other adverse events | 114 / 400 | 101 / 413 |
| serious Total, serious adverse events | 23 / 400 | 31 / 413 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26
HbA1c is glycosylated hemoglobin. It was measured at Baseline and at Week 26. The analysis was conducted using mixed-effect model with repeated measures (MMRM). The model included HbA1c change from Baseline as the dependent variable; treatment, region, age category, current metformin use, visit week, treatment-by-week interaction, and Baseline HbA1c-by-week interaction as fixed effects; Baseline HbA1c as a continuous covariate; and participant as a random effect. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value.
Time frame: Baseline (Day -1) and Week 26
Population: FA Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | -1.04 Percentage of glycosylated hemoglobin | Standard Error 0.041 |
| Insulin Lispro + Insulin Glargine | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | -1.10 Percentage of glycosylated hemoglobin | Standard Error 0.04 |
p-value: <0.000195% CI: [-0.05, 0.17]t-test, 2 sided
Secondary
Change From Baseline in Body Weight at Week 26
Body weight was measured to the nearest 0.1 kilogram on a standard calibrated scale. Participants dressed in light indoor clothes (no coat, jacket, etc.) without shoes and with a voided bladder. The same equipment was used wherever possible. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value.
Time frame: Baseline (Day -1) and Week 26
Population: FA Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Change From Baseline in Body Weight at Week 26 | -1.95 Kilograms | Standard Error 0.207 |
| Insulin Lispro + Insulin Glargine | Change From Baseline in Body Weight at Week 26 | 2.43 Kilograms | Standard Error 0.205 |
p-value: <0.000195% CI: [-4.93, -3.82]t-test, 2 sided
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26
FPG was measured at Baseline (Day -1). FPG values for all participants at Week 26 were not collected due to an error in the protocol and were imputed with the fasting serum glucose (FSG) values at this time point. The imputation of the FPG at Week 26 from the FSG values was deemed acceptable from the results of the analysis of the correlation between FPG and FSG at the screening visit. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value.
Time frame: Baseline and Week 26
Population: FA Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | -2.01 Millimoles per Liter | Standard Error 0.12 |
| Insulin Lispro + Insulin Glargine | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 26 | -1.46 Millimoles per Liter | Standard Error 0.121 |
p-value: 0.000495% CI: [-0.86, -0.25]t-test, 2 sided
Secondary
Change From Baseline in Total Cholesterol (TC), Low-density Lipoprotein Cholesterol (LDL-c), High Density Lipoprotein (HDL-c), Triglycerides (TG) and Free Fatty Acids (FFA) at Week 10 and Week 26
Lipid parameters included TC, LDL-c, HDL-c, TG and FFA. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value. LDL-c and FFA were collected as part of the lipid panel and results were reviewed by investigators for individual participants. Change from Baseline at Week 10 and Week 26 was not assessed for these parameters. Analysis of these parameters was not a specific study objective and would not have any impact on study conclusions. Only those parameters with data values have been presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.
Time frame: Baseline, Week 10 and Week 26
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide + Insulin Glargine | Change From Baseline in Total Cholesterol (TC), Low-density Lipoprotein Cholesterol (LDL-c), High Density Lipoprotein (HDL-c), Triglycerides (TG) and Free Fatty Acids (FFA) at Week 10 and Week 26 | TC: Week 10, n=376,393 | -0.244 Millimoles per Liters | Standard Deviation 0.8047 |
| Albiglutide + Insulin Glargine | Change From Baseline in Total Cholesterol (TC), Low-density Lipoprotein Cholesterol (LDL-c), High Density Lipoprotein (HDL-c), Triglycerides (TG) and Free Fatty Acids (FFA) at Week 10 and Week 26 | TC: Week 26, n=348,351 | -0.059 Millimoles per Liters | Standard Deviation 0.8721 |
| Albiglutide + Insulin Glargine | Change From Baseline in Total Cholesterol (TC), Low-density Lipoprotein Cholesterol (LDL-c), High Density Lipoprotein (HDL-c), Triglycerides (TG) and Free Fatty Acids (FFA) at Week 10 and Week 26 | HDL-c: Week 10, n=376,393 | -0.041 Millimoles per Liters | Standard Deviation 0.1944 |
| Albiglutide + Insulin Glargine | Change From Baseline in Total Cholesterol (TC), Low-density Lipoprotein Cholesterol (LDL-c), High Density Lipoprotein (HDL-c), Triglycerides (TG) and Free Fatty Acids (FFA) at Week 10 and Week 26 | HDL-c: Week 26, n=348,351 | -0.013 Millimoles per Liters | Standard Deviation 0.2102 |
| Albiglutide + Insulin Glargine | Change From Baseline in Total Cholesterol (TC), Low-density Lipoprotein Cholesterol (LDL-c), High Density Lipoprotein (HDL-c), Triglycerides (TG) and Free Fatty Acids (FFA) at Week 10 and Week 26 | TG: Week 10, n=376,393 | -0.039 Millimoles per Liters | Standard Deviation 1.3563 |
| Albiglutide + Insulin Glargine | Change From Baseline in Total Cholesterol (TC), Low-density Lipoprotein Cholesterol (LDL-c), High Density Lipoprotein (HDL-c), Triglycerides (TG) and Free Fatty Acids (FFA) at Week 10 and Week 26 | TG: Week 26, n=348,351 | 0.025 Millimoles per Liters | Standard Deviation 1.1949 |
| Insulin Lispro + Insulin Glargine | Change From Baseline in Total Cholesterol (TC), Low-density Lipoprotein Cholesterol (LDL-c), High Density Lipoprotein (HDL-c), Triglycerides (TG) and Free Fatty Acids (FFA) at Week 10 and Week 26 | TG: Week 10, n=376,393 | -0.065 Millimoles per Liters | Standard Deviation 0.8045 |
| Insulin Lispro + Insulin Glargine | Change From Baseline in Total Cholesterol (TC), Low-density Lipoprotein Cholesterol (LDL-c), High Density Lipoprotein (HDL-c), Triglycerides (TG) and Free Fatty Acids (FFA) at Week 10 and Week 26 | TC: Week 10, n=376,393 | 0.041 Millimoles per Liters | Standard Deviation 0.7425 |
| Insulin Lispro + Insulin Glargine | Change From Baseline in Total Cholesterol (TC), Low-density Lipoprotein Cholesterol (LDL-c), High Density Lipoprotein (HDL-c), Triglycerides (TG) and Free Fatty Acids (FFA) at Week 10 and Week 26 | HDL-c: Week 26, n=348,351 | 0.005 Millimoles per Liters | Standard Deviation 0.2138 |
| Insulin Lispro + Insulin Glargine | Change From Baseline in Total Cholesterol (TC), Low-density Lipoprotein Cholesterol (LDL-c), High Density Lipoprotein (HDL-c), Triglycerides (TG) and Free Fatty Acids (FFA) at Week 10 and Week 26 | TC: Week 26, n=348,351 | 0.073 Millimoles per Liters | Standard Deviation 0.8232 |
| Insulin Lispro + Insulin Glargine | Change From Baseline in Total Cholesterol (TC), Low-density Lipoprotein Cholesterol (LDL-c), High Density Lipoprotein (HDL-c), Triglycerides (TG) and Free Fatty Acids (FFA) at Week 10 and Week 26 | TG: Week 26, n=348,351 | -0.028 Millimoles per Liters | Standard Deviation 0.9342 |
| Insulin Lispro + Insulin Glargine | Change From Baseline in Total Cholesterol (TC), Low-density Lipoprotein Cholesterol (LDL-c), High Density Lipoprotein (HDL-c), Triglycerides (TG) and Free Fatty Acids (FFA) at Week 10 and Week 26 | HDL-c: Week 10, n=376,393 | 0.016 Millimoles per Liters | Standard Deviation 0.181 |
Secondary
Change From Baseline to Week 26 in Body Weight
Body weight was measured to the nearest 0.1 kilogram on a standard calibrated scale. Participants dressed in light indoor clothes (no coat, jacket, etc.) without shoes and with a voided bladder. The same equipment was used wherever possible. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value. Change from Baseline to Week 26 in body weight are presented. FA Population was analyzed. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.
Time frame: Baseline (Day -1) to Week 26
Population: FA Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide + Insulin Glargine | Change From Baseline to Week 26 in Body Weight | Week 5, n=382,393 | -0.95 Kilograms | Standard Error 0.102 |
| Albiglutide + Insulin Glargine | Change From Baseline to Week 26 in Body Weight | Week 18, n=365,372 | -1.96 Kilograms | Standard Error 0.177 |
| Albiglutide + Insulin Glargine | Change From Baseline to Week 26 in Body Weight | Week 10, n=379,397 | -1.71 Kilograms | Standard Error 0.133 |
| Albiglutide + Insulin Glargine | Change From Baseline to Week 26 in Body Weight | Week 26, n=349,352 | -1.95 Kilograms | Standard Error 0.207 |
| Albiglutide + Insulin Glargine | Change From Baseline to Week 26 in Body Weight | Week 4, n=368,384 | -0.55 Kilograms | Standard Error 0.091 |
| Insulin Lispro + Insulin Glargine | Change From Baseline to Week 26 in Body Weight | Week 26, n=349,352 | 2.43 Kilograms | Standard Error 0.205 |
| Insulin Lispro + Insulin Glargine | Change From Baseline to Week 26 in Body Weight | Week 4, n=368,384 | 0.66 Kilograms | Standard Error 0.091 |
| Insulin Lispro + Insulin Glargine | Change From Baseline to Week 26 in Body Weight | Week 5, n=382,393 | 0.85 Kilograms | Standard Error 0.102 |
| Insulin Lispro + Insulin Glargine | Change From Baseline to Week 26 in Body Weight | Week 10, n=379,397 | 1.46 Kilograms | Standard Error 0.131 |
| Insulin Lispro + Insulin Glargine | Change From Baseline to Week 26 in Body Weight | Week 18, n=365,372 | 2.06 Kilograms | Standard Error 0.175 |
Comparison: Week 495% CI: [-1.43, -1]
Comparison: Week 595% CI: [-2.05, -1.55]
Comparison: Week 1095% CI: [-3.51, -2.82]
Comparison: Week 1895% CI: [-4.48, -3.54]
Comparison: Week 26p-value: <0.000195% CI: [-4.93, -3.82]t-test, 2 sided
Secondary
Change From Baseline to Week 26 in FPG
FPG was measured at Baseline (Day -1) up to Week 26. FPG values for all participants at Week 26 were not collected due to an error in the protocol and were imputed with the FSG values at this time point. The imputation of the FPG at Week 26 from the FSG values was deemed acceptable from the results of the analysis of the correlation between FPG and FSG at the screening visit. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value.
Time frame: Baseline to Week 26
Population: FA Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide + Insulin Glargine | Change From Baseline to Week 26 in FPG | Week 5, n=366,388 | -1.07 Millimoles per Liter | Standard Error 0.126 |
| Albiglutide + Insulin Glargine | Change From Baseline to Week 26 in FPG | Week 26, n=345,349 | -2.01 Millimoles per Liter | Standard Error 0.12 |
| Albiglutide + Insulin Glargine | Change From Baseline to Week 26 in FPG | Week 18, n=348,353 | -1.76 Millimoles per Liter | Standard Error 0.124 |
| Albiglutide + Insulin Glargine | Change From Baseline to Week 26 in FPG | Week 4, n=356,371 | -1.30 Millimoles per Liter | Standard Error 0.119 |
| Insulin Lispro + Insulin Glargine | Change From Baseline to Week 26 in FPG | Week 18, n=348,353 | -1.23 Millimoles per Liter | Standard Error 0.124 |
| Insulin Lispro + Insulin Glargine | Change From Baseline to Week 26 in FPG | Week 5, n=366,388 | -0.88 Millimoles per Liter | Standard Error 0.125 |
| Insulin Lispro + Insulin Glargine | Change From Baseline to Week 26 in FPG | Week 4, n=356,371 | -0.76 Millimoles per Liter | Standard Error 0.118 |
| Insulin Lispro + Insulin Glargine | Change From Baseline to Week 26 in FPG | Week 26, n=345,349 | -1.46 Millimoles per Liter | Standard Error 0.121 |
Comparison: Week 495% CI: [-0.84, -0.24]
Comparison: Week 595% CI: [-0.51, 0.13]
Comparison: Week 1895% CI: [-0.85, -0.22]
Comparison: Week 26p-value: 0.000495% CI: [-0.86, -0.25]t-test, 2 sided
Secondary
Change From Baseline to Week 26 in HbA1c
HbA1c is glycosylated hemoglobin and was measured up to Week 26. The Baseline value was the last available non-missing value prior to the first dose of the randomized treatment, thus Baseline was Day -1. Change from Baseline is defined as the post-Baseline value minus the Baseline value. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.
Time frame: Baseline to Week 26
Population: FA Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide + Insulin Glargine | Change From Baseline to Week 26 in HbA1c | Week 5, n=374,392 | -0.67 Percentage of glycosylated hemoglobin | Standard Error 0.026 |
| Albiglutide + Insulin Glargine | Change From Baseline to Week 26 in HbA1c | Week 18, n=360,365 | -1.04 Percentage of glycosylated hemoglobin | Standard Error 0.038 |
| Albiglutide + Insulin Glargine | Change From Baseline to Week 26 in HbA1c | Week 10, n=376,390 | -0.88 Percentage of glycosylated hemoglobin | Standard Error 0.034 |
| Albiglutide + Insulin Glargine | Change From Baseline to Week 26 in HbA1c | Week 26, n=345,350 | -1.04 Percentage of glycosylated hemoglobin | Standard Error 0.041 |
| Albiglutide + Insulin Glargine | Change From Baseline to Week 26 in HbA1c | Week 4, n=358,375 | -0.59 Percentage of glycosylated hemoglobin | Standard Error 0.023 |
| Insulin Lispro + Insulin Glargine | Change From Baseline to Week 26 in HbA1c | Week 26, n=345,350 | -1.1 Percentage of glycosylated hemoglobin | Standard Error 0.04 |
| Insulin Lispro + Insulin Glargine | Change From Baseline to Week 26 in HbA1c | Week 4, n=358,375 | -0.47 Percentage of glycosylated hemoglobin | Standard Error 0.023 |
| Insulin Lispro + Insulin Glargine | Change From Baseline to Week 26 in HbA1c | Week 5, n=374,392 | -0.58 Percentage of glycosylated hemoglobin | Standard Error 0.025 |
| Insulin Lispro + Insulin Glargine | Change From Baseline to Week 26 in HbA1c | Week 10, n=376,390 | -0.96 Percentage of glycosylated hemoglobin | Standard Error 0.033 |
| Insulin Lispro + Insulin Glargine | Change From Baseline to Week 26 in HbA1c | Week 18, n=360,365 | -1.14 Percentage of glycosylated hemoglobin | Standard Error 0.038 |
Comparison: Week 4p-value: <0.000195% CI: [-0.18, -0.07]t-test, 1 sided
Comparison: Week 5p-value: <0.000195% CI: [-0.15, -0.02]t-test, 1 sided
Comparison: Week 10p-value: <0.000195% CI: [-0.01, 0.17]t-test, 1 sided
Comparison: Week 18p-value: <0.000195% CI: [0.01, 0.21]t-test, 1 sided
Comparison: Week 26p-value: <0.000195% CI: [-0.05, 0.17]t-test, 1 sided
Secondary
Mean Albumin at Week 0 and Week 26
Urine samples were collected for analysis of albumin. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Mean albumin at Week 0 and Week 26 are presented.
Time frame: Week 0 and Week 26
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide + Insulin Glargine | Mean Albumin at Week 0 and Week 26 | Week 0, n=394,405 | 127.7 Milligrams per Liter | Standard Deviation 428.46 |
| Albiglutide + Insulin Glargine | Mean Albumin at Week 0 and Week 26 | Week 26, n=348,345 | 110.5 Milligrams per Liter | Standard Deviation 375.41 |
| Insulin Lispro + Insulin Glargine | Mean Albumin at Week 0 and Week 26 | Week 0, n=394,405 | 108.2 Milligrams per Liter | Standard Deviation 301.88 |
| Insulin Lispro + Insulin Glargine | Mean Albumin at Week 0 and Week 26 | Week 26, n=348,345 | 146.3 Milligrams per Liter | Standard Deviation 628.73 |
Secondary
Mean Creatinine at Week 0 and Week 26
Urine samples were collected for analysis of creatinine. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Mean creatinine at Week 0 and Week 26 are presented.
Time frame: Week 0 and Week 26
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide + Insulin Glargine | Mean Creatinine at Week 0 and Week 26 | Week 0, n=395,406 | 10646.3 Micromoles per Liter | Standard Deviation 5190.43 |
| Albiglutide + Insulin Glargine | Mean Creatinine at Week 0 and Week 26 | Week 26, n=350,345 | 11364.6 Micromoles per Liter | Standard Deviation 5998.72 |
| Insulin Lispro + Insulin Glargine | Mean Creatinine at Week 0 and Week 26 | Week 0, n=395,406 | 10663.8 Micromoles per Liter | Standard Deviation 5639.54 |
| Insulin Lispro + Insulin Glargine | Mean Creatinine at Week 0 and Week 26 | Week 26, n=350,345 | 11394.2 Micromoles per Liter | Standard Deviation 5663.72 |
Secondary
Mean Specific Gravity at Week 0 and Week 26
Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The concentration of the excreted molecules determines the urine's specific gravity. A urinary specific gravity measurement is a routine part of urinalysis. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.
Time frame: Week 0 and Week 26
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide + Insulin Glargine | Mean Specific Gravity at Week 0 and Week 26 | Week 0, n=388,402 | 1.0182 Ratio | Standard Deviation 0.00599 |
| Albiglutide + Insulin Glargine | Mean Specific Gravity at Week 0 and Week 26 | Week 26, n=347,343 | 1.0180 Ratio | Standard Deviation 0.00627 |
| Insulin Lispro + Insulin Glargine | Mean Specific Gravity at Week 0 and Week 26 | Week 0, n=388,402 | 1.0180 Ratio | Standard Deviation 0.00588 |
| Insulin Lispro + Insulin Glargine | Mean Specific Gravity at Week 0 and Week 26 | Week 26, n=347,343 | 1.0186 Ratio | Standard Deviation 0.00588 |
Secondary
Mean Urine Albumin/Creatinine Ratio at Week 0 and Week 26
Urine samples were collected for analysis of albumin/creatinine ratio. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Mean urine albumin/creatinine ratio at Week 0 and Week 26 are presented.
Time frame: Week 0 and Week 26
Population: Safety Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide + Insulin Glargine | Mean Urine Albumin/Creatinine Ratio at Week 0 and Week 26 | Week 0, n=369,376 | 14.40 Grams per mole | Standard Deviation 49.884 |
| Albiglutide + Insulin Glargine | Mean Urine Albumin/Creatinine Ratio at Week 0 and Week 26 | Week 26, n=317,324 | 10.37 Grams per mole | Standard Deviation 32.992 |
| Insulin Lispro + Insulin Glargine | Mean Urine Albumin/Creatinine Ratio at Week 0 and Week 26 | Week 0, n=369,376 | 11.57 Grams per mole | Standard Deviation 31.089 |
| Insulin Lispro + Insulin Glargine | Mean Urine Albumin/Creatinine Ratio at Week 0 and Week 26 | Week 26, n=317,324 | 11.55 Grams per mole | Standard Deviation 31.975 |
Secondary
Number of Participants Achieving a HbA1c <6.5% at Week 26
Number of participants achieving a HbA1c \<6.5% at Week 26 are presented.
Time frame: Week 26
Population: FA Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants Achieving a HbA1c <6.5% at Week 26 | 147 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Achieving a HbA1c <6.5% at Week 26 | 169 Participants |
p-value: 0.229895% CI: [0.63, 1.17]Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving a HbA1c <6.5% up to Week 26
Number of participants achieving a HbA1c \<6.5% up to Week 26 are presented.
Time frame: Up to Week 26
Population: FA Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants Achieving a HbA1c <6.5% up to Week 26 | Week 5 | 63 Participants |
| Albiglutide + Insulin Glargine | Number of Participants Achieving a HbA1c <6.5% up to Week 26 | Week 18 | 150 Participants |
| Albiglutide + Insulin Glargine | Number of Participants Achieving a HbA1c <6.5% up to Week 26 | Week 10 | 116 Participants |
| Albiglutide + Insulin Glargine | Number of Participants Achieving a HbA1c <6.5% up to Week 26 | Week 26 | 147 Participants |
| Albiglutide + Insulin Glargine | Number of Participants Achieving a HbA1c <6.5% up to Week 26 | Week 4 | 39 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Achieving a HbA1c <6.5% up to Week 26 | Week 26 | 169 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Achieving a HbA1c <6.5% up to Week 26 | Week 4 | 33 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Achieving a HbA1c <6.5% up to Week 26 | Week 5 | 62 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Achieving a HbA1c <6.5% up to Week 26 | Week 10 | 140 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Achieving a HbA1c <6.5% up to Week 26 | Week 18 | 178 Participants |
Comparison: Week 4p-value: 0.214395% CI: [0.78, 2.23]Cochran-Mantel-Haenszel
Comparison: Week 5p-value: 0.470395% CI: [0.8, 1.91]Cochran-Mantel-Haenszel
Comparison: Week 10p-value: 0.213995% CI: [0.58, 1.14]Cochran-Mantel-Haenszel
Comparison: Week 18p-value: 0.07995% CI: [0.59, 1.11]Cochran-Mantel-Haenszel
Comparison: Week 26p-value: 0.229895% CI: [0.63, 1.17]Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving HbA1c <7.0% at Week 26
HbA1c is glycosylated hemoglobin. Number of participants achieving a HbA1c \<7.0% at Week 26 are presented.
Time frame: Week 26
Population: FA Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants Achieving HbA1c <7.0% at Week 26 | 244 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Achieving HbA1c <7.0% at Week 26 | 255 Participants |
p-value: 0.702695% CI: [0.71, 1.31]Cochran-Mantel-Haenszel
Secondary
Number of Participants Achieving HbA1c <7.0% up to Week 26
HbA1c is glycosylated hemoglobin. Number of participants achieving a HbA1c \<7.0% up to Week 26 are presented.
Time frame: Up to Week 26
Population: FA Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants Achieving HbA1c <7.0% up to Week 26 | Week 5 | 157 Participants |
| Albiglutide + Insulin Glargine | Number of Participants Achieving HbA1c <7.0% up to Week 26 | Week 10 | 220 Participants |
| Albiglutide + Insulin Glargine | Number of Participants Achieving HbA1c <7.0% up to Week 26 | Week 18 | 251 Participants |
| Albiglutide + Insulin Glargine | Number of Participants Achieving HbA1c <7.0% up to Week 26 | Week 26 | 244 Participants |
| Albiglutide + Insulin Glargine | Number of Participants Achieving HbA1c <7.0% up to Week 26 | Week 4 | 142 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Achieving HbA1c <7.0% up to Week 26 | Week 26 | 255 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Achieving HbA1c <7.0% up to Week 26 | Week 4 | 139 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Achieving HbA1c <7.0% up to Week 26 | Week 5 | 182 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Achieving HbA1c <7.0% up to Week 26 | Week 18 | 281 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Achieving HbA1c <7.0% up to Week 26 | Week 10 | 261 Participants |
Comparison: Week 4p-value: 0.288395% CI: [0.84, 1.64]Cochran-Mantel-Haenszel
Comparison: Week 5p-value: 0.303495% CI: [0.59, 1.15]Cochran-Mantel-Haenszel
Comparison: Week 10p-value: 0.015195% CI: [0.52, 0.98]Cochran-Mantel-Haenszel
Comparison: Week 18p-value: 0.051895% CI: [0.54, 1.03]Cochran-Mantel-Haenszel
Comparison: Week 26p-value: 0.702695% CI: [0.71, 1.31]Cochran-Mantel-Haenszel
Secondary
Number of Participants Meeting Prespecified Criteria for Severe, Persistent Hyperglycemia up to Week 26
Meeting prespecified criteria for severe, persistent hyperglycemia was defined operationally as being withdrawn due to lack of efficacy as recorded on the Treatment Discontinuation and Study Conclusion electronic case report form pages. Number of participants meeting prespecified criteria for severe, persistent hyperglycemia up to Week 26 are presented.
Time frame: Up to Week 26
Population: FA Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants Meeting Prespecified Criteria for Severe, Persistent Hyperglycemia up to Week 26 | >4 to <=5 Weeks | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants Meeting Prespecified Criteria for Severe, Persistent Hyperglycemia up to Week 26 | >10 to <=18 Weeks | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants Meeting Prespecified Criteria for Severe, Persistent Hyperglycemia up to Week 26 | >5 to <=10 Weeks | 2 Participants |
| Albiglutide + Insulin Glargine | Number of Participants Meeting Prespecified Criteria for Severe, Persistent Hyperglycemia up to Week 26 | >18 to <=26 Weeks | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants Meeting Prespecified Criteria for Severe, Persistent Hyperglycemia up to Week 26 | 0 to <=4 Weeks | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Meeting Prespecified Criteria for Severe, Persistent Hyperglycemia up to Week 26 | >18 to <=26 Weeks | 2 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Meeting Prespecified Criteria for Severe, Persistent Hyperglycemia up to Week 26 | 0 to <=4 Weeks | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Meeting Prespecified Criteria for Severe, Persistent Hyperglycemia up to Week 26 | >4 to <=5 Weeks | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Meeting Prespecified Criteria for Severe, Persistent Hyperglycemia up to Week 26 | >5 to <=10 Weeks | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Meeting Prespecified Criteria for Severe, Persistent Hyperglycemia up to Week 26 | >10 to <=18 Weeks | 1 Participants |
Secondary
Number of Participants Treated With Once-weekly Albiglutide That Were Able to Discontinue Insulin Lispro at Week 4 and Did Not Meet Prespecified Criteria for Severe, Persistent Hyperglycemia Through Week 26
Participants who did not meet prespecified criteria for severe, persistent hyperglycemia through Week 26 were those participants treated with once-weekly albiglutide that were able to replace prandial insulin without lispro re-introduction through Week 26. Number of participants treated with once-weekly albiglutide that were able to discontinue insulin lispro at Week 4 and did not meet prespecified criteria for severe, persistent hyperglycemia through Week 26 have been presented.
Time frame: Up to Week 26
Population: FA Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants Treated With Once-weekly Albiglutide That Were Able to Discontinue Insulin Lispro at Week 4 and Did Not Meet Prespecified Criteria for Severe, Persistent Hyperglycemia Through Week 26 | 218 Participants |
Secondary
Number of Participants Who Met Prespecified Criteria for Severe, Persistent Hyperglycemia at Week 26
Meeting prespecified criteria for severe, persistent hyperglycemia was defined operationally as being withdrawn due to lack of efficacy as recorded on the Treatment Discontinuation and Study Conclusion electronic case report form pages. Number of participants who met prespecified criteria for severe, persistent hyperglycemia at Week 26 are presented.
Time frame: Week 26
Population: FA Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants Who Met Prespecified Criteria for Severe, Persistent Hyperglycemia at Week 26 | 3 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants Who Met Prespecified Criteria for Severe, Persistent Hyperglycemia at Week 26 | 3 Participants |
p-value: 0.829295% CI: [0.24, 4.77]Cochran-Mantel-Haenszel
Secondary
Number of Participants With Clinical Chemistry Values of Clinical Concern
Clinical chemistry parameters and their potential clinical concern values were: albumin (\>5 g/L above ULN or below LLN), alkaline phosphatase(\>3 x ULN), alanine aminotransferase (\>3 x ULN), aspartate aminotransferase (\>3 x ULN), carbon dioxide content (\<16 millimoles per Liter \[mmol/L\] and \> 40 mmol/L), blood urea nitrogen (\>2 x ULN), calcium (\<1.8 mmol/L and \>3.0 mmol/L), chloride (none), creatinine (\>159 micromoles/Liter), direct bilirubin (\>1.35 x ULN), gamma glutamyl transferase (\>3 x ULN), glucose (fasting) (\<3 mmol/L and \>22 mmol/L), magnesium (\<0.411 mmol/L and \>1.644 mmol/L), phosphate (\>0.323 mmol/L above ULN or below LLN), potassium (\>0.5 mmol/L below LLN and \>1.0 mmol/L above ULN), sodium (\>5 mmol/L above ULN or below LLN), triglycerides (\> 9.04 mmol/L), total bilirubin (\>1.5 x ULN), total protein (\>15 g/L above ULN or below LLN) and uric acid (\>654 umol/L). Only those parameters for which at least one value of potential clinical concern was reported are summarized.
Time frame: Up to 30 weeks
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Potassium: >1.0 mmol/L above ULN, n=394,407 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Carbon Dioxide: <16 mmol/L, n=394,407 | 5 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Protein: >15 g/L below LLN, n=394,407 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Fasting Serum Glucose: >22 mmol/L, n= 394,405 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Protein: >15 g/L above ULN, n=394,407 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Carbon Dioxide: >40 mmol/L, n=394,407 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Sodium: >5 mmol/L below LLN, n=394,407 | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Albumin: >5 g/L above ULN, n=394,407 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Sodium: >5 mmol/L above ULN, n=394,407 | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Magnesium: <0.411 mmol/L, n=394,407 | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Triglycerides: >9.04 mmol/L, n=393,405 | 7 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Fasting Plasma Glucose: >22 mmol/L, n= 388,406 | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Urate: >654 μmol/L, n=394,407 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Magnesium: >1.644 mmol/L, n=394,407 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Urea: >2 x ULN, n=394,407 | 2 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Calcium: <1.8 mmol/L, n=394,407 | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Alanine Aminotransferase: >3 x ULN, n=396,410 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Phosphate: >0.323 mmol/L below LLN, n=394,407 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Alkaline Phosphatase: >3 x ULN, n=396,410 | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Fasting Plasma Glucose: <3 mmol/L, n= 388,406 | 9 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Aspartate Aminotransferase: >3 x ULN, n=396,410 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Phosphate: >0.323 mmol/L above ULN, n=394,407 | 2 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Bilirubin: >1.5 x ULN, n=396,410 | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Calcium: >3.0 mmol/L, n=394,407 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Creatinine: >159 μmol/L, n=396,410 | 20 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Potassium: >0.5 mmol/L below LLN, n=394,407 | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Direct Bilirubin: >1.35 x ULN, n=396,410 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Albumin: >5 g/L below LLN, n=394,407 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Gamma Glutamyl Transferase: >3 x ULN, n=396,410 | 14 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Fasting Serum Glucose: <3 mmol/L, n= 394,405 | 12 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Gamma Glutamyl Transferase: >3 x ULN, n=396,410 | 14 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Fasting Serum Glucose: <3 mmol/L, n= 394,405 | 16 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Fasting Serum Glucose: >22 mmol/L, n= 394,405 | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Fasting Plasma Glucose: <3 mmol/L, n= 388,406 | 14 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Fasting Plasma Glucose: >22 mmol/L, n= 388,406 | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Albumin: >5 g/L below LLN, n=394,407 | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Albumin: >5 g/L above ULN, n=394,407 | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Calcium: <1.8 mmol/L, n=394,407 | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Calcium: >3.0 mmol/L, n=394,407 | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Carbon Dioxide: <16 mmol/L, n=394,407 | 8 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Carbon Dioxide: >40 mmol/L, n=394,407 | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Magnesium: <0.411 mmol/L, n=394,407 | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Magnesium: >1.644 mmol/L, n=394,407 | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Phosphate: >0.323 mmol/L below LLN, n=394,407 | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Phosphate: >0.323 mmol/L above ULN, n=394,407 | 4 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Potassium: >0.5 mmol/L below LLN, n=394,407 | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Potassium: >1.0 mmol/L above ULN, n=394,407 | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Protein: >15 g/L below LLN, n=394,407 | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Protein: >15 g/L above ULN, n=394,407 | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Sodium: >5 mmol/L below LLN, n=394,407 | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Sodium: >5 mmol/L above ULN, n=394,407 | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Triglycerides: >9.04 mmol/L, n=393,405 | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Urate: >654 μmol/L, n=394,407 | 2 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Urea: >2 x ULN, n=394,407 | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Alanine Aminotransferase: >3 x ULN, n=396,410 | 5 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Alkaline Phosphatase: >3 x ULN, n=396,410 | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Aspartate Aminotransferase: >3 x ULN, n=396,410 | 2 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Bilirubin: >1.5 x ULN, n=396,410 | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Creatinine: >159 μmol/L, n=396,410 | 16 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinical Chemistry Values of Clinical Concern | Direct Bilirubin: >1.35 x ULN, n=396,410 | 1 Participants |
Secondary
Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Parameters
A single 12-lead ECG recordings were performed in a participant in semi recumbent position for 10 to 15 minutes before obtaining the ECG. Any clinically significant favorable and unfavorable findings are reported.
Time frame: Up to 30 weeks
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Parameters | Clinically Significant Change: Favorable | 18 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Parameters | Clinically Significant Change: Unfavorable | 4 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Parameters | Clinically Significant Change: Favorable | 9 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Clinically Significant Change in Electrocardiogram (ECG) Parameters | Clinically Significant Change: Unfavorable | 5 Participants |
Secondary
Number of Participants With Daytime and Nocturnal Hypoglycemia
Daytime hypoglycemia was defined as hypoglycemic events with an onset between 06:00 hours and 00:00 hours (inclusive), and nocturnal hypoglycemia (in total and by category), defined as hypoglycemic events with an onset between 00:01 hours and 05:59 hours (inclusive). Number of participants with daytime and nocturnal hypoglycemia (in total and by category) are presented.
Time frame: Up to Week 26
Population: Safety Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Any (Total) Daytime Hypoglycemic Event | 288 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Any (Total) Nocturnal Hypoglycemic Event | 155 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Severe Daytime Hypoglycemic Event | 6 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Severe Nocturnal Hypoglycemic Event | 4 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Documented Symptomatic Daytime Hypoglycemic event | 187 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Documented Symptomatic Nocturnal Hypoglycemia | 101 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Asymptomatic Daytime Hypoglycemic event | 217 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Asymptomatic Nocturnal Hypoglycemic event | 77 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Probably Symptomatic Daytime Hypoglycemic event | 22 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Probably Symptomatic Nocturnal Hypoglycemic event | 7 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Pseudohypoglycemia Daytime Hypoglycemic event | 36 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Pseudohypoglycemia Nocturnal Hypoglycemic event | 17 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Missing Daytime Hypoglycemic Event | 9 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Mising Nocturnal Hypoglycemic Event | 2 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Pseudohypoglycemia Daytime Hypoglycemic event | 70 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Any (Total) Daytime Hypoglycemic Event | 356 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Asymptomatic Nocturnal Hypoglycemic event | 106 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Any (Total) Nocturnal Hypoglycemic Event | 225 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Missing Daytime Hypoglycemic Event | 11 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Severe Daytime Hypoglycemic Event | 14 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Probably Symptomatic Daytime Hypoglycemic event | 44 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Severe Nocturnal Hypoglycemic Event | 6 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Pseudohypoglycemia Nocturnal Hypoglycemic event | 34 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Documented Symptomatic Daytime Hypoglycemic event | 293 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Probably Symptomatic Nocturnal Hypoglycemic event | 21 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Documented Symptomatic Nocturnal Hypoglycemia | 152 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Mising Nocturnal Hypoglycemic Event | 4 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Daytime and Nocturnal Hypoglycemia | Asymptomatic Daytime Hypoglycemic event | 281 Participants |
Secondary
Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26
Urine samples were collected for analysis of erythrocyte count. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Number of participants with different number of erythrocytes in urine at Week 0 and Week 26 are presented.
Time frame: Week 0 and Week 26
Population: Safety Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | >100; Week 26, n=166,144 | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | None Seen; Week 0, n=171,187 | 119 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 0 to 1; Week 0, n=171,187 | 34 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 1 to 3; Week 0, n=171,187 | 9 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 3 to 5; Week 0, n=171,187 | 3 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 5 to 10; Week 0, n=171,187 | 2 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 10 to 15; Week 0, n=171,187 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 15 to 25; Week 0, n=171,187 | 2 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 50 to 100; Week 0, n=171,187 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | >100; Week 0, n=171,187 | 2 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | None Seen; Week 26, n=166,144 | 98 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 0 to 1; Week 26, n=166,144 | 48 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 1 to 3; Week 26, n=166,144 | 8 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 3 to 5; Week 26, n=166,144 | 4 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 5 to 10; Week 26, n=166,144 | 4 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 25 to 50; Week 26, n=166,144 | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 50 to 100; Week 26, n=166,144 | 2 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 3 to 5; Week 26, n=166,144 | 3 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | >100; Week 0, n=171,187 | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | None Seen; Week 0, n=171,187 | 101 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | >100; Week 26, n=166,144 | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 0 to 1; Week 0, n=171,187 | 51 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | None Seen; Week 26, n=166,144 | 79 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 1 to 3; Week 0, n=171,187 | 14 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 5 to 10; Week 26, n=166,144 | 4 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 3 to 5; Week 0, n=171,187 | 12 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 0 to 1; Week 26, n=166,144 | 36 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 5 to 10; Week 0, n=171,187 | 4 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 50 to 100; Week 26, n=166,144 | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 10 to 15; Week 0, n=171,187 | 2 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 1 to 3; Week 26, n=166,144 | 19 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 15 to 25; Week 0, n=171,187 | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 25 to 50; Week 26, n=166,144 | 2 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Erythrocytes in Urine at Week 0 and Week 26 | 50 to 100; Week 0, n=171,187 | 1 Participants |
Secondary
Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26
Urine samples were collected for analysis of leukocyte count. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles. Number of participants with different number of leukocytes in urine at Week 0 and Week 26 are presented.
Time frame: Week 0 and Week 26
Population: Safety Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | None Seen; Week 0, n=171,187 | 69 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 0 to 1; Week 0, n=171,187 | 27 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 1 to 3; Week 0, n=171,187 | 20 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 3 to 5; Week 0, n=171,187 | 16 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 5 to 10; Week 0, n=171,187 | 17 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 10 to 15; Week 0, n=171,187 | 7 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 15 to 25; Week 0, n=171,187 | 5 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 25 to 50; Week 0, n=171,187 | 5 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 50 to 100; Week 0, n=171,187 | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | >100; Week 0, n=171,187 | 4 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | Innumerable; Week 0, n=171,187 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | None Seen; Week 26, n=166,144 | 65 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 0 to 1; Week 26, n=166,144 | 25 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 1 to 3; Week 26, n=166,144 | 22 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 3 to 5; Week 26, n=166,144 | 10 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 5 to 10; Week 26, n=166,144 | 22 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 10 to 15; Week 26, n=166,144 | 8 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 15 to 25; Week 26, n=166,144 | 3 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 20 to 50; Week 26, n=166,144 | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 25 to 50; Week 26, n=166,144 | 5 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 50 to 100; Week 26, n=166,144 | 5 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | >100; Week 26, n=166,144 | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | Innumerable; Week 26, n=166,144 | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | None Seen; Week 26, n=166,144 | 44 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | None Seen; Week 0, n=171,187 | 67 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 15 to 25; Week 26, n=166,144 | 3 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 0 to 1; Week 0, n=171,187 | 31 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 0 to 1; Week 26, n=166,144 | 29 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 1 to 3; Week 0, n=171,187 | 18 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 50 to 100; Week 26, n=166,144 | 5 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 3 to 5; Week 0, n=171,187 | 13 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 1 to 3; Week 26, n=166,144 | 20 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 5 to 10; Week 0, n=171,187 | 19 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 20 to 50; Week 26, n=166,144 | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 10 to 15; Week 0, n=171,187 | 6 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 3 to 5; Week 26, n=166,144 | 15 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 15 to 25; Week 0, n=171,187 | 11 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | Innumerable; Week 26, n=166,144 | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 25 to 50; Week 0, n=171,187 | 11 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 5 to 10; Week 26, n=166,144 | 14 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 50 to 100; Week 0, n=171,187 | 7 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 25 to 50; Week 26, n=166,144 | 6 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | >100; Week 0, n=171,187 | 3 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | 10 to 15; Week 26, n=166,144 | 5 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | Innumerable; Week 0, n=171,187 | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Number of Leukocytes in Urine at Week 0 and Week 26 | >100; Week 26, n=166,144 | 1 Participants |
Secondary
Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26
Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. A pH of 7 is neutral. A pH less than 7 is acidic, and a pH greater than 7 is basic. Normal urine has a slightly acid pH (5.0 - 6.0). Safety Population was analyzed. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.
Time frame: Week 0 and Week 26
Population: Safety Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=5.5; Week 0, n=388,402 | 132 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=5.5; Week 26, n=347,343 | 107 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=7.5; Week 0, n=388,402 | 13 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=6; Week 26, n=347,343 | 69 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=6.5; Week 0, n=388,402 | 29 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=6.5; Week 26, n=347,343 | 42 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=8; Week 0, n=388,402 | 6 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=7; Week 26, n=347,343 | 19 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=6; Week 0, n=388,402 | 86 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=7.5; Week 26, n=347,343 | 17 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=8.5; Week 0, n=388,402 | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=8; Week 26, n=347,343 | 7 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=7; Week 0, n=388,402 | 29 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=8.5; Week 26, n=347,343 | 5 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=5; Week 26, n=347,343 | 80 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH>9; Week 26, n=347,343 | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=5; Week 0, n=388,402 | 92 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH>9; Week 26, n=347,343 | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=5; Week 0, n=388,402 | 107 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=5.5; Week 0, n=388,402 | 132 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=6; Week 0, n=388,402 | 77 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=6.5; Week 0, n=388,402 | 43 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=7; Week 0, n=388,402 | 24 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=7.5; Week 0, n=388,402 | 11 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=8; Week 0, n=388,402 | 7 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=8.5; Week 0, n=388,402 | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=5; Week 26, n=347,343 | 100 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=5.5; Week 26, n=347,343 | 104 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=6; Week 26, n=347,343 | 70 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=6.5; Week 26, n=347,343 | 23 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=7; Week 26, n=347,343 | 23 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=7.5; Week 26, n=347,343 | 18 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=8; Week 26, n=347,343 | 5 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Different Values of Potential of Hydrogen (pH) at Week 0 and Week 26 | pH=8.5; Week 26, n=347,343 | 0 Participants |
Secondary
Number of Participants With Hematology Values of Clinical Concern
Hematology parameters included basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, monocytes, neutrophils, neutrophil bands, platelets, red blood cell (RBC) count, segmented neutrophils and white blood cell (WBC) count. The potential clinical concern values were: Hematocrit \>0.05 below lower limit of normal (LLN) and \>0.04 above upper limit of normal (ULN), hemoglobin: \>20 grams cells per Liter (g/L) below LLN and \>10 g/L above ULN, lymphocytes: \<0.5 x LLN, neutrophils: \<1 giga cells per liter (GI/L), platelets: \<80 GI/L and \>500 GI/L, segmented neutrophils: \<0.5 x LLN, RBC count: \>1 GI/L below LLN and \>5 GI/L above ULN and none for basophils, eosinophils, monocytes, neutrophil bands and RBC count. Only those parameters for which at least one value of potential clinical concern was reported are summarized.
Time frame: Up to 30 weeks
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Hematocrit: >0.05 (fraction) below LLN | 5 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Hematocrit: >0.04 (fraction) above ULN | 9 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Hemoglobin: >20 g/L below LLN | 9 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Hemoglobin: >10 g/L above ULN | 2 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Leukocytes: >1 GI/L below LLN | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Leukocytes: >5 GI/L above ULN | 4 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Neutrophils: <1 GI/L | 2 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Neutrophils, Segmented: <0.5 x LLN | 2 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Platelets: <80 GI/L | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Platelets: >500 GI/L | 3 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Neutrophils, Segmented: <0.5 x LLN | 3 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Hematocrit: >0.05 (fraction) below LLN | 6 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Leukocytes: >5 GI/L above ULN | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Hematocrit: >0.04 (fraction) above ULN | 12 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Platelets: >500 GI/L | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Hemoglobin: >20 g/L below LLN | 9 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Neutrophils: <1 GI/L | 3 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Hemoglobin: >10 g/L above ULN | 3 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Platelets: <80 GI/L | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hematology Values of Clinical Concern | Leukocytes: >1 GI/L below LLN | 1 Participants |
Secondary
Number of Participants With Hypoglycemia With Blood Glucose <56 Milligrams Per Deciliter (mg/dL) (<3.1 Millimoles Per Liter [mmol/L]), Regardless of Symptoms
Number of participants with hypoglycemia with blood glucose \<56 mg/dL (\<3.1 mmol/L), regardless of symptoms are presented.
Time frame: Up to Week 26
Population: Safety Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants With Hypoglycemia With Blood Glucose <56 Milligrams Per Deciliter (mg/dL) (<3.1 Millimoles Per Liter [mmol/L]), Regardless of Symptoms | 141 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hypoglycemia With Blood Glucose <56 Milligrams Per Deciliter (mg/dL) (<3.1 Millimoles Per Liter [mmol/L]), Regardless of Symptoms | 239 Participants |
Secondary
Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria)
The American Diabetes Association has categorized hypoglycemic events as follows: Severe, documented symptomatic, asymptomatic, probably symptomatic and pseudohypoglycemia. Number of participants with hypoglycemic events in total are also presented.
Time frame: Up to Week 26
Population: Safety Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria) | Asymptomatic | 230 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria) | Pseudohypoglycemia | 45 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria) | Documented Symptomatic | 203 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria) | Missing | 9 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria) | Probably Symptomatic | 29 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria) | Total | 305 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria) | Severe | 9 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria) | Total | 361 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria) | Severe | 22 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria) | Documented Symptomatic | 299 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria) | Asymptomatic | 293 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria) | Probably Symptomatic | 52 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria) | Pseudohypoglycemia | 83 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Hypoglycemic Events (in Total and by Each Category as Defined by the American Diabetes Association Criteria) | Missing | 13 Participants |
Secondary
Number of Participants With On-therapy Adverse Events (AE) and Serious AE (SAE), and AE Leading to Discontinuation of Randomized Study Medication
AE is any untoward medical occurrence in a participant, temporally associated with use of medicinal product (MP), whether or not considered related to MP. AE can be any unfavorable, unintended sign (also an abnormal laboratory finding), symptom, or disease (new/exacerbated) temporally associated with use of MP. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability, or is a congenital anomaly/birth defect or is medically significant or all events of possible drug induced liver injury with hyperbilirubinemia. Safety Population: All participants who received at least 1 dose of randomized study medication. A participant randomized to Albiglutide + Insulin glargine by mistake received Insulin Lispro + Insulin Glargine instead. Since this participant received actual treatment as Insulin Lispro + Insulin Glargine, was summarized as such in Safety Population.
Time frame: Up to Week 26
Population: Safety Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants With On-therapy Adverse Events (AE) and Serious AE (SAE), and AE Leading to Discontinuation of Randomized Study Medication | AE | 261 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With On-therapy Adverse Events (AE) and Serious AE (SAE), and AE Leading to Discontinuation of Randomized Study Medication | SAE | 23 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With On-therapy Adverse Events (AE) and Serious AE (SAE), and AE Leading to Discontinuation of Randomized Study Medication | AE leading to study medication discontinuation | 12 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With On-therapy Adverse Events (AE) and Serious AE (SAE), and AE Leading to Discontinuation of Randomized Study Medication | AE | 254 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With On-therapy Adverse Events (AE) and Serious AE (SAE), and AE Leading to Discontinuation of Randomized Study Medication | SAE | 31 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With On-therapy Adverse Events (AE) and Serious AE (SAE), and AE Leading to Discontinuation of Randomized Study Medication | AE leading to study medication discontinuation | 6 Participants |
Secondary
Number of Participants With Other AE of Special Interest
AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with use of a MP, whether or not considered related to MP. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with use of MP. AE of special interest included hypoglycemic events, cardiovascular events, gastrointestinal events, injection site reactions, potential systemic allergic reactions, pancreatitis, pancreatic cancer, malignant neoplasms following treatment with insulin, diabetic retinopathy events, appendicitis, liver events, pneumonia, and atrial fibrillation/flutter.
Time frame: Up to Week 26
Population: Safety Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants With Other AE of Special Interest | Gastrointestinal Events | 102 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Other AE of Special Interest | Malignant Neoplasm | 2 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Other AE of Special Interest | Systemic Allergic Reactions | 3 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Other AE of Special Interest | Diabetic Retinopathy | 4 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Other AE of Special Interest | Cardiovascular Events | 7 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Other AE of Special Interest | Appendicitis | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Other AE of Special Interest | Pancreatitis | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Other AE of Special Interest | Liver Events | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Other AE of Special Interest | Injection Site Reactions | 8 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Other AE of Special Interest | Pneumonia | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Other AE of Special Interest | Pancreatic cancer | 0 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Other AE of Special Interest | Atrial Fibrillation/Flutter | 4 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Other AE of Special Interest | Hypoglycemic Events | 305 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Other AE of Special Interest | Atrial Fibrillation/Flutter | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Other AE of Special Interest | Hypoglycemic Events | 361 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Other AE of Special Interest | Cardiovascular Events | 9 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Other AE of Special Interest | Gastrointestinal Events | 53 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Other AE of Special Interest | Injection Site Reactions | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Other AE of Special Interest | Systemic Allergic Reactions | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Other AE of Special Interest | Pancreatitis | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Other AE of Special Interest | Pancreatic cancer | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Other AE of Special Interest | Malignant Neoplasm | 2 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Other AE of Special Interest | Diabetic Retinopathy | 17 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Other AE of Special Interest | Appendicitis | 0 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Other AE of Special Interest | Liver Events | 2 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Other AE of Special Interest | Pneumonia | 3 Participants |
Secondary
Number of Participants With Vital Signs of Clinical Concern
Vital signs included systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse rate values. Assessment of vitals were performed with the participant in a semi recumbent or seated position having rested in this position for at least 5 minutes before each reading. The potential clinical concern values were: SBP: \<100 millimeters of mercury (mmHg) and \>170 mmHg, DBP: \<50 mmHg and \>110 mmHg and pulse rate: \<50 beats per minute (bpm) and \> 120 bpm. Number of participants with vital signs of clinical concern are presented.
Time frame: Up to 30 weeks
Population: Safety Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Number of Participants With Vital Signs of Clinical Concern | Pulse Rate: < 50 bpm | 4 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Vital Signs of Clinical Concern | SBP: > 170 mmHg | 27 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Vital Signs of Clinical Concern | DBP: < 50 mmHg | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Vital Signs of Clinical Concern | DBP: > 110 mmHg | 1 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Vital Signs of Clinical Concern | Pulse Rate: > 120 bpm | 3 Participants |
| Albiglutide + Insulin Glargine | Number of Participants With Vital Signs of Clinical Concern | SBP: < 100 mmHg | 21 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Vital Signs of Clinical Concern | Pulse Rate: > 120 bpm | 1 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Vital Signs of Clinical Concern | SBP: < 100 mmHg | 20 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Vital Signs of Clinical Concern | DBP: > 110 mmHg | 5 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Vital Signs of Clinical Concern | SBP: > 170 mmHg | 30 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Vital Signs of Clinical Concern | Pulse Rate: < 50 bpm | 9 Participants |
| Insulin Lispro + Insulin Glargine | Number of Participants With Vital Signs of Clinical Concern | DBP: < 50 mmHg | 4 Participants |
Secondary
Percentage of Participants Achieving HbA1c <7.0% Without Severe or Documented Symptomatic Hypoglycemia at Week 26
Percentage of participants achieving HbA1c \<7.0% without severe or documented symptomatic hypoglycemia are presented.
Time frame: Week 26
Population: FA Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albiglutide + Insulin Glargine | Percentage of Participants Achieving HbA1c <7.0% Without Severe or Documented Symptomatic Hypoglycemia at Week 26 | 21.1 Percentage of participants |
| Insulin Lispro + Insulin Glargine | Percentage of Participants Achieving HbA1c <7.0% Without Severe or Documented Symptomatic Hypoglycemia at Week 26 | 9.5 Percentage of participants |
p-value: <0.000195% CI: [1.54, 3.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving HbA1c <7.0% Without Weight Gain and Without Severe or Documented Hypoglycemia at Week 26
Percentage of participants achieving HbA1c \<7.0% without weight gain and without severe or documented hypoglycemia are presented.
Time frame: Week 26
Population: FA Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albiglutide + Insulin Glargine | Percentage of Participants Achieving HbA1c <7.0% Without Weight Gain and Without Severe or Documented Hypoglycemia at Week 26 | 15.9 Percentage of participants |
| Insulin Lispro + Insulin Glargine | Percentage of Participants Achieving HbA1c <7.0% Without Weight Gain and Without Severe or Documented Hypoglycemia at Week 26 | 3.9 Percentage of participants |
p-value: <0.000195% CI: [2.21, 6.48]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants Achieving HbA1c <7.0% Without Weight Gain at Week 26
Percentage of participants achieving HbA1c \<7.0% without weight gain are presented.
Time frame: Week 26
Population: FA Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albiglutide + Insulin Glargine | Percentage of Participants Achieving HbA1c <7.0% Without Weight Gain at Week 26 | 49.8 Percentage of participants |
| Insulin Lispro + Insulin Glargine | Percentage of Participants Achieving HbA1c <7.0% Without Weight Gain at Week 26 | 21.4 Percentage of participants |
p-value: <0.000195% CI: [2.52, 4.86]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26
Hypoglycemic events with confirmed home plasma glucose monitoring \<3.9 millimoles per Liter and/or requiring third party intervention were severe, documented symptomatic (DS) and asymptomatic hypoglycemic events. Participants with more than one hypoglycemic event are counted in all categories reported. Any severe, documented symptomatic, and asymptomatic hypoglycemic events in 3-month intervals (i.e., from Day 0 to Week 12, \>Week 12 to Week 26) are presented.
Time frame: Up to Week 26
Population: Safety Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26 | Any event: Onset date falls under 0 to <= 12 weeks | 55.3 Percentage of participants |
| Albiglutide + Insulin Glargine | Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26 | Any event: Onset date falls > 12 to <= 26 Weeks | 60.3 Percentage of participants |
| Albiglutide + Insulin Glargine | Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26 | Severe: Onset date falls under 0 to <= 12 weeks | 1.8 Percentage of participants |
| Albiglutide + Insulin Glargine | Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26 | Severe: Onset date falls > 12 to <= 26 Weeks | 0.8 Percentage of participants |
| Albiglutide + Insulin Glargine | Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26 | DS: Onset date falls under 0 to <= 12 weeks | 33.8 Percentage of participants |
| Albiglutide + Insulin Glargine | Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26 | DS: Onset date falls > 12 to <= 26 Weeks | 40.8 Percentage of participants |
| Albiglutide + Insulin Glargine | Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26 | Asymptomatic: Onset date under 0 to <= 12 weeks | 38.3 Percentage of participants |
| Albiglutide + Insulin Glargine | Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26 | Asymptomatic: Onset date falls > 12 to <= 26 Weeks | 44.3 Percentage of participants |
| Insulin Lispro + Insulin Glargine | Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26 | Asymptomatic: Onset date falls > 12 to <= 26 Weeks | 54.7 Percentage of participants |
| Insulin Lispro + Insulin Glargine | Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26 | Any event: Onset date falls under 0 to <= 12 weeks | 79.2 Percentage of participants |
| Insulin Lispro + Insulin Glargine | Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26 | DS: Onset date falls under 0 to <= 12 weeks | 63.0 Percentage of participants |
| Insulin Lispro + Insulin Glargine | Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26 | Any event: Onset date falls > 12 to <= 26 Weeks | 79.4 Percentage of participants |
| Insulin Lispro + Insulin Glargine | Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26 | Asymptomatic: Onset date under 0 to <= 12 weeks | 56.9 Percentage of participants |
| Insulin Lispro + Insulin Glargine | Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26 | Severe: Onset date falls under 0 to <= 12 weeks | 3.6 Percentage of participants |
| Insulin Lispro + Insulin Glargine | Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26 | DS: Onset date falls > 12 to <= 26 Weeks | 62.0 Percentage of participants |
| Insulin Lispro + Insulin Glargine | Percentage of Participants With Events of Hypoglycemia With Confirmed Home Blood Glucose Monitoring and/or Third-party Intervention Through Week 26 | Severe: Onset date falls > 12 to <= 26 Weeks | 1.9 Percentage of participants |
Secondary
Percentage of Participants With Severe or Documented Symptomatic Hypoglycemia Through Week 26
Severe hypoglycemia was considered as an event requiring assistance of another person to actively administer carbohydrates, glucagon, or take other corrective actions. Plasma glucose concentrations may not be available during an event, but neurological recovery following the return of plasma glucose to normal was considered sufficient evidence that the event was induced by a low plasma glucose concentration. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia are accompanied by a measured plasma glucose concentration \<=70 milligrams per deciliters (mg/dL) (\<=3.9 millimoles per liters \[mmol/L\]).
Time frame: Up to Week 26
Population: FA Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Albiglutide + Insulin Glargine | Percentage of Participants With Severe or Documented Symptomatic Hypoglycemia Through Week 26 | 57.2 Percentage of participants |
| Insulin Lispro + Insulin Glargine | Percentage of Participants With Severe or Documented Symptomatic Hypoglycemia Through Week 26 | 75.0 Percentage of participants |
p-value: <0.000195% CI: [0.31, 0.6]Cochran-Mantel-Haenszel
Secondary
Total Daily Basal Insulin (Insulin Glargine) at Week 4, 10, 18, and 26 Visits
Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily basal insulin (insulin glargine) at Week 4, 10, 18, and 26 visits is presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.
Time frame: Weeks 4, 10, 18, and 26
Population: FA Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide + Insulin Glargine | Total Daily Basal Insulin (Insulin Glargine) at Week 4, 10, 18, and 26 Visits | Week 4, n=388,403 | 49.97 International Units | Standard Error 0.534 |
| Albiglutide + Insulin Glargine | Total Daily Basal Insulin (Insulin Glargine) at Week 4, 10, 18, and 26 Visits | Week 10, n=375,386 | 56.14 International Units | Standard Error 0.767 |
| Albiglutide + Insulin Glargine | Total Daily Basal Insulin (Insulin Glargine) at Week 4, 10, 18, and 26 Visits | Week 18, n=359,361 | 59.42 International Units | Standard Error 0.928 |
| Albiglutide + Insulin Glargine | Total Daily Basal Insulin (Insulin Glargine) at Week 4, 10, 18, and 26 Visits | Week 26, n=342,341 | 59.83 International Units | Standard Error 0.996 |
| Insulin Lispro + Insulin Glargine | Total Daily Basal Insulin (Insulin Glargine) at Week 4, 10, 18, and 26 Visits | Week 26, n=342,341 | 59.43 International Units | Standard Error 0.988 |
| Insulin Lispro + Insulin Glargine | Total Daily Basal Insulin (Insulin Glargine) at Week 4, 10, 18, and 26 Visits | Week 4, n=388,403 | 50.94 International Units | Standard Error 0.536 |
| Insulin Lispro + Insulin Glargine | Total Daily Basal Insulin (Insulin Glargine) at Week 4, 10, 18, and 26 Visits | Week 18, n=359,361 | 59.18 International Units | Standard Error 0.92 |
| Insulin Lispro + Insulin Glargine | Total Daily Basal Insulin (Insulin Glargine) at Week 4, 10, 18, and 26 Visits | Week 10, n=375,386 | 55.79 International Units | Standard Error 0.761 |
Comparison: Week 495% CI: [-2.25, 0.3]
Comparison: Week 1095% CI: [-1.64, 2.33]
Comparison: Week 1895% CI: [-2.21, 2.69]
Comparison: Week 26p-value: 0.769995% CI: [-2.25, 3.04]t-test, 2 sided
Secondary
Total Daily Bolus Insulin (Insulin Lispro) at Week 4, 10, 18, and 26 Visits
Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily bolus insulin (insulin lispro) at Week 4, 10, 18, and 26 visits is presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.
Time frame: Weeks 4, 10, 18, and 26
Population: FA Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide + Insulin Glargine | Total Daily Bolus Insulin (Insulin Lispro) at Week 4, 10, 18, and 26 Visits | Week 4, n=388,403 | 0.62 International Units | Standard Error 0.887 |
| Albiglutide + Insulin Glargine | Total Daily Bolus Insulin (Insulin Lispro) at Week 4, 10, 18, and 26 Visits | Week 10, n=375,386 | 1.90 International Units | Standard Error 1.147 |
| Albiglutide + Insulin Glargine | Total Daily Bolus Insulin (Insulin Lispro) at Week 4, 10, 18, and 26 Visits | Week 18, n=359,361 | 8.89 International Units | Standard Error 1.436 |
| Albiglutide + Insulin Glargine | Total Daily Bolus Insulin (Insulin Lispro) at Week 4, 10, 18, and 26 Visits | Week 26, n=342,341 | 10.64 International Units | Standard Error 1.523 |
| Insulin Lispro + Insulin Glargine | Total Daily Bolus Insulin (Insulin Lispro) at Week 4, 10, 18, and 26 Visits | Week 26, n=342,341 | 72.47 International Units | Standard Error 1.517 |
| Insulin Lispro + Insulin Glargine | Total Daily Bolus Insulin (Insulin Lispro) at Week 4, 10, 18, and 26 Visits | Week 4, n=388,403 | 56.67 International Units | Standard Error 0.892 |
| Insulin Lispro + Insulin Glargine | Total Daily Bolus Insulin (Insulin Lispro) at Week 4, 10, 18, and 26 Visits | Week 18, n=359,361 | 71.81 International Units | Standard Error 1.43 |
| Insulin Lispro + Insulin Glargine | Total Daily Bolus Insulin (Insulin Lispro) at Week 4, 10, 18, and 26 Visits | Week 10, n=375,386 | 66.66 International Units | Standard Error 1.144 |
Comparison: Week 495% CI: [-58.17, -53.94]
Comparison: Week 1095% CI: [-67.68, -61.85]
Comparison: Week 1895% CI: [-66.69, -59.15]
Comparison: week 26p-value: <0.000195% CI: [-65.85, -57.81]t-test, 2 sided
Secondary
Total Daily Insulin Dose at Week 26
Insulin dose at Week 26 was defined as the prescribed insulin dose at Week 25. Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily insulin dose at Week 26 is presented. Only those participants available at the specified time points were analyzed.
Time frame: Week 26
Population: FA Population. Only those participants available at the specified time points were analyzed.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Albiglutide + Insulin Glargine | Total Daily Insulin Dose at Week 26 | 70.36 International Units | Standard Error 2.16 |
| Insulin Lispro + Insulin Glargine | Total Daily Insulin Dose at Week 26 | 131.19 International Units | Standard Error 2.149 |
p-value: <0.000195% CI: [-66.57, -55.1]t-test, 2 sided
Secondary
Total Daily Insulin Dose at Week 4, Week 10 and Week 18
Based on MMRM model, prescribed total daily basal insulin dose was equal to Baseline prescribed total daily basal insulin dose + treatment + Baseline HbA1c category + region + age category + current use of metformin + visit week + treatment-by-visit week interaction + Baseline prescribed total daily basal insulin dose-by-visit week interaction. Total daily insulin dose at Week 4, Week 10 and Week 18 is presented. Only those participants available at the specified time points were analyzed represented by n=X,X in the category titles.
Time frame: Weeks 4, 10, and 18
Population: FA Population.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide + Insulin Glargine | Total Daily Insulin Dose at Week 4, Week 10 and Week 18 | Week 4, n=388,403 | 50.53 International Units | Standard Error 1.183 |
| Albiglutide + Insulin Glargine | Total Daily Insulin Dose at Week 4, Week 10 and Week 18 | Week 10, n=375,386 | 57.99 International Units | Standard Error 1.597 |
| Albiglutide + Insulin Glargine | Total Daily Insulin Dose at Week 4, Week 10 and Week 18 | Week 18, n=359,361 | 68.23 International Units | Standard Error 2.01 |
| Insulin Lispro + Insulin Glargine | Total Daily Insulin Dose at Week 4, Week 10 and Week 18 | Week 4, n=388,403 | 106.91 International Units | Standard Error 1.187 |
| Insulin Lispro + Insulin Glargine | Total Daily Insulin Dose at Week 4, Week 10 and Week 18 | Week 10, n=375,386 | 121.69 International Units | Standard Error 1.589 |
| Insulin Lispro + Insulin Glargine | Total Daily Insulin Dose at Week 4, Week 10 and Week 18 | Week 18, n=359,361 | 130.22 International Units | Standard Error 1.998 |
Comparison: Week 495% CI: [-59.19, -53.57]
Comparison: Week 1095% CI: [-67.78, -59.62]
Comparison: Week 1895% CI: [-67.29, -56.7]
Secondary
Total Number of Weekly Insulin Injections to Achieve Glycemic Control at Baseline/Randomization and Week 4, 10, 18, and 26
Total number of weekly insulin injections (7 days) to achieve glycemic control at Baseline/Randomization and Week 4, 10, 18, and 26 are presented. Only those participants available at the specified time points were analyzed represented by n=X,X in category titles.
Time frame: Baseline (Day -1) and Weeks 4, 10, 18 and 26
Population: FA Population.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Albiglutide + Insulin Glargine | Total Number of Weekly Insulin Injections to Achieve Glycemic Control at Baseline/Randomization and Week 4, 10, 18, and 26 | Week 4, n=388,403 | 8.11 Insulin Injections | Standard Deviation 1.506 |
| Albiglutide + Insulin Glargine | Total Number of Weekly Insulin Injections to Achieve Glycemic Control at Baseline/Randomization and Week 4, 10, 18, and 26 | Week 18, n=359,361 | 12.62 Insulin Injections | Standard Deviation 7.33 |
| Albiglutide + Insulin Glargine | Total Number of Weekly Insulin Injections to Achieve Glycemic Control at Baseline/Randomization and Week 4, 10, 18, and 26 | Week 10, n=375,386 | 9.06 Insulin Injections | Standard Deviation 3.121 |
| Albiglutide + Insulin Glargine | Total Number of Weekly Insulin Injections to Achieve Glycemic Control at Baseline/Randomization and Week 4, 10, 18, and 26 | Week 26, n=342,341 | 13.22 Insulin Injections | Standard Deviation 7.758 |
| Albiglutide + Insulin Glargine | Total Number of Weekly Insulin Injections to Achieve Glycemic Control at Baseline/Randomization and Week 4, 10, 18, and 26 | Baseline, n=401,412 | 28.79 Insulin Injections | Standard Deviation 1.47 |
| Insulin Lispro + Insulin Glargine | Total Number of Weekly Insulin Injections to Achieve Glycemic Control at Baseline/Randomization and Week 4, 10, 18, and 26 | Week 26, n=342,341 | 28.00 Insulin Injections | Standard Deviation 0 |
| Insulin Lispro + Insulin Glargine | Total Number of Weekly Insulin Injections to Achieve Glycemic Control at Baseline/Randomization and Week 4, 10, 18, and 26 | Baseline, n=401,412 | 28.00 Insulin Injections | Standard Deviation 0 |
| Insulin Lispro + Insulin Glargine | Total Number of Weekly Insulin Injections to Achieve Glycemic Control at Baseline/Randomization and Week 4, 10, 18, and 26 | Week 4, n=388,403 | 28.00 Insulin Injections | Standard Deviation 0 |
| Insulin Lispro + Insulin Glargine | Total Number of Weekly Insulin Injections to Achieve Glycemic Control at Baseline/Randomization and Week 4, 10, 18, and 26 | Week 10, n=375,386 | 28.00 Insulin Injections | Standard Deviation 0 |
| Insulin Lispro + Insulin Glargine | Total Number of Weekly Insulin Injections to Achieve Glycemic Control at Baseline/Randomization and Week 4, 10, 18, and 26 | Week 18, n=359,361 | 28.00 Insulin Injections | Standard Deviation 0 |