Diabetes Mellitus, Type 2, Renal Insufficiency, Chronic
Conditions
Brief summary
The purpose of the study is to compare how sitagliptin and glipizide lower blood glucose levels in participants with moderate or severe renal insufficiency.
Interventions
DRUGSitagliptin
Participants with moderate renal insufficiency will receive two sitagliptin 25 mg tablets orally daily; participants with severe renal insufficiency will receive one sitagliptin 25 mg tablet orally daily
DRUGGlipizide
Participants will receive glipizide 2.5 mg (1/2 tablet) orally once daily up to 20 mg orally daily (10 mg twice daily)
Participants with moderate renal insufficiency will receive 2 placebo for sitagliptin tablets orally daily; participants with severe renal insufficiency will receive 1 placebo for sitagliptin tablet orally daily
DRUGPlacebo for Glipizide
Participants will receive 1/2 tablet of placebo for glipizide orally once daily up to 2 tablets orally twice daily
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has type 2 diabetes mellitus * Has moderate or severe renal insufficiency
Exclusion criteria
* Has type 1 diabetes mellitus or a history of ketoacidosis * Is on a new weight loss program * Has active liver disease * Is on dialysis or is likely to need dialysis during the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c (A1C) Levels at Week 54 | Baseline to Week 54 | A1C represents percentage of glycosylated hemoglobin. |
| Percentage of Participants With Hypoglycemic Events | Baseline up to 28 days following the last dose of study therapy | Percentage of participants with at least one symptomatic hypoglycemic adverse event, excluding data after initiation of glycemic rescue therapy. |
Secondary
| Measure | Time frame |
|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 54 | Baseline to Week 54 |
| Change From Baseline in Body Weight at Week 54 | Baseline to Week 54 |
Participant flow
Pre-assignment details
One site was identified as non-compliant with some of the requirements of Good Clinical Practice. For this reason, data from the 3 participants randomized at this site were deemed unreliable and were removed from all analyses.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin Participants randomized to 25 or 50 mg of sitagliptin orally daily + placebo for glipizide | 211 |
| Glipizide Participants randomized to glipizide 2.5 to 20 mg orally daily + placebo for sitagliptin | 212 |
| Total | 423 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 16 | 18 |
| Overall Study | Lack of Efficacy | 1 | 0 |
| Overall Study | Lost to Follow-up | 1 | 6 |
| Overall Study | Other | 2 | 2 |
| Overall Study | Physician Decision | 1 | 3 |
| Overall Study | Protocol Violation | 2 | 2 |
| Overall Study | Withdrawal by Subject | 24 | 11 |
Baseline characteristics
| Characteristic | Sitagliptin | Glipizide | Total |
|---|---|---|---|
| Age, Continuous | 64.2 years STANDARD_DEVIATION 10.7 | 64.2 years STANDARD_DEVIATION 9.4 | 64.2 years STANDARD_DEVIATION 10.1 |
| Sex: Female, Male Female | 80 Participants | 90 Participants | 170 Participants |
| Sex: Female, Male Male | 131 Participants | 122 Participants | 253 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 69 / 210 | 89 / 212 |
| serious Total, serious adverse events | 36 / 210 | 38 / 212 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c (A1C) Levels at Week 54
A1C represents percentage of glycosylated hemoglobin.
Time frame: Baseline to Week 54
Population: The per protocol population required that a participant had measurements both at baseline and at Week 54, and did not have any major protocol violations (e.g. drug compliance \<75%, addition of prohibited antihyperglycemic agent, or incorrect double-blind study medication). No missing data were imputed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin | Change From Baseline in Hemoglobin A1c (A1C) Levels at Week 54 | Baseline | 7.76 Percent of glycosylated hemoglobin | Standard Deviation 0.65 |
| Sitagliptin | Change From Baseline in Hemoglobin A1c (A1C) Levels at Week 54 | Change from Baseline at Week 54 | -0.70 Percent of glycosylated hemoglobin | Standard Deviation 0.8 |
| Glipizide | Change From Baseline in Hemoglobin A1c (A1C) Levels at Week 54 | Baseline | 7.79 Percent of glycosylated hemoglobin | Standard Deviation 0.7 |
| Glipizide | Change From Baseline in Hemoglobin A1c (A1C) Levels at Week 54 | Change from Baseline at Week 54 | -0.62 Percent of glycosylated hemoglobin | Standard Deviation 0.91 |
95% CI: [-0.29, 0.06]ANCOVA
Primary
Percentage of Participants With Hypoglycemic Events
Percentage of participants with at least one symptomatic hypoglycemic adverse event, excluding data after initiation of glycemic rescue therapy.
Time frame: Baseline up to 28 days following the last dose of study therapy
Population: All participants as treated (APaT) population included all randomized participants who took at least one dose of study therapy.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentage of Participants With Hypoglycemic Events | 6.2 percentage of participants |
| Glipizide | Percentage of Participants With Hypoglycemic Events | 17.0 percentage of participants |
p-value: 0.00195% CI: [-17.1, -4.8]Miettirnen& Nurminen method
Secondary
Change From Baseline in Body Weight at Week 54
Time frame: Baseline to Week 54
Population: All participants as treated (APaT) population included participants who had both baseline and Week 54 data (excluding data after initiation of glycemic rescue therapy).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Body Weight at Week 54 | -0.6 kg | Standard Error 0.3 |
| Glipizide | Change From Baseline in Body Weight at Week 54 | 1.2 kg | Standard Error 0.3 |
p-value: <0.00195% CI: [-2.6, -1]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 54
Time frame: Baseline to Week 54
Population: The per protocol population required that a participant had measurements both at baseline and at Week 54, and did not have any major protocol violations (e.g. drug compliance \<75%, addition of prohibited antihyperglycemic agent, or incorrect double-blind study medication). No missing data were imputed.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 54 | Baseline | 148.6 mg/dL | Standard Deviation 39.9 |
| Sitagliptin | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 54 | Change from Baseline at Week 54 | -16.7 mg/dL | Standard Deviation 47.1 |
| Glipizide | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 54 | Baseline | 143.9 mg/dL | Standard Deviation 35.7 |
| Glipizide | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 54 | Change from Baseline at Week 54 | -20.2 mg/dL | Standard Deviation 48.6 |
95% CI: [-1.9, 16.1]ANCOVA