Diabetes Mellitus
Conditions
Keywords
Glucose Metabolism Disorder, Dysmetabolic Syndrome, Type II Diabetes, Diabetes Mellitus, Lipoatrophic, Dyslipidemia, Drug Therapy
Brief summary
The purpose of this study is to evaluate the efficacy and safety of alogliptin, once daily (QD), compared to glipizide in elderly diabetic patients who have not received treatment or are on a single oral medication.
Detailed description
Type 2 diabetes is among the most common chronic condition in adults 65 years of age or older. A recent National Health and Nutrition Examination Survey reported that more than 20% of adults aged 65 years or older have diabetes. These individuals are often under-treated with respect to glucose-lowering medications, and their care is complicated by the extent of their clinical and functional status. Age-related changes in physiology, diabetes-associated illnesses and other illnesses (such as renal, cardiac, and hepatic insufficiency), as well as use of multiple medications make standard oral anti-hyperglycemic therapy and insulin use problematic. In addition, hypoglycemia is more common and severe in older rather than younger patients taking oral antidiabetic drugs which can precipitate serious events such as falls and hip fractures. While avoidance of hypoglycemia is paramount in elderly diabetic patients, many commonly used medications are associated with a substantial risk for hypoglycemia. New classes of drug which avoid such complications in the elderly population are of increasing interest as this population continues to expand. Takeda is developing SYR-322 (alogliptin) for the improvement of glycemic control in patients with type 2 diabetes mellitus. Alogliptin is an inhibitor of the dipeptidyl peptidase IV enzyme. Dipeptidyl peptidase IV is thought to be primarily responsible for the degradation of 2 peptide hormones released in response to nutrient ingestion. It is expected that inhibition of dipeptidyl peptidase IV will improve glycemic (glucose) control in patients with type 2 diabetes. This study will compare the effectiveness and safety of alogliptin with that of glipizide (a commonly used diabetes medication) in adults who are 65 to 90 years of age with Type 2 diabetes. Individuals who participate in this study will either have failed diet and exercise therapy alone during the 2 months before Screening, or will have been receiving a single oral antidiabetic medication without obtaining good blood glucose (sugar) control. Each participant will be required to commit to screening visits. Study participation is anticipated to be up to 59 weeks.
Interventions
DRUGAlogliptin
Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks.
DRUGGlipizide
Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks.
Sponsors
Takeda
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
65 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
* Has a diagnosis of type 2 diabetes mellitus with either: * Failed diet and exercise therapy alone as demonstrated by inadequate glycemic control while receiving no antidiabetic treatment within the two months prior to Screening, or * Failed treatment with oral monotherapy alone (may include treatment with two or more antidiabetic agents if for less than 7 days) as demonstrated by inadequate glycemic control within the two months prior to Screening. * Body mass index greater than or equal to 23 kg/m2 and less than or equal to 45 kg/m2. * If 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 who are sexually active must agree to use a medically accepted means of contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study. * Able and willing to monitor their own blood glucose concentrations with a home glucose monitor. * No major illness or debility that in the investigator's opinion prohibits the participant from completing the study.
Exclusion criteria
* Systolic blood pressure greater than or equal to 160 mm Hg and/or diastolic pressure greater than or equal to 100 mm Hg. * Hemoglobin less than or equal to 12 g/dL for males or less than or equal to 10 g/dL for females. * Alanine aminotransferase greater than or equal to 3 times the upper limit of normal. * Calculated creatinine clearance less than or equal to 50 mL/min. * Thyroid-stimulating hormone level outside of the normal range. * 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. * History of laser treatment for proliferative diabetic retinopathy within the 6 months prior to Screening. * History of treated diabetic gastroparesis, gastric banding, or gastric bypass surgery. * New York Heart Association Class III or IV heart failure regardless of therapy. * History of coronary angioplasty, coronary stent placement, coronary bypass surgery, or myocardial infarction within the 6 months prior to Screening. * History of any hemoglobinopathy that may affect determination of glycosylated hemoglobin. * History of infection with Human Immunodeficiency Virus. * History of a psychiatric disorder that will affect the participant's ability to participate in the study. * History of angioedema in association with use of angiotensin-converting enzyme inhibitors or angiotensin-II receptor inhibitors. * History of alcohol or substance abuse within the 2 years prior to Screening. * History of treatment with any weight-loss drugs or oral or systemically injected glucocorticoids within the 3 months prior to Screening. * Receipt of any investigational drug within the 30 days prior to Screening. * Prior treatment in an investigational study of alogliptin. * Clinically significant medical abnormality or disease or clinically significant abnormal findings at Screening (other than type 2 diabetes) that, in the opinion of the investigator, should exclude the participant from the study. * Has donated more than 400 mL of blood within the 90 days preceding their participation in the study. * Has hypersensitivity or has had an anaphylactic reaction(s) to any DPP-4 inhibitor drug.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin at Week 52. | Baseline and Week 52. | The change in the percentage of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 52 or final visit and glycosylated hemoglobin collected at baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Hemoglobin | Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 26, Week 34 and Week 42. | The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at each week indicated including final visit relative to baseline. |
| Incidence of Hypoglycemia | On occurrence (up to 52 weeks). | Percentage of participants with at least one hypoglycemic episode during 52 week study. |
| Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | On Occurrence (up to 52 weeks). | The number of participants with a fasting plasma glucose value ≥ to 200 mg per dL during the 52 week study. |
| Incidence of Hyperglycemic Rescue | On Occurrence (up to 52 weeks). | The number of participants requiring rescue for failing to achieve pre-specified glycemic targets during the 52 week study. |
| Change From Baseline in Fasting Plasma Glucose | Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 26, Week 34, Week 42 and Week 52. | The change in the value of fasting plasma glucose collected at each week indicated including final visit relative to baseline. |
| Change From Baseline in 2-hour Postprandial Glucose | Baseline and Week 52. | The change in postprandial (after eating a meal) glucose levels at week 52 relative to baseline. Standard 2-hour postprandial glucose (PPG) tests performed following an overnight fast and evaluated right before and after a 120-minute (2-hour) timeframe relative to ingestion of a standard oral glucose drink. |
| Change From Baseline in Fasting Proinsulin | Baseline, Week 12, Week 26, Week 42 and Week 52. | The change between the value of fasting proinsulin collected at each week indicated including final visit relative to baseline. |
| Change From Baseline in Proinsulin/Insulin Ratio | Baseline, Week 12, Week 26, Week 42 and Week 52. | The change between the ratio value of proinsulin and insulin collected at each week indicated including final visit relative to baseline. |
| Change From Baseline in Insulin | Baseline, Week 12, Week 26, Week 42 and Week 52. | The change between the value of insulin collected at each week indicated including final visit relative to baseline. |
| Change From Baseline in Body Weight | Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52. | The change in body weight measured at each week indicated including final visit from baseline. |
| Change From Baseline in Serum Lipids (Total Cholesterol) | Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52. | The change in total cholesterol measured at each week indicated including final visit from baseline. |
| Change From Baseline in Serum Lipids (High-Density Lipoprotein Cholesterol) | Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52. | The change in high-density lipoprotein cholesterol measured at each week indicated including final visit from baseline. |
| Change From Baseline in Serum Lipids (Low-Density Lipoprotein Cholesterol) | Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52. | The change in low-density lipoprotein cholesterol measured at each week indicated including final visit from baseline. |
| Change From Baseline in Serum Lipids (Triglycerides) | Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52. | The change in triglycerides measured at each week indicated including final visit from baseline. |
| Change From Baseline in High Sensitivity C-reactive Protein | Baseline, Week 12, Week 26, Week 42 and Week 52. | The change between the high sensitivity C-reactive protein value collected at each week indicated including final visit from baseline. |
| Incidence of Subjects Achieving Glycosylated Hemoglobin <=7% | Baseline and Week 52. | The percentage of participants with a value for the percentage of glycosylated hemoglobin (HbA1c; the percentage of hemoglobin that is bound to glucose) less than or equal to 6.5 and 7.0% during the 52 week study. |
| Incidence of Glycosylated Hemoglobin Decrease From Baseline. | Baseline and Week 52. | The percentage of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 0.5, 1.0, 1.5 and 2.0% during the 52 week study. |
| Homeostasis Model Assessment of Beta Cell Function | Baseline, Week 12, Week 26, Week 42 and Week 52. | The change between homeostasis model assessment of beta cell function collected at each week indicated including final visit relative to baseline. Homeostasis model assessment of beta cell function measures beta cell function, calculated by a constant (20) times insulin, divided by fasting plasma glucose minus a constant (3.5). |
Countries
Hungary, India, Israel, Mexico, Peru, Poland, Romania, Russia, South Africa, Ukraine, United States
Participant flow
Recruitment details
Participants enrolled at 110 investigative sites in Hungary, India, Israel, Mexico, Peru, Poland, Romania, Russia, South Africa, the Ukraine and the United States from 25 June 2008 to 30 August 2010.
Pre-assignment details
Participants with a historical diagnosis of type 2 diabetes mellitus were enrolled in one of two, once-daily (QD) treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| Alogliptin 25 mg QD Alogliptin 25 mg, tablets, orally, once daily and glipizide placebo matching tablets, orally, once daily for up to 52 weeks. | 222 |
| Glipizide 5 mg QD Alogliptin placebo-matching tablets, orally, once daily and glipizide 5 mg to 10 mg, tablets, orally, once daily up to 52 weeks. | 219 |
| Total | 441 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 16 | 20 |
| Overall Study | Hyperglycemic Rescue | 55 | 47 |
| Overall Study | Lost to Follow-up | 0 | 4 |
| Overall Study | Other | 2 | 0 |
| Overall Study | Protocol Violation | 4 | 7 |
| Overall Study | Withdrawal by Subject | 12 | 16 |
Baseline characteristics
| Characteristic | Alogliptin 25 mg QD | Glipizide 5 mg QD | Total |
|---|---|---|---|
| Age Continuous | 70.1 years STANDARD_DEVIATION 4.42 | 69.8 years STANDARD_DEVIATION 4.07 | 69.9 years STANDARD_DEVIATION 4.24 |
| Age, Customized <75 years | 186 participants | 193 participants | 379 participants |
| Age, Customized ≥75 years | 36 participants | 26 participants | 62 participants |
| Body Mass Index (BMI) | 29.58 kg/m2 STANDARD_DEVIATION 4.348 | 30.02 kg/m2 STANDARD_DEVIATION 4.459 | 29.79 kg/m2 STANDARD_DEVIATION 4.404 |
| Diabetes duration | 6.25 years STANDARD_DEVIATION 6.285 | 5.94 years STANDARD_DEVIATION 6.276 | 6.10 years STANDARD_DEVIATION 6.275 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 79 Participants | 70 Participants | 149 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 143 Participants | 149 Participants | 292 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Glomerular Filtration Rate (GFR) | 73.62 mL/min/1.73 m2 STANDARD_DEVIATION 14.762 | 72.89 mL/min/1.73 m2 STANDARD_DEVIATION 15.524 | 73.26 mL/min/1.73 m2 STANDARD_DEVIATION 15.133 |
| Race (NIH/OMB) American Indian or Alaska Native | 12 Participants | 13 Participants | 25 Participants |
| Race (NIH/OMB) Asian | 19 Participants | 26 Participants | 45 Participants |
| Race (NIH/OMB) Black or African American | 16 Participants | 20 Participants | 36 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 6 Participants | 12 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 169 Participants | 154 Participants | 323 Participants |
| Sex: Female, Male Female | 120 Participants | 123 Participants | 243 Participants |
| Sex: Female, Male Male | 102 Participants | 96 Participants | 198 Participants |
| Smoking history Current smoker | 16 participants | 11 participants | 27 participants |
| Smoking history Ex-smoker | 46 participants | 40 participants | 86 participants |
| Smoking history Never smoked | 160 participants | 168 participants | 328 participants |
| Weight | 78.60 kg STANDARD_DEVIATION 14.842 | 78.81 kg STANDARD_DEVIATION 15.239 | 78.70 kg STANDARD_DEVIATION 15.024 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 103 / 222 | 105 / 219 |
| serious Total, serious adverse events | 16 / 222 | 13 / 219 |
Outcome results
Primary
Change From Baseline in Glycosylated Hemoglobin at Week 52.
The change in the percentage of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at week 52 or final visit and glycosylated hemoglobin collected at baseline.
Time frame: Baseline and Week 52.
Population: Randomized participants who received at least 1 dose of study drug, had measurements at Baseline and at the visit, and who met pre-specified criteria (no major protocol violations) for inclusion in the Per Protocol Set. Missing data were imputed using last observation carried forward (LOCF).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin at Week 52. | -0.14 percentage of Glycosylated Hemoglobin | Standard Error 0.063 |
| Glipizide 5 mg QD | Change From Baseline in Glycosylated Hemoglobin at Week 52. | -0.09 percentage of Glycosylated Hemoglobin | Standard Error 0.067 |
Comparison: Primary null hypothesis: the average Week 52 HbA1c change from Baseline for alogliptin is inferior to that for glipizide (1-sided 97.5% CI \[alpha=0.025\] compared to non-inferiority margin of 0.4%). If the primary null hypothesis was rejected (non-inferiority demonstrated), an additional comparison for statistical superiority of alogliptin was performed. The CI was re-evaluated; statistical superiority declared if the upper limit was \< 0%.ANCOVA
Secondary
Change From Baseline in 2-hour Postprandial Glucose
The change in postprandial (after eating a meal) glucose levels at week 52 relative to baseline. Standard 2-hour postprandial glucose (PPG) tests performed following an overnight fast and evaluated right before and after a 120-minute (2-hour) timeframe relative to ingestion of a standard oral glucose drink.
Time frame: Baseline and Week 52.
Population: All randomized participants who had at least 1 dose of study medication (full analysis set).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg QD | Change From Baseline in 2-hour Postprandial Glucose | Week 52 PPG level (n=109; n=93) | -5.80 mg/dL | Standard Error 5.53 |
| Alogliptin 25 mg QD | Change From Baseline in 2-hour Postprandial Glucose | Week 52 PPG excursion (n=109; n=93) | 1.82 mg/dL | Standard Error 4.434 |
| Glipizide 5 mg QD | Change From Baseline in 2-hour Postprandial Glucose | Week 52 PPG level (n=109; n=93) | 6.30 mg/dL | Standard Error 5.989 |
| Glipizide 5 mg QD | Change From Baseline in 2-hour Postprandial Glucose | Week 52 PPG excursion (n=109; n=93) | 7.17 mg/dL | Standard Error 4.804 |
Secondary
Change From Baseline in Body Weight
The change in body weight measured at each week indicated including final visit from baseline.
Time frame: Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.
Population: All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg QD | Change From Baseline in Body Weight | Week 26 (n=215; n=204) | -0.68 kg | Standard Error 0.188 |
| Alogliptin 25 mg QD | Change From Baseline in Body Weight | Week 12 (n=215; n=203) | -0.52 kg | Standard Error 0.142 |
| Alogliptin 25 mg QD | Change From Baseline in Body Weight | Week 42 (n=215; n=204) | -0.72 kg | Standard Error 0.211 |
| Alogliptin 25 mg QD | Change From Baseline in Body Weight | Week 52 (n=215; n=204) | -0.62 kg | Standard Error 0.227 |
| Alogliptin 25 mg QD | Change From Baseline in Body Weight | Week 8 (n=213; n=200) | -0.42 kg | Standard Error 0.118 |
| Glipizide 5 mg QD | Change From Baseline in Body Weight | Week 52 (n=215; n=204) | 0.60 kg | Standard Error 0.233 |
| Glipizide 5 mg QD | Change From Baseline in Body Weight | Week 8 (n=213; n=200) | 0.55 kg | Standard Error 0.122 |
| Glipizide 5 mg QD | Change From Baseline in Body Weight | Week 12 (n=215; n=203) | 0.42 kg | Standard Error 0.146 |
| Glipizide 5 mg QD | Change From Baseline in Body Weight | Week 26 (n=215; n=204) | 0.66 kg | Standard Error 0.193 |
| Glipizide 5 mg QD | Change From Baseline in Body Weight | Week 42 (n=215; n=204) | 0.57 kg | Standard Error 0.216 |
Secondary
Change From Baseline in Fasting Plasma Glucose
The change in the value of fasting plasma glucose collected at each week indicated including final visit relative to baseline.
Time frame: Baseline, Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 26, Week 34, Week 42 and Week 52.
Population: All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 2 (n=196; n=199) | -3.8 mg/dL | Standard Error 1.93 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 4 (n=217; n=213) | -7.7 mg/dL | Standard Error 1.93 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 8 (n=217; n=214) | -8.9 mg/dL | Standard Error 1.76 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 12 (n=217; n=214) | -10.2 mg/dL | Standard Error 1.84 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 16 (n=217; n=214) | -7.9 mg/dL | Standard Error 1.85 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 20 (n=217; n=214) | -9.8 mg/dL | Standard Error 1.78 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 26 (n=217; n=214) | -7.9 mg/dL | Standard Error 1.97 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 34 (n=217; n=214) | -5.4 mg/dL | Standard Error 1.98 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 42 (n=217; n=214) | -3.6 mg/dL | Standard Error 2.13 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 52 (n=217; n=214) | -2.4 mg/dL | Standard Error 2.24 |
| Glipizide 5 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 34 (n=217; n=214) | -5.7 mg/dL | Standard Error 1.99 |
| Glipizide 5 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 2 (n=196; n=199) | -5.0 mg/dL | Standard Error 1.91 |
| Glipizide 5 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 20 (n=217; n=214) | -8.7 mg/dL | Standard Error 1.79 |
| Glipizide 5 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 4 (n=217; n=213) | -7.6 mg/dL | Standard Error 1.95 |
| Glipizide 5 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 52 (n=217; n=214) | -4.2 mg/dL | Standard Error 2.26 |
| Glipizide 5 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 8 (n=217; n=214) | -8.7 mg/dL | Standard Error 1.77 |
| Glipizide 5 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 26 (n=217; n=214) | -6.2 mg/dL | Standard Error 1.99 |
| Glipizide 5 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 12 (n=217; n=214) | -9.9 mg/dL | Standard Error 1.86 |
| Glipizide 5 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 42 (n=217; n=214) | -7.4 mg/dL | Standard Error 2.14 |
| Glipizide 5 mg QD | Change From Baseline in Fasting Plasma Glucose | Week 16 (n=217; n=214) | -11.4 mg/dL | Standard Error 1.86 |
Secondary
Change From Baseline in Fasting Proinsulin
The change between the value of fasting proinsulin collected at each week indicated including final visit relative to baseline.
Time frame: Baseline, Week 12, Week 26, Week 42 and Week 52.
Population: All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg QD | Change From Baseline in Fasting Proinsulin | Week 12 (n=207; n=186) | -6.0 pmol/L | Standard Error 0.99 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Proinsulin | Week 26 (n=211; n=194) | -4.6 pmol/L | Standard Error 1.49 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Proinsulin | Week 42 (n=211; n=194) | -4.6 pmol/L | Standard Error 1.48 |
| Alogliptin 25 mg QD | Change From Baseline in Fasting Proinsulin | Week 52 (n=211; n=194) | -4.9 pmol/L | Standard Error 1.42 |
| Glipizide 5 mg QD | Change From Baseline in Fasting Proinsulin | Week 52 (n=211; n=194) | 3.0 pmol/L | Standard Error 1.48 |
| Glipizide 5 mg QD | Change From Baseline in Fasting Proinsulin | Week 12 (n=207; n=186) | 1.0 pmol/L | Standard Error 1.05 |
| Glipizide 5 mg QD | Change From Baseline in Fasting Proinsulin | Week 42 (n=211; n=194) | 3.1 pmol/L | Standard Error 1.54 |
| Glipizide 5 mg QD | Change From Baseline in Fasting Proinsulin | Week 26 (n=211; n=194) | 3.0 pmol/L | Standard Error 1.56 |
Secondary
Change From Baseline in Glycosylated Hemoglobin
The change in the value of glycosylated hemoglobin (the concentration of glucose bound to hemoglobin as a percent of the absolute maximum that can be bound) collected at each week indicated including final visit relative to baseline.
Time frame: Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 26, Week 34 and Week 42.
Population: Randomized participants who received at least 1 dose of study drug, had measurements at Baseline and at the visit, and who met pre-specified criteria (no major protocol violations) for inclusion in the Per Protocol Set. Missing data were imputed using last observation carried forward (LOCF).
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin | Week 4 (n=175; n=148) | -0.14 percentage of Glycosylated Hemoglobin | Standard Error 0.047 |
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin | Week 8 (n=180; n=161) | -0.27 percentage of Glycosylated Hemoglobin | Standard Error 0.051 |
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin | Week 12 (n=180; n=162) | -0.34 percentage of Glycosylated Hemoglobin | Standard Error 0.053 |
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin | Week 16 (n=180; n=162) | -0.31 percentage of Glycosylated Hemoglobin | Standard Error 0.05 |
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin | Week 20 (n=180; n=162) | -0.31 percentage of Glycosylated Hemoglobin | Standard Error 0.051 |
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin | Week 26 (n=180; n=162) | -0.28 percentage of Glycosylated Hemoglobin | Standard Error 0.052 |
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin | Week 34 (n=180; n=162) | -0.21 percentage of Glycosylated Hemoglobin | Standard Error 0.056 |
| Alogliptin 25 mg QD | Change From Baseline in Glycosylated Hemoglobin | Week 42 (n=180; n=162) | -0.17 percentage of Glycosylated Hemoglobin | Standard Error 0.062 |
| Glipizide 5 mg QD | Change From Baseline in Glycosylated Hemoglobin | Week 42 (n=180; n=162) | -0.17 percentage of Glycosylated Hemoglobin | Standard Error 0.065 |
| Glipizide 5 mg QD | Change From Baseline in Glycosylated Hemoglobin | Week 4 (n=175; n=148) | -0.11 percentage of Glycosylated Hemoglobin | Standard Error 0.051 |
| Glipizide 5 mg QD | Change From Baseline in Glycosylated Hemoglobin | Week 20 (n=180; n=162) | -0.27 percentage of Glycosylated Hemoglobin | Standard Error 0.054 |
| Glipizide 5 mg QD | Change From Baseline in Glycosylated Hemoglobin | Week 8 (n=180; n=161) | -0.23 percentage of Glycosylated Hemoglobin | Standard Error 0.054 |
| Glipizide 5 mg QD | Change From Baseline in Glycosylated Hemoglobin | Week 34 (n=180; n=162) | -0.21 percentage of Glycosylated Hemoglobin | Standard Error 0.059 |
| Glipizide 5 mg QD | Change From Baseline in Glycosylated Hemoglobin | Week 12 (n=180; n=162) | -0.25 percentage of Glycosylated Hemoglobin | Standard Error 0.055 |
| Glipizide 5 mg QD | Change From Baseline in Glycosylated Hemoglobin | Week 26 (n=180; n=162) | -0.25 percentage of Glycosylated Hemoglobin | Standard Error 0.055 |
| Glipizide 5 mg QD | Change From Baseline in Glycosylated Hemoglobin | Week 16 (n=180; n=162) | -0.32 percentage of Glycosylated Hemoglobin | Standard Error 0.052 |
Secondary
Change From Baseline in High Sensitivity C-reactive Protein
The change between the high sensitivity C-reactive protein value collected at each week indicated including final visit from baseline.
Time frame: Baseline, Week 12, Week 26, Week 42 and Week 52.
Population: All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg QD | Change From Baseline in High Sensitivity C-reactive Protein | Week 12 (n=209; n=192) | 0.45 mg/L | Standard Error 0.699 |
| Alogliptin 25 mg QD | Change From Baseline in High Sensitivity C-reactive Protein | Week 26 (n=212; n=198) | -0.02 mg/L | Standard Error 0.682 |
| Alogliptin 25 mg QD | Change From Baseline in High Sensitivity C-reactive Protein | Week 52 (n=212; n=198) | 0.01 mg/L | Standard Error 0.656 |
| Alogliptin 25 mg QD | Change From Baseline in High Sensitivity C-reactive Protein | Week 42 (n=212; n=198) | 0.33 mg/L | Standard Error 0.736 |
| Glipizide 5 mg QD | Change From Baseline in High Sensitivity C-reactive Protein | Week 52 (n=212; n=198) | 0.21 mg/L | Standard Error 0.679 |
| Glipizide 5 mg QD | Change From Baseline in High Sensitivity C-reactive Protein | Week 12 (n=209; n=192) | 0.10 mg/L | Standard Error 0.73 |
| Glipizide 5 mg QD | Change From Baseline in High Sensitivity C-reactive Protein | Week 26 (n=212; n=198) | 0.47 mg/L | Standard Error 0.706 |
| Glipizide 5 mg QD | Change From Baseline in High Sensitivity C-reactive Protein | Week 42 (n=212; n=198) | 0.53 mg/L | Standard Error 0.762 |
Secondary
Change From Baseline in Insulin
The change between the value of insulin collected at each week indicated including final visit relative to baseline.
Time frame: Baseline, Week 12, Week 26, Week 42 and Week 52.
Population: All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg QD | Change From Baseline in Insulin | Week 12 (n=207; n=188) | -2.36 mcIU/mL | Standard Error 0.673 |
| Alogliptin 25 mg QD | Change From Baseline in Insulin | Week 26 (n=210; n=194) | -0.41 mcIU/mL | Standard Error 1.548 |
| Alogliptin 25 mg QD | Change From Baseline in Insulin | Week 42 (n=210; n=194) | -0.58 mcIU/mL | Standard Error 1.254 |
| Alogliptin 25 mg QD | Change From Baseline in Insulin | Week 52 (n=210; n=194) | -1.72 mcIU/mL | Standard Error 1.731 |
| Glipizide 5 mg QD | Change From Baseline in Insulin | Week 52 (n=210; n=194) | 3.15 mcIU/mL | Standard Error 1.801 |
| Glipizide 5 mg QD | Change From Baseline in Insulin | Week 12 (n=207; n=188) | 0.84 mcIU/mL | Standard Error 0.707 |
| Glipizide 5 mg QD | Change From Baseline in Insulin | Week 42 (n=210; n=194) | 1.53 mcIU/mL | Standard Error 1.305 |
| Glipizide 5 mg QD | Change From Baseline in Insulin | Week 26 (n=210; n=194) | 3.03 mcIU/mL | Standard Error 1.611 |
Secondary
Change From Baseline in Proinsulin/Insulin Ratio
The change between the ratio value of proinsulin and insulin collected at each week indicated including final visit relative to baseline.
Time frame: Baseline, Week 12, Week 26, Week 42 and Week 52.
Population: All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg QD | Change From Baseline in Proinsulin/Insulin Ratio | Week 12 (n=206; n=185) | -0.288 ratio | Standard Error 0.1035 |
| Alogliptin 25 mg QD | Change From Baseline in Proinsulin/Insulin Ratio | Week 26 (n=210; n=193) | -0.253 ratio | Standard Error 0.4333 |
| Alogliptin 25 mg QD | Change From Baseline in Proinsulin/Insulin Ratio | Week 42 (n=210; n=193) | -0.289 ratio | Standard Error 0.15 |
| Alogliptin 25 mg QD | Change From Baseline in Proinsulin/Insulin Ratio | Week 52 (n=210; n=193) | -0.155 ratio | Standard Error 0.0899 |
| Glipizide 5 mg QD | Change From Baseline in Proinsulin/Insulin Ratio | Week 52 (n=210; n=193) | -0.057 ratio | Standard Error 0.0938 |
| Glipizide 5 mg QD | Change From Baseline in Proinsulin/Insulin Ratio | Week 12 (n=206; n=185) | 0.053 ratio | Standard Error 0.1092 |
| Glipizide 5 mg QD | Change From Baseline in Proinsulin/Insulin Ratio | Week 42 (n=210; n=193) | 0.183 ratio | Standard Error 0.1565 |
| Glipizide 5 mg QD | Change From Baseline in Proinsulin/Insulin Ratio | Week 26 (n=210; n=193) | 0.562 ratio | Standard Error 0.452 |
Secondary
Change From Baseline in Serum Lipids (High-Density Lipoprotein Cholesterol)
The change in high-density lipoprotein cholesterol measured at each week indicated including final visit from baseline.
Time frame: Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.
Population: All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (High-Density Lipoprotein Cholesterol) | Week 12 (n=212; n=201) | 0.4 mg/dL | Standard Error 0.47 |
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (High-Density Lipoprotein Cholesterol) | Week 42 (n=212; n=201) | 1.4 mg/dL | Standard Error 0.59 |
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (High-Density Lipoprotein Cholesterol) | Week 26 (n=212; n=201) | 1.7 mg/dL | Standard Error 0.5 |
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (High-Density Lipoprotein Cholesterol) | Week 52 (n=212; n=201) | 0.8 mg/dL | Standard Error 0.5 |
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (High-Density Lipoprotein Cholesterol) | Week 8 (n=206; n=193) | -0.1 mg/dL | Standard Error 0.59 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (High-Density Lipoprotein Cholesterol) | Week 52 (n=212; n=201) | 0.3 mg/dL | Standard Error 0.51 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (High-Density Lipoprotein Cholesterol) | Week 8 (n=206; n=193) | 1.2 mg/dL | Standard Error 0.61 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (High-Density Lipoprotein Cholesterol) | Week 12 (n=212; n=201) | 0.5 mg/dL | Standard Error 0.48 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (High-Density Lipoprotein Cholesterol) | Week 26 (n=212; n=201) | 0.2 mg/dL | Standard Error 0.52 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (High-Density Lipoprotein Cholesterol) | Week 42 (n=212; n=201) | 0.1 mg/dL | Standard Error 0.61 |
Secondary
Change From Baseline in Serum Lipids (Low-Density Lipoprotein Cholesterol)
The change in low-density lipoprotein cholesterol measured at each week indicated including final visit from baseline.
Time frame: Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.
Population: All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (Low-Density Lipoprotein Cholesterol) | Week 12 (n=208; n=195) | -2.0 mg/dL | Standard Error 1.75 |
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (Low-Density Lipoprotein Cholesterol) | Week 42 (n=208; n=197) | 1.2 mg/dL | Standard Error 1.79 |
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (Low-Density Lipoprotein Cholesterol) | Week 26 (n=208; n=196) | 3.1 mg/dL | Standard Error 1.67 |
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (Low-Density Lipoprotein Cholesterol) | Week 52 (n=209; n=197) | 0.9 mg/dL | Standard Error 1.83 |
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (Low-Density Lipoprotein Cholesterol) | Week 8 (n=200; n=185) | -3.2 mg/dL | Standard Error 1.7 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (Low-Density Lipoprotein Cholesterol) | Week 52 (n=209; n=197) | -1.4 mg/dL | Standard Error 1.88 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (Low-Density Lipoprotein Cholesterol) | Week 8 (n=200; n=185) | -2.8 mg/dL | Standard Error 1.76 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (Low-Density Lipoprotein Cholesterol) | Week 12 (n=208; n=195) | -2.4 mg/dL | Standard Error 1.81 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (Low-Density Lipoprotein Cholesterol) | Week 26 (n=208; n=196) | -1.1 mg/dL | Standard Error 1.72 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (Low-Density Lipoprotein Cholesterol) | Week 42 (n=208; n=197) | -0.8 mg/dL | Standard Error 1.84 |
Secondary
Change From Baseline in Serum Lipids (Total Cholesterol)
The change in total cholesterol measured at each week indicated including final visit from baseline.
Time frame: Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.
Population: All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (Total Cholesterol) | Week 12 (n=213; n=201) | -4.2 mg/dL | Standard Error 2.06 |
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (Total Cholesterol) | Week 42 (n=213; n=201) | 0.2 mg/dL | Standard Error 2.07 |
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (Total Cholesterol) | Week 26 (n=213; n=201) | 1.6 mg/dL | Standard Error 2.03 |
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (Total Cholesterol) | Week 52 (n=213; n=201) | -0.8 mg/dL | Standard Error 2.28 |
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (Total Cholesterol) | Week 8 (n=208; n=195) | -5.6 mg/dL | Standard Error 2.01 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (Total Cholesterol) | Week 52 (n=213; n=201) | -0.5 mg/dL | Standard Error 2.35 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (Total Cholesterol) | Week 8 (n=208; n=195) | -1.6 mg/dL | Standard Error 2.08 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (Total Cholesterol) | Week 12 (n=213; n=201) | -0.7 mg/dL | Standard Error 2.12 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (Total Cholesterol) | Week 26 (n=213; n=201) | 0.1 mg/dL | Standard Error 2.09 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (Total Cholesterol) | Week 42 (n=213; n=201) | 0.1 mg/dL | Standard Error 2.13 |
Secondary
Change From Baseline in Serum Lipids (Triglycerides)
The change in triglycerides measured at each week indicated including final visit from baseline.
Time frame: Baseline, Week 8, Week 12, Week 26, Week 42 and Week 52.
Population: All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (Triglycerides) | Week 12 (n=213; n=201) | -15.5 mg/dL | Standard Error 5.72 |
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (Triglycerides) | Week 42 (n=213; n=201) | -12.6 mg/dL | Standard Error 5.01 |
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (Triglycerides) | Week 26 (n=213; n=201) | -16.3 mg/dL | Standard Error 4.74 |
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (Triglycerides) | Week 52 (n=213; n=201) | -13.2 mg/dL | Standard Error 5.27 |
| Alogliptin 25 mg QD | Change From Baseline in Serum Lipids (Triglycerides) | Week 8 (n=208; n=195) | -12.8 mg/dL | Standard Error 5.04 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (Triglycerides) | Week 52 (n=213; n=201) | 1.9 mg/dL | Standard Error 5.42 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (Triglycerides) | Week 8 (n=208; n=195) | 2.7 mg/dL | Standard Error 5.2 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (Triglycerides) | Week 12 (n=213; n=201) | 7.5 mg/dL | Standard Error 5.89 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (Triglycerides) | Week 26 (n=213; n=201) | 3.9 mg/dL | Standard Error 4.88 |
| Glipizide 5 mg QD | Change From Baseline in Serum Lipids (Triglycerides) | Week 42 (n=213; n=201) | 5.5 mg/dL | Standard Error 5.16 |
Secondary
Homeostasis Model Assessment of Beta Cell Function
The change between homeostasis model assessment of beta cell function collected at each week indicated including final visit relative to baseline. Homeostasis model assessment of beta cell function measures beta cell function, calculated by a constant (20) times insulin, divided by fasting plasma glucose minus a constant (3.5).
Time frame: Baseline, Week 12, Week 26, Week 42 and Week 52.
Population: All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Alogliptin 25 mg QD | Homeostasis Model Assessment of Beta Cell Function | Week 12 (n=203; n=184) | -6.104 percent score of beta cell function | Standard Error 8.3062 |
| Alogliptin 25 mg QD | Homeostasis Model Assessment of Beta Cell Function | Week 26 (n=207; n=193) | -0.136 percent score of beta cell function | Standard Error 9.7088 |
| Alogliptin 25 mg QD | Homeostasis Model Assessment of Beta Cell Function | Week 42 (n=207; n=193) | -5.571 percent score of beta cell function | Standard Error 7.1395 |
| Alogliptin 25 mg QD | Homeostasis Model Assessment of Beta Cell Function | Week 52 (n=207; n=193) | -9.755 percent score of beta cell function | Standard Error 13.8868 |
| Glipizide 5 mg QD | Homeostasis Model Assessment of Beta Cell Function | Week 52 (n=207; n=193) | 35.281 percent score of beta cell function | Standard Error 14.3836 |
| Glipizide 5 mg QD | Homeostasis Model Assessment of Beta Cell Function | Week 12 (n=203; n=184) | 30.081 percent score of beta cell function | Standard Error 8.7264 |
| Glipizide 5 mg QD | Homeostasis Model Assessment of Beta Cell Function | Week 42 (n=207; n=193) | 16.004 percent score of beta cell function | Standard Error 7.395 |
| Glipizide 5 mg QD | Homeostasis Model Assessment of Beta Cell Function | Week 26 (n=207; n=193) | 31.669 percent score of beta cell function | Standard Error 10.0562 |
Secondary
Incidence of Glycosylated Hemoglobin Decrease From Baseline.
The percentage of participants with a decrease from baseline in the percentage of glycosylated hemoglobin (the percentage of hemoglobin that is bound to glucose) greater than or equal to 0.5, 1.0, 1.5 and 2.0% during the 52 week study.
Time frame: Baseline and Week 52.
Population: All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin 25 mg QD | Incidence of Glycosylated Hemoglobin Decrease From Baseline. | Decrease from Baseline in HbA1c ≥0.5% | 32.1 percentage of participants |
| Alogliptin 25 mg QD | Incidence of Glycosylated Hemoglobin Decrease From Baseline. | Decrease from Baseline in HbA1c ≥1.0% | 12.6 percentage of participants |
| Alogliptin 25 mg QD | Incidence of Glycosylated Hemoglobin Decrease From Baseline. | Decrease from Baseline in HbA1c ≥1.5% | 5.1 percentage of participants |
| Alogliptin 25 mg QD | Incidence of Glycosylated Hemoglobin Decrease From Baseline. | Decrease from Baseline in HbA1c ≥2.0% | 2.8 percentage of participants |
| Glipizide 5 mg QD | Incidence of Glycosylated Hemoglobin Decrease From Baseline. | Decrease from Baseline in HbA1c ≥2.0% | 1.4 percentage of participants |
| Glipizide 5 mg QD | Incidence of Glycosylated Hemoglobin Decrease From Baseline. | Decrease from Baseline in HbA1c ≥0.5% | 29.0 percentage of participants |
| Glipizide 5 mg QD | Incidence of Glycosylated Hemoglobin Decrease From Baseline. | Decrease from Baseline in HbA1c ≥1.5% | 2.3 percentage of participants |
| Glipizide 5 mg QD | Incidence of Glycosylated Hemoglobin Decrease From Baseline. | Decrease from Baseline in HbA1c ≥1.0% | 10.3 percentage of participants |
Secondary
Incidence of Hyperglycemic Rescue
The number of participants requiring rescue for failing to achieve pre-specified glycemic targets during the 52 week study.
Time frame: On Occurrence (up to 52 weeks).
Population: All randomized participants who had at least 1 dose of study medication (full analysis set). Participants who discontinued prior to Week 2 were excluded from analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin 25 mg QD | Incidence of Hyperglycemic Rescue | Week 42 to Week 52 | 10 participants |
| Alogliptin 25 mg QD | Incidence of Hyperglycemic Rescue | Overall | 50 participants |
| Alogliptin 25 mg QD | Incidence of Hyperglycemic Rescue | Week 2 to <Week 4 | 1 participants |
| Alogliptin 25 mg QD | Incidence of Hyperglycemic Rescue | Week 4 to <Week 8 | 2 participants |
| Alogliptin 25 mg QD | Incidence of Hyperglycemic Rescue | Week 8 to <Week 12 | 1 participants |
| Alogliptin 25 mg QD | Incidence of Hyperglycemic Rescue | Week 12 to <Week 16 | 14 participants |
| Alogliptin 25 mg QD | Incidence of Hyperglycemic Rescue | Week 16 to <Week 20 | 6 participants |
| Alogliptin 25 mg QD | Incidence of Hyperglycemic Rescue | Week 20 to <Week 26 | 5 participants |
| Alogliptin 25 mg QD | Incidence of Hyperglycemic Rescue | Week 26 to <Week 34 | 10 participants |
| Alogliptin 25 mg QD | Incidence of Hyperglycemic Rescue | Week 34 to <Week 42 | 6 participants |
| Glipizide 5 mg QD | Incidence of Hyperglycemic Rescue | Week 20 to <Week 26 | 8 participants |
| Glipizide 5 mg QD | Incidence of Hyperglycemic Rescue | Week 42 to Week 52 | 6 participants |
| Glipizide 5 mg QD | Incidence of Hyperglycemic Rescue | Week 12 to <Week 16 | 14 participants |
| Glipizide 5 mg QD | Incidence of Hyperglycemic Rescue | Overall | 37 participants |
| Glipizide 5 mg QD | Incidence of Hyperglycemic Rescue | Week 34 to <Week 42 | 7 participants |
| Glipizide 5 mg QD | Incidence of Hyperglycemic Rescue | Week 2 to <Week 4 | 0 participants |
| Glipizide 5 mg QD | Incidence of Hyperglycemic Rescue | Week 16 to <Week 20 | 9 participants |
| Glipizide 5 mg QD | Incidence of Hyperglycemic Rescue | Week 4 to <Week 8 | 1 participants |
| Glipizide 5 mg QD | Incidence of Hyperglycemic Rescue | Week 26 to <Week 34 | 2 participants |
| Glipizide 5 mg QD | Incidence of Hyperglycemic Rescue | Week 8 to <Week 12 | 0 participants |
Secondary
Incidence of Hypoglycemia
Percentage of participants with at least one hypoglycemic episode during 52 week study.
Time frame: On occurrence (up to 52 weeks).
Population: Percentages based on the number of Safety Set participants in each treatment group.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Alogliptin 25 mg QD | Incidence of Hypoglycemia | 5.4 percentage of participants |
| Glipizide 5 mg QD | Incidence of Hypoglycemia | 26.0 percentage of participants |
Secondary
Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL).
The number of participants with a fasting plasma glucose value ≥ to 200 mg per dL during the 52 week study.
Time frame: On Occurrence (up to 52 weeks).
Population: All randomized participants who had at least 1 dose of study medication (full analysis set).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin 25 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Baseline to <Week 4 | 30 participants |
| Alogliptin 25 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Week 4 to <Week 8 | 11 participants |
| Alogliptin 25 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Week 8 to <Week 12 | 12 participants |
| Alogliptin 25 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Week 12 to <Week 16 | 11 participants |
| Alogliptin 25 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Week 16 to <Week 20 | 5 participants |
| Alogliptin 25 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Week 20 to <Week 26 | 2 participants |
| Alogliptin 25 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Week 26 to <Week 34 | 3 participants |
| Alogliptin 25 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Week 34 to <Week 42 | 2 participants |
| Alogliptin 25 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Week 42 to Week 52 | 9 participants |
| Alogliptin 25 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Overall | 50 participants |
| Glipizide 5 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Week 34 to <Week 42 | 4 participants |
| Glipizide 5 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Baseline to <Week 4 | 17 participants |
| Glipizide 5 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Week 20 to <Week 26 | 3 participants |
| Glipizide 5 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Week 4 to <Week 8 | 5 participants |
| Glipizide 5 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Overall | 37 participants |
| Glipizide 5 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Week 8 to <Week 12 | 8 participants |
| Glipizide 5 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Week 26 to <Week 34 | 8 participants |
| Glipizide 5 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Week 12 to <Week 16 | 8 participants |
| Glipizide 5 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Week 42 to Week 52 | 6 participants |
| Glipizide 5 mg QD | Incidence of Marked Hyperglycemia (Fasting Plasma Glucose ≥200 mg Per dL). | Week 16 to <Week 20 | 4 participants |
Secondary
Incidence of Subjects Achieving Glycosylated Hemoglobin <=7%
The percentage of participants with a value for the percentage of glycosylated hemoglobin (HbA1c; the percentage of hemoglobin that is bound to glucose) less than or equal to 6.5 and 7.0% during the 52 week study.
Time frame: Baseline and Week 52.
Population: All randomized participants who had at least 1 dose of study medication (full analysis set) with last observation carried forward.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alogliptin 25 mg QD | Incidence of Subjects Achieving Glycosylated Hemoglobin <=7% | HbA1c ≤6.5% | 22.3 percentage of participants |
| Alogliptin 25 mg QD | Incidence of Subjects Achieving Glycosylated Hemoglobin <=7% | HbA1c ≤7.0% | 48.8 percentage of participants |
| Glipizide 5 mg QD | Incidence of Subjects Achieving Glycosylated Hemoglobin <=7% | HbA1c ≤6.5% | 18.2 percentage of participants |
| Glipizide 5 mg QD | Incidence of Subjects Achieving Glycosylated Hemoglobin <=7% | HbA1c ≤7.0% | 45.3 percentage of participants |