Diabetes Mellitus, Type 2
Conditions
Keywords
Type 2 Diabetes mellitus, Non-insulin dependent diabetes mellitus, Drug Therapy, Hypoglycemia,, Hyperglycemia
Brief summary
The purpose of this study is to evaluate the safety and effectiveness of alogliptin combined with metformin, once daily (QD) or twice daily (BID), in participants with Type 2 Diabetes.
Detailed description
There are approximately 19 million people in the United States who have been diagnosed with diabetes mellitus, of which 90% to 95% are type 2. The prevalence of type 2 diabetes varies among racial and ethnic populations and has been shown to correlate with age, obesity, family history, history of gestational diabetes and physical inactivity. Over the next decade, a marked increase in the number of adults with diabetes mellitus is expected. Metformin is the usual choice of first-line therapy for type 2 diabetes. Metformin targets insulin resistance in type 2 diabetes by inhibiting hepatic glucose production and stimulating glucose uptake in skeletal muscle and adipose tissue, which results in a long-term glucose-lowering effect. Alogliptin is an inhibitor of the dipeptidyl peptidase IV enzyme. Dipeptidyl peptidase-4 enzyme is thought to be primarily responsible for the in vivo degradation of 2 peptide hormones released in response to nutrient ingestion, namely glucagon-like peptide-1 and glucose-dependent insulinotropic peptide. Both peptides exert important effects on islet beta cells to stimulate glucose-dependent insulin secretion as well as regulating beta cell proliferation and cytoprotection. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, inhibits gastric emptying, glucagon secretion, and food intake. Glucose-dependent insulinotropic peptide has been shown to enhance insulin secretion by direct interaction with a glucose-dependent insulinotropic peptide -specific receptor on islet beta cells. The glucose-lowering actions of glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, are preserved in patients with type 2 diabetes mellitus. It is expected that inhibition of dipeptidyl peptidase IV will improve glycemic (glucose) control in patients with type 2 diabetes. Based on the potential, complimentary mechanisms of action of alogliptin and metformin, this study will compare the safety and efficacy of alogliptin and metformin (SYR-322MET) on improving glycemic control in patients with type 2 diabetes mellitus who are inadequately controlled by diet adjustment and exercise alone. Participants taking part in this study will receive dietary and exercise coaching, and will monitor their own blood glucose concentrations with a home glucose monitor. Participants will also be required to maintain a hypoglycemic diary throughout the course of the study. Participation in this study is expected to last up to 34 weeks.
Interventions
DRUGAlogliptin
Alogliptin tablets.
DRUGMetformin
Metformin capsules
Alogliptin placebo-matching tablets.
Metformin placebo-matching capsules.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Has historical diagnosis of Type 2 Diabetes Mellitus. * Has been treated with diet and exercise for at least 2 months prior to Screening, and has a Glycosylated Hemoglobin concentration between 7.5% and 10.0%, inclusive at Screening. * Has received less than 7 days of any antidiabetic medication within 2 months prior to Screening. * Body mass index greater than or equal to 23 kg/m\^2 and less than or equal to 45 kg/m\^2 (except for Asian or Asian-descendant subjects for whom the range is between 20 and 35 kg/ m\^2, inclusive). * Fasting C-peptide concentration greater than or equal to 0.8 ng/mL. * Regularly using other, non-excluded, medications must be on a stable dose for at least the 4 weeks prior to Screening. * Females of childbearing potential and males who are sexually active agree to routinely use adequate contraception from Screening throughout the duration of the study. * Able and willing to monitor their own blood glucose concentrations with a home glucose monitor and complete patient diaries.
Exclusion criteria
* Hemoglobin less than 12 g/dL for males and less than 10 g/dL for females at Screening Visit. * Has a history of any hemoglobinopathy that may affect determination of Glycosylated Hemoglobin. * Has a history of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening. * Has a history of treatment for diabetic gastric paresis, gastric banding, or gastric bypass surgery. * Has a history of diabetic ketoacidosis or hyperosmolar non-ketotic coma. * Has systolic blood pressure greater than or equal to 150 mmHg and /or diastolic pressure greater than or equal to 90 mmHg at Screening visit. * Has New York Heart Association Class III to IV heart failure. * Has a history of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 90 days prior to Screening. * Has Alanine aminotransferase greater than 3 times the upper limit of normal at Screening. * Has a history of alcohol or substance abuse with the 2 years prior to Screening. * Serum creatinine greater than or equal to 1.5 mg/dL for males and greater than or equal to 1.4 mg/dL for females. * Has history of cancer, other than squamous cell or basal cell carcinoma of the skin that has not been in full remission for at least 5 years prior to Screening. * Has a history of infection with human immunodeficiency virus, hepatitis B virus or hepatitis C virus. * Has any major illness or debility that in the investigator's opinion prohibits the subject from completing the study. * Has received any investigational drug within the 90 days prior to Screening. * Has a history of hypersensitivity or allergy to alogliptin, other DPP-4 inhibitors, metformin or related compounds. * Has used oral or systematically injected glucocorticoids or weight loss drugs prior to 2 months to screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | Baseline and Week 26. | The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in HbA1c Over Time | Baseline and Weeks 4, 8, 12, 16, and 20. | The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) was assessed at Weeks 4, 8, 12, 16 and 20. Least squares means are from an analysis of covariance (ANCOVA) model with treatment and geographic region as fixed effects, and baseline HbA1c as a covariate. |
| Change From Baseline in Fasting Plasma Glucose Over Time | Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26. | The change from Baseline in fasting plasma glucose was assessed at Weeks 1, 2, 4, 8, 12, 16, 20 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as fixed effects, and baseline fasting plasma glucose as a covariate. |
Countries
Czechia, Hungary, Israel, Lithuania, Mexico, Poland, Puerto Rico, Romania, Russia, Slovakia, South Africa, Ukraine, United States
Participant flow
Recruitment details
Participants took part in the study at 198 investigative sites worldwide from 16 November 2009 to 30 June 2011.
Pre-assignment details
Participants with a diagnosis of type 2 diabetes and glycemia inadequately controlled on diet and exercise alone were randomly assigned with equal probability to 1 of 7 treatment groups, including placebo, alogliptin alone, metformin alone or a combination of alogliptin and metformin.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Alogliptin placebo-matching tablets, orally, twice daily and Metformin placebo-matching capsules, orally, twice daily for up to 26 weeks. | 109 |
| Alogliptin 25 QD Alogliptin 25 mg, tablets, orally, once daily (QD) and Metformin placebo-matching capsules, orally, twice daily for up to 26 weeks. | 112 |
| Alogliptin 12.5 BID Alogliptin 12.5 mg, tablets, orally, twice daily (BID) and Metformin placebo-matching capsules, orally, twice daily for up to 26 weeks. | 113 |
| Metformin 500 BID Alogliptin placebo-matching tablets, orally, twice daily and Metformin 500 mg capsules, orally, twice daily for up to 26 weeks. | 114 |
| Metformin 1000 BID Alogliptin placebo-matching tablets, orally, twice daily and Metformin 1000 mg capsules, orally, twice daily for up to 26 weeks. | 111 |
| Alogliptin 12.5 BID + Metformin 500 BID Alogliptin 12.5mg, tablets, orally, twice daily and Metformin 500 mg, capsules, orally, twice daily for up to 26 weeks. | 111 |
| Alogliptin 12.5 BID + Metformin 1000 BID Alogliptin 12.5 mg, tablets, orally, twice daily and Metformin 1000 mg, capsules, orally, twice daily for up to 26 weeks. | 114 |
| Total | 784 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 4 | 4 | 7 | 3 | 2 | 5 | 11 |
| Overall Study | Lack of Efficacy | 9 | 3 | 6 | 2 | 1 | 2 | 1 |
| Overall Study | Lost to Follow-up | 4 | 8 | 7 | 2 | 5 | 2 | 2 |
| Overall Study | Major protocol deviation | 2 | 0 | 3 | 0 | 0 | 0 | 0 |
| Overall Study | Other | 1 | 0 | 1 | 0 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 2 | 0 | 2 | 1 | 1 | 1 | 1 |
| Overall Study | Pregnancy | 0 | 0 | 0 | 2 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 13 | 8 | 16 | 10 | 6 | 8 | 5 |
Baseline characteristics
| Characteristic | Alogliptin 25 QD | Total | Placebo | Alogliptin 12.5 BID + Metformin 1000 BID | Alogliptin 12.5 BID + Metformin 500 BID | Metformin 1000 BID | Metformin 500 BID | Alogliptin 12.5 BID |
|---|---|---|---|---|---|---|---|---|
| Age Continuous | 52.6 years STANDARD_DEVIATION 9.38 | 53.5 years STANDARD_DEVIATION 10.33 | 53.1 years STANDARD_DEVIATION 9.6 | 54.6 years STANDARD_DEVIATION 10.42 | 53.7 years STANDARD_DEVIATION 11.59 | 52.6 years STANDARD_DEVIATION 11.3 | 54.6 years STANDARD_DEVIATION 10.2 | 53.7 years STANDARD_DEVIATION 9.7 |
| Age, Customized <65 years | 103 participants | 675 participants | 100 participants | 96 participants | 91 participants | 94 participants | 95 participants | 96 participants |
| Age, Customized ≥65 years | 9 participants | 109 participants | 9 participants | 18 participants | 20 participants | 17 participants | 19 participants | 17 participants |
| Baseline HbA1c ≤8.5% | 67 participants | 465 participants | 65 participants | 67 participants | 66 participants | 66 participants | 67 participants | 67 participants |
| Baseline HbA1c >8.5% | 45 participants | 319 participants | 44 participants | 47 participants | 45 participants | 45 participants | 47 participants | 46 participants |
| Body Mass Index (BMI) | 30.81 kg/m^2 STANDARD_DEVIATION 5.219 | 30.71 kg/m^2 STANDARD_DEVIATION 5.173 | 31.15 kg/m^2 STANDARD_DEVIATION 5.269 | 31.04 kg/m^2 STANDARD_DEVIATION 5.375 | 30.92 kg/m^2 STANDARD_DEVIATION 5.353 | 30.51 kg/m^2 STANDARD_DEVIATION 5.043 | 30.19 kg/m^2 STANDARD_DEVIATION 4.842 | 30.36 kg/m^2 STANDARD_DEVIATION 5.159 |
| Diabetes Duration | 3.65 years STANDARD_DEVIATION 4.119 | 4.01 years STANDARD_DEVIATION 4.563 | 4.25 years STANDARD_DEVIATION 4.778 | 4.22 years STANDARD_DEVIATION 4.972 | 4.13 years STANDARD_DEVIATION 4.777 | 4.08 years STANDARD_DEVIATION 4.587 | 3.78 years STANDARD_DEVIATION 3.904 | 3.97 years STANDARD_DEVIATION 4.8 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 8 participants | 41 participants | 5 participants | 5 participants | 9 participants | 6 participants | 3 participants | 5 participants |
| Race/Ethnicity, Customized Asian | 17 participants | 143 participants | 20 participants | 26 participants | 20 participants | 20 participants | 19 participants | 21 participants |
| Race/Ethnicity, Customized Black or African American | 3 participants | 37 participants | 8 participants | 5 participants | 6 participants | 6 participants | 6 participants | 3 participants |
| Race/Ethnicity, Customized Hispanic or Latino | 43 participants | 302 participants | 45 participants | 39 participants | 45 participants | 42 participants | 45 participants | 43 participants |
| Race/Ethnicity, Customized Multiracial | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants | 0 participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 participants | 1 participants | 0 participants | 0 participants | 0 participants | 0 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 69 participants | 482 participants | 64 participants | 75 participants | 66 participants | 69 participants | 69 participants | 70 participants |
| Race/Ethnicity, Customized White | 84 participants | 561 participants | 76 participants | 78 participants | 76 participants | 79 participants | 85 participants | 83 participants |
| Sex: Female, Male Female | 64 Participants | 410 Participants | 54 Participants | 52 Participants | 63 Participants | 60 Participants | 67 Participants | 50 Participants |
| Sex: Female, Male Male | 48 Participants | 374 Participants | 55 Participants | 62 Participants | 48 Participants | 51 Participants | 47 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 50 / 106 | 38 / 112 | 34 / 110 | 44 / 109 | 43 / 111 | 40 / 106 | 37 / 114 |
| serious Total, serious adverse events | 3 / 106 | 1 / 112 | 4 / 110 | 3 / 109 | 2 / 111 | 2 / 106 | 2 / 114 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26
The change from Baseline to Week 26 in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound).
Time frame: Baseline and Week 26.
Population: Full analysis set (patients who took at least 1 dose of study medication) where baseline and at least 1 postbaseline assessment were available. Analysis includes only data collected on or after baseline and within 7 days after last dose of study medication or hyperglycemic rescue, whichever came first. Last observation carried forward was utilized.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | 0.15 percentage glycosylated hemoglobin | Standard Error 0.094 |
| Alogliptin 25 QD | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | -0.52 percentage glycosylated hemoglobin | Standard Error 0.094 |
| Alogliptin 12.5 BID | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | -0.56 percentage glycosylated hemoglobin | Standard Error 0.093 |
| Metformin 500 BID | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | -0.65 percentage glycosylated hemoglobin | Standard Error 0.094 |
| Metformin 1000 BID | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | -1.11 percentage glycosylated hemoglobin | Standard Error 0.092 |
| Alogliptin 12.5 BID + Metformin 500 BID | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | -1.22 percentage glycosylated hemoglobin | Standard Error 0.094 |
| Alogliptin 12.5 BID + Metformin 1000 BID | Change From Baseline in Glycosylated Hemoglobin (HbA1c) at Week 26 | -1.55 percentage glycosylated hemoglobin | Standard Error 0.09 |
Comparison: The primary efficacy analysis consisted of 2 separate sets of comparisons between each BID combination of alogliptin and metformin (alogliptin/metformin 12.5/500 mg BID and 12.5/1000 mg BID) and its constituent doses of alogliptin and metformin. The null hypothesis was that the combination of alogliptin and metformin had no additional effect on glycemic control at Week 26 either when compared with the constituent dose of alogliptin or with the constituent dose of metformin.p-value: <0.00195% CI: [-0.96, -0.37]ANCOVA
p-value: <0.00195% CI: [-0.87, -0.27]ANCOVA
p-value: <0.00195% CI: [-1.29, -0.71]ANCOVA
p-value: <0.00195% CI: [-0.73, -0.16]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose Over Time
The change from Baseline in fasting plasma glucose was assessed at Weeks 1, 2, 4, 8, 12, 16, 20 and 26. Least Squares Means were from an ANCOVA model with treatment and geographic region as fixed effects, and baseline fasting plasma glucose as a covariate.
Time frame: Baseline and Weeks 1, 2, 4, 8, 12, 16, 20 and 26.
Population: Full analysis set where a baseline assessment and at least 1 valid postbaseline assessment were available. Includes only data collected on or after baseline and within 1 day after the last dose of study medication or hyperglycemic rescue, whichever came first. Last observation carried forward was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Fasting Plasma Glucose Over Time | Week 26 (n=105, 112, 106, 106, 110, 106, 112) | 12.4 mg/dL | Standard Error 4.52 |
| Placebo | Change From Baseline in Fasting Plasma Glucose Over Time | Week 4 (n=105, 112, 106, 106, 110, 106, 111) | 7.2 mg/dL | Standard Error 3.69 |
| Placebo | Change From Baseline in Fasting Plasma Glucose Over Time | Week 8 (n=105, 112, 106, 106, 110, 106, 112) | 7.1 mg/dL | Standard Error 4 |
| Placebo | Change From Baseline in Fasting Plasma Glucose Over Time | Week 20 (n=105, 112, 106, 106, 110, 106, 112) | 8.7 mg/dL | Standard Error 4.36 |
| Placebo | Change From Baseline in Fasting Plasma Glucose Over Time | Week 12 (n=105, 112, 106, 106, 110, 106, 112) | 11.6 mg/dL | Standard Error 4.16 |
| Placebo | Change From Baseline in Fasting Plasma Glucose Over Time | Week 16 (n=105, 112, 106, 106, 110, 106, 112) | 10.1 mg/dL | Standard Error 4.17 |
| Placebo | Change From Baseline in Fasting Plasma Glucose Over Time | Week 2 (n=105, 112, 105, 102, 108, 106, 111) | 4.6 mg/dL | Standard Error 3.58 |
| Placebo | Change From Baseline in Fasting Plasma Glucose Over Time | Week 1 (n=102, 103, 94, 95, 104, 101, 109) | 5.7 mg/dL | Standard Error 3.4 |
| Alogliptin 25 QD | Change From Baseline in Fasting Plasma Glucose Over Time | Week 20 (n=105, 112, 106, 106, 110, 106, 112) | -9.2 mg/dL | Standard Error 4.22 |
| Alogliptin 25 QD | Change From Baseline in Fasting Plasma Glucose Over Time | Week 16 (n=105, 112, 106, 106, 110, 106, 112) | -7.1 mg/dL | Standard Error 4.04 |
| Alogliptin 25 QD | Change From Baseline in Fasting Plasma Glucose Over Time | Week 2 (n=105, 112, 105, 102, 108, 106, 111) | -7.4 mg/dL | Standard Error 3.46 |
| Alogliptin 25 QD | Change From Baseline in Fasting Plasma Glucose Over Time | Week 4 (n=105, 112, 106, 106, 110, 106, 111) | -11.5 mg/dL | Standard Error 3.57 |
| Alogliptin 25 QD | Change From Baseline in Fasting Plasma Glucose Over Time | Week 8 (n=105, 112, 106, 106, 110, 106, 112) | -10.9 mg/dL | Standard Error 3.87 |
| Alogliptin 25 QD | Change From Baseline in Fasting Plasma Glucose Over Time | Week 1 (n=102, 103, 94, 95, 104, 101, 109) | -3.9 mg/dL | Standard Error 3.38 |
| Alogliptin 25 QD | Change From Baseline in Fasting Plasma Glucose Over Time | Week 12 (n=105, 112, 106, 106, 110, 106, 112) | -9.7 mg/dL | Standard Error 4.03 |
| Alogliptin 25 QD | Change From Baseline in Fasting Plasma Glucose Over Time | Week 26 (n=105, 112, 106, 106, 110, 106, 112) | -6.1 mg/dL | Standard Error 4.37 |
| Alogliptin 12.5 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 26 (n=105, 112, 106, 106, 110, 106, 112) | -9.7 mg/dL | Standard Error 4.49 |
| Alogliptin 12.5 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 4 (n=105, 112, 106, 106, 110, 106, 111) | -16.6 mg/dL | Standard Error 3.67 |
| Alogliptin 12.5 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 1 (n=102, 103, 94, 95, 104, 101, 109) | -11.9 mg/dL | Standard Error 3.54 |
| Alogliptin 12.5 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 16 (n=105, 112, 106, 106, 110, 106, 112) | -14.7 mg/dL | Standard Error 4.15 |
| Alogliptin 12.5 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 8 (n=105, 112, 106, 106, 110, 106, 112) | -12.1 mg/dL | Standard Error 3.98 |
| Alogliptin 12.5 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 2 (n=105, 112, 105, 102, 108, 106, 111) | -11.6 mg/dL | Standard Error 3.58 |
| Alogliptin 12.5 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 20 (n=105, 112, 106, 106, 110, 106, 112) | -12.3 mg/dL | Standard Error 4.34 |
| Alogliptin 12.5 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 12 (n=105, 112, 106, 106, 110, 106, 112) | -14.7 mg/dL | Standard Error 4.14 |
| Metformin 500 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 16 (n=105, 112, 106, 106, 110, 106, 112) | -13.3 mg/dL | Standard Error 4.15 |
| Metformin 500 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 4 (n=105, 112, 106, 106, 110, 106, 111) | -16.9 mg/dL | Standard Error 3.67 |
| Metformin 500 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 12 (n=105, 112, 106, 106, 110, 106, 112) | -14.0 mg/dL | Standard Error 4.14 |
| Metformin 500 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 8 (n=105, 112, 106, 106, 110, 106, 112) | -11.8 mg/dL | Standard Error 3.98 |
| Metformin 500 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 26 (n=105, 112, 106, 106, 110, 106, 112) | -11.5 mg/dL | Standard Error 4.49 |
| Metformin 500 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 20 (n=105, 112, 106, 106, 110, 106, 112) | -10.9 mg/dL | Standard Error 4.34 |
| Metformin 500 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 1 (n=102, 103, 94, 95, 104, 101, 109) | -12.6 mg/dL | Standard Error 3.52 |
| Metformin 500 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 2 (n=105, 112, 105, 102, 108, 106, 111) | -14.5 mg/dL | Standard Error 3.63 |
| Metformin 1000 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 20 (n=105, 112, 106, 106, 110, 106, 112) | -35.1 mg/dL | Standard Error 4.25 |
| Metformin 1000 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 12 (n=105, 112, 106, 106, 110, 106, 112) | -30.7 mg/dL | Standard Error 4.06 |
| Metformin 1000 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 2 (n=105, 112, 105, 102, 108, 106, 111) | -22.2 mg/dL | Standard Error 3.53 |
| Metformin 1000 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 26 (n=105, 112, 106, 106, 110, 106, 112) | -31.9 mg/dL | Standard Error 4.41 |
| Metformin 1000 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 8 (n=105, 112, 106, 106, 110, 106, 112) | -30.7 mg/dL | Standard Error 3.91 |
| Metformin 1000 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 4 (n=105, 112, 106, 106, 110, 106, 111) | -29.0 mg/dL | Standard Error 3.6 |
| Metformin 1000 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 16 (n=105, 112, 106, 106, 110, 106, 112) | -33.5 mg/dL | Standard Error 4.07 |
| Metformin 1000 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 1 (n=102, 103, 94, 95, 104, 101, 109) | -23.1 mg/dL | Standard Error 3.36 |
| Alogliptin 12.5 BID + Metformin 500 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 2 (n=105, 112, 105, 102, 108, 106, 111) | -34.5 mg/dL | Standard Error 3.56 |
| Alogliptin 12.5 BID + Metformin 500 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 1 (n=102, 103, 94, 95, 104, 101, 109) | -32.7 mg/dL | Standard Error 3.41 |
| Alogliptin 12.5 BID + Metformin 500 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 8 (n=105, 112, 106, 106, 110, 106, 112) | -32.9 mg/dL | Standard Error 3.98 |
| Alogliptin 12.5 BID + Metformin 500 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 12 (n=105, 112, 106, 106, 110, 106, 112) | -31.6 mg/dL | Standard Error 4.14 |
| Alogliptin 12.5 BID + Metformin 500 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 16 (n=105, 112, 106, 106, 110, 106, 112) | -35.9 mg/dL | Standard Error 4.15 |
| Alogliptin 12.5 BID + Metformin 500 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 4 (n=105, 112, 106, 106, 110, 106, 111) | -37.6 mg/dL | Standard Error 3.67 |
| Alogliptin 12.5 BID + Metformin 500 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 20 (n=105, 112, 106, 106, 110, 106, 112) | -33.8 mg/dL | Standard Error 4.34 |
| Alogliptin 12.5 BID + Metformin 500 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 26 (n=105, 112, 106, 106, 110, 106, 112) | -31.7 mg/dL | Standard Error 4.49 |
| Alogliptin 12.5 BID + Metformin 1000 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 20 (n=105, 112, 106, 106, 110, 106, 112) | -44.6 mg/dL | Standard Error 4.22 |
| Alogliptin 12.5 BID + Metformin 1000 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 8 (n=105, 112, 106, 106, 110, 106, 112) | -43.8 mg/dL | Standard Error 3.87 |
| Alogliptin 12.5 BID + Metformin 1000 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 4 (n=105, 112, 106, 106, 110, 106, 111) | -44.1 mg/dL | Standard Error 3.58 |
| Alogliptin 12.5 BID + Metformin 1000 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 2 (n=105, 112, 105, 102, 108, 106, 111) | -43.6 mg/dL | Standard Error 3.48 |
| Alogliptin 12.5 BID + Metformin 1000 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 16 (n=105, 112, 106, 106, 110, 106, 112) | -47.7 mg/dL | Standard Error 4.04 |
| Alogliptin 12.5 BID + Metformin 1000 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 1 (n=102, 103, 94, 95, 104, 101, 109) | -36.3 mg/dL | Standard Error 3.29 |
| Alogliptin 12.5 BID + Metformin 1000 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 12 (n=105, 112, 106, 106, 110, 106, 112) | -44.7 mg/dL | Standard Error 4.03 |
| Alogliptin 12.5 BID + Metformin 1000 BID | Change From Baseline in Fasting Plasma Glucose Over Time | Week 26 (n=105, 112, 106, 106, 110, 106, 112) | -45.9 mg/dL | Standard Error 4.37 |
Secondary
Change From Baseline in HbA1c Over Time
The change from Baseline in HbA1c (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) was assessed at Weeks 4, 8, 12, 16 and 20. Least squares means are from an analysis of covariance (ANCOVA) model with treatment and geographic region as fixed effects, and baseline HbA1c as a covariate.
Time frame: Baseline and Weeks 4, 8, 12, 16, and 20.
Population: The full analysis set where a baseline assessment and at least 1 valid postbaseline assessment were available. The analysis includes only data collected on or after baseline and within 7 days after the last dose of study medication or hyperglycemic rescue, whichever came first. Last observation carried forward was utilized.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in HbA1c Over Time | Week 8 (n=102, 104, 104, 103, 108, 102, 111) | 0.08 percentage glycosylated hemoglobin | Standard Error 0.073 |
| Placebo | Change From Baseline in HbA1c Over Time | Week 12 (n=102, 104, 104, 103, 108, 102, 111) | 0.12 percentage glycosylated hemoglobin | Standard Error 0.081 |
| Placebo | Change From Baseline in HbA1c Over Time | Week 16 (n=102, 104, 104, 103, 108, 102, 111) | 0.13 percentage glycosylated hemoglobin | Standard Error 0.087 |
| Placebo | Change From Baseline in HbA1c Over Time | Week 20 (n=102, 104, 104, 103, 108, 102, 111) | 0.12 percentage glycosylated hemoglobin | Standard Error 0.092 |
| Placebo | Change From Baseline in HbA1c Over Time | Week 4 (n=95, 97, 89, 94, 102, 94, 101) | 0.09 percentage glycosylated hemoglobin | Standard Error 0.058 |
| Alogliptin 25 QD | Change From Baseline in HbA1c Over Time | Week 4 (n=95, 97, 89, 94, 102, 94, 101) | -0.34 percentage glycosylated hemoglobin | Standard Error 0.057 |
| Alogliptin 25 QD | Change From Baseline in HbA1c Over Time | Week 12 (n=102, 104, 104, 103, 108, 102, 111) | -0.53 percentage glycosylated hemoglobin | Standard Error 0.08 |
| Alogliptin 25 QD | Change From Baseline in HbA1c Over Time | Week 20 (n=102, 104, 104, 103, 108, 102, 111) | -0.57 percentage glycosylated hemoglobin | Standard Error 0.091 |
| Alogliptin 25 QD | Change From Baseline in HbA1c Over Time | Week 8 (n=102, 104, 104, 103, 108, 102, 111) | -0.51 percentage glycosylated hemoglobin | Standard Error 0.073 |
| Alogliptin 25 QD | Change From Baseline in HbA1c Over Time | Week 16 (n=102, 104, 104, 103, 108, 102, 111) | -0.58 percentage glycosylated hemoglobin | Standard Error 0.087 |
| Alogliptin 12.5 BID | Change From Baseline in HbA1c Over Time | Week 12 (n=102, 104, 104, 103, 108, 102, 111) | -0.62 percentage glycosylated hemoglobin | Standard Error 0.08 |
| Alogliptin 12.5 BID | Change From Baseline in HbA1c Over Time | Week 16 (n=102, 104, 104, 103, 108, 102, 111) | -0.63 percentage glycosylated hemoglobin | Standard Error 0.086 |
| Alogliptin 12.5 BID | Change From Baseline in HbA1c Over Time | Week 8 (n=102, 104, 104, 103, 108, 102, 111) | -0.58 percentage glycosylated hemoglobin | Standard Error 0.072 |
| Alogliptin 12.5 BID | Change From Baseline in HbA1c Over Time | Week 20 (n=102, 104, 104, 103, 108, 102, 111) | -0.59 percentage glycosylated hemoglobin | Standard Error 0.091 |
| Alogliptin 12.5 BID | Change From Baseline in HbA1c Over Time | Week 4 (n=95, 97, 89, 94, 102, 94, 101) | -0.42 percentage glycosylated hemoglobin | Standard Error 0.06 |
| Metformin 500 BID | Change From Baseline in HbA1c Over Time | Week 20 (n=102, 104, 104, 103, 108, 102, 111) | -0.68 percentage glycosylated hemoglobin | Standard Error 0.092 |
| Metformin 500 BID | Change From Baseline in HbA1c Over Time | Week 8 (n=102, 104, 104, 103, 108, 102, 111) | -0.59 percentage glycosylated hemoglobin | Standard Error 0.073 |
| Metformin 500 BID | Change From Baseline in HbA1c Over Time | Week 12 (n=102, 104, 104, 103, 108, 102, 111) | -0.68 percentage glycosylated hemoglobin | Standard Error 0.081 |
| Metformin 500 BID | Change From Baseline in HbA1c Over Time | Week 4 (n=95, 97, 89, 94, 102, 94, 101) | -0.37 percentage glycosylated hemoglobin | Standard Error 0.058 |
| Metformin 500 BID | Change From Baseline in HbA1c Over Time | Week 16 (n=102, 104, 104, 103, 108, 102, 111) | -0.72 percentage glycosylated hemoglobin | Standard Error 0.087 |
| Metformin 1000 BID | Change From Baseline in HbA1c Over Time | Week 4 (n=95, 97, 89, 94, 102, 94, 101) | -0.58 percentage glycosylated hemoglobin | Standard Error 0.056 |
| Metformin 1000 BID | Change From Baseline in HbA1c Over Time | Week 8 (n=102, 104, 104, 103, 108, 102, 111) | -0.86 percentage glycosylated hemoglobin | Standard Error 0.071 |
| Metformin 1000 BID | Change From Baseline in HbA1c Over Time | Week 12 (n=102, 104, 104, 103, 108, 102, 111) | -1.02 percentage glycosylated hemoglobin | Standard Error 0.079 |
| Metformin 1000 BID | Change From Baseline in HbA1c Over Time | Week 20 (n=102, 104, 104, 103, 108, 102, 111) | -1.14 percentage glycosylated hemoglobin | Standard Error 0.089 |
| Metformin 1000 BID | Change From Baseline in HbA1c Over Time | Week 16 (n=102, 104, 104, 103, 108, 102, 111) | -1.09 percentage glycosylated hemoglobin | Standard Error 0.085 |
| Alogliptin 12.5 BID + Metformin 500 BID | Change From Baseline in HbA1c Over Time | Week 20 (n=102, 104, 104, 103, 108, 102, 111) | -1.25 percentage glycosylated hemoglobin | Standard Error 0.092 |
| Alogliptin 12.5 BID + Metformin 500 BID | Change From Baseline in HbA1c Over Time | Week 16 (n=102, 104, 104, 103, 108, 102, 111) | -1.26 percentage glycosylated hemoglobin | Standard Error 0.087 |
| Alogliptin 12.5 BID + Metformin 500 BID | Change From Baseline in HbA1c Over Time | Week 8 (n=102, 104, 104, 103, 108, 102, 111) | -1.08 percentage glycosylated hemoglobin | Standard Error 0.073 |
| Alogliptin 12.5 BID + Metformin 500 BID | Change From Baseline in HbA1c Over Time | Week 4 (n=95, 97, 89, 94, 102, 94, 101) | -0.70 percentage glycosylated hemoglobin | Standard Error 0.058 |
| Alogliptin 12.5 BID + Metformin 500 BID | Change From Baseline in HbA1c Over Time | Week 12 (n=102, 104, 104, 103, 108, 102, 111) | -1.22 percentage glycosylated hemoglobin | Standard Error 0.081 |
| Alogliptin 12.5 BID + Metformin 1000 BID | Change From Baseline in HbA1c Over Time | Week 20 (n=102, 104, 104, 103, 108, 102, 111) | -1.54 percentage glycosylated hemoglobin | Standard Error 0.088 |
| Alogliptin 12.5 BID + Metformin 1000 BID | Change From Baseline in HbA1c Over Time | Week 16 (n=102, 104, 104, 103, 108, 102, 111) | -1.50 percentage glycosylated hemoglobin | Standard Error 0.084 |
| Alogliptin 12.5 BID + Metformin 1000 BID | Change From Baseline in HbA1c Over Time | Week 12 (n=102, 104, 104, 103, 108, 102, 111) | -1.40 percentage glycosylated hemoglobin | Standard Error 0.078 |
| Alogliptin 12.5 BID + Metformin 1000 BID | Change From Baseline in HbA1c Over Time | Week 8 (n=102, 104, 104, 103, 108, 102, 111) | -1.17 percentage glycosylated hemoglobin | Standard Error 0.07 |
| Alogliptin 12.5 BID + Metformin 1000 BID | Change From Baseline in HbA1c Over Time | Week 4 (n=95, 97, 89, 94, 102, 94, 101) | -0.75 percentage glycosylated hemoglobin | Standard Error 0.056 |