Diabetes Mellitus, Type 2, End-Stage Kidney Disease
Conditions
Brief summary
The purpose of the study is to compare sitagliptin and glipizide in lowering blood sugar in participants with type-2 diabetes mellitus (T2DM) and end-stage renal disease on dialysis who do not have adequate glycemic control.
Interventions
DRUGSitagliptin
25 mg (one 25-mg tablet) once daily
DRUGGlipizide
2.5 mg (1/2 of a 5-mg tablet) once daily, up to 10 mg twice daily (four 5-mg tablets), for a maximum of 20 mg
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
30 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant has T2DM. * Participant is on dialysis on day of signing informed consent. * Participant is unlikely to conceive or uses acceptable methods of birth control: hormonal contraceptive, intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, or vasectomy. * Participant has hemoglobin A1c ≥7% and ≤9% measured at or within 2 weeks prior to Visit 4/Week -2. * Participant is ≥85% compliant with study medication during the single-blind placebo run-in (as determined by tablet/capsule count) and compliant with diet, exercise and other run-in treatments during the run-in period.
Exclusion criteria
* Participant has a history of type 1 diabetes mellitus or a history of ketoacidosis. * Participant is losing weight in a weight loss program and is not in the maintenance phase (defined as \<2 kg weight loss in 2 months), or intends to be involved in weight loss intervention outside that prescribed by the study. * Participant has a clinically significant hematological disorder (e.g., aplastic anemia, myeloproliferative or myelodysplastic syndromes, thrombocytopenia). * Participant has cirrhosis or active liver disease. * Participant has been on dialysis for \< 6 months. * Participant has been diagnosed with a significant cardiovascular disorder and has new or worsening signs or symptoms of congestive heart failure within 3 months of signing informed consent. * Participant has severe active peripheral vascular disease. * Participant has a history of malignancy ≤ 5 years prior to signing informed consent, or \> 5 years without documentation of remission/cure. * Participant is under treatment for hyperthyroidism. * Participant has a hypersensitivity or contraindication to glipizide.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c After Sitagliptin Treatment | Baseline / Week 54 | Change from baseline in mean hemoglobin A1c after treatment with sitagliptin for 54 weeks. Hemoglobin A1c is the percent of hemoglobin that is glycated. Results for the glipizide arm are not reported in this table because the primary outcome measure is for the sitagliptin arm only. |
| Number of Participants With Clinical Adverse Events | 54 Week Treatment Period + 28 days | Reported experiences assessed by investigators as adverse events, excluding data after initiation of glycemic rescue therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Symptomatic Hypoglycemic Adverse Events | 54 Week Treatment Period + 28 days | A symptomatic hypoglycemic adverse event is an episode with clinical symptoms attributed to hypoglycemia, without regard to fingerstick glucose level. |
| Change From Baseline in Fasting Plasma Glucose (FPG) | Baseline / Week 54 | Change from baseline in mean Fasting Plasma Glucose after treatment with sitagliptin versus glipizide for 54 weeks. |
| Change From Baseline in Hemoglobin A1c for Sitagliptin Versus Glipizide Treatment | Baseline / Week 54 | Change from baseline in least square means hemoglobin A1c after treatment with sitagliptin versus glipizide for 54 weeks. Hemoglobin A1c is the percent of hemoglobin that is glycated. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin 25 mg One 25 mg tablet once daily for 54 weeks | 64 |
| Glipizide 2.5 mg - 20 mg Between 2.5 mg - 20 mg daily for 54 weeks | 65 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 7 | 9 |
| Overall Study | Excluded Medication | 1 | 1 |
| Overall Study | Protocol Violation | 3 | 0 |
| Overall Study | Scheduled Kidney Transplant | 1 | 0 |
| Overall Study | Withdrawal by Subject | 5 | 10 |
Baseline characteristics
| Characteristic | Sitagliptin 25 mg | Glipizide 2.5 mg - 20 mg | Total |
|---|---|---|---|
| Age, Continuous | 60.5 years STANDARD_DEVIATION 9.1 | 58.5 years STANDARD_DEVIATION 9.9 | 59.5 years STANDARD_DEVIATION 9.5 |
| Sex: Female, Male Female | 24 Participants | 28 Participants | 52 Participants |
| Sex: Female, Male Male | 40 Participants | 37 Participants | 77 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 64 | 37 / 65 |
| serious Total, serious adverse events | 23 / 64 | 22 / 65 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c After Sitagliptin Treatment
Change from baseline in mean hemoglobin A1c after treatment with sitagliptin for 54 weeks. Hemoglobin A1c is the percent of hemoglobin that is glycated. Results for the glipizide arm are not reported in this table because the primary outcome measure is for the sitagliptin arm only.
Time frame: Baseline / Week 54
Population: Randomized participants. Numbers analyzed excluded participants with either no baseline or no post-baseline measurements. The last observation carried forward (LOCF) method was used to impute missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin 25 mg | Change From Baseline in Hemoglobin A1c After Sitagliptin Treatment | Change from Baseline at Week 54 | -0.74 Percent hemoglobin A1c | Standard Deviation 0.95 |
| Sitagliptin 25 mg | Change From Baseline in Hemoglobin A1c After Sitagliptin Treatment | Baseline | 7.89 Percent hemoglobin A1c | Standard Deviation 0.74 |
| Sitagliptin 25 mg | Change From Baseline in Hemoglobin A1c After Sitagliptin Treatment | Week 54 | 7.15 Percent hemoglobin A1c | Standard Deviation 0.98 |
Comparison: Model terms: treatment, prior diabetes pharmacotherapy (not on oral antihyperglycemic agent, or on oral antihyperglycemic agent), and a covariate for baseline A1c.p-value: <0.001ANCOVA
Primary
Number of Participants With Clinical Adverse Events
Reported experiences assessed by investigators as adverse events, excluding data after initiation of glycemic rescue therapy.
Time frame: 54 Week Treatment Period + 28 days
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin 25 mg | Number of Participants With Clinical Adverse Events | 53 Participants |
| Glipizide 2.5 mg - 20 mg | Number of Participants With Clinical Adverse Events | 52 Participants |
95% CI: [-10.9, 16.5]
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG)
Change from baseline in mean Fasting Plasma Glucose after treatment with sitagliptin versus glipizide for 54 weeks.
Time frame: Baseline / Week 54
Population: Randomized participants. Numbers analyzed excluded participants with no baseline or no post-baseline measurements. The last observation carried forward (LOCF) method was used to impute missing values.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin 25 mg | Change From Baseline in Fasting Plasma Glucose (FPG) | Baseline | 160.3 mg/dL | Standard Deviation 48.5 |
| Sitagliptin 25 mg | Change From Baseline in Fasting Plasma Glucose (FPG) | Week 54 | 135.8 mg/dL | Standard Deviation 40.4 |
| Sitagliptin 25 mg | Change From Baseline in Fasting Plasma Glucose (FPG) | Change from Baseline to Week 54 | -24.5 mg/dL | Standard Deviation 47.5 |
| Glipizide 2.5 mg - 20 mg | Change From Baseline in Fasting Plasma Glucose (FPG) | Baseline | 167.0 mg/dL | Standard Deviation 56.2 |
| Glipizide 2.5 mg - 20 mg | Change From Baseline in Fasting Plasma Glucose (FPG) | Week 54 | 134.0 mg/dL | Standard Deviation 58.2 |
| Glipizide 2.5 mg - 20 mg | Change From Baseline in Fasting Plasma Glucose (FPG) | Change from Baseline to Week 54 | -33.0 mg/dL | Standard Deviation 55.9 |
Comparison: Model terms: treatment, prior diabetes pharmacotherapy (not on oral antihyperglycemic agent, or on oral antihyperglycemic agent), and a covariate for baseline FPG.p-value: <0.00195% CI: [-38, -15.3]ANCOVA
Comparison: Model terms: treatment, prior diabetes pharmacotherapy (not on oral antihyperglycemic agent, or on oral antihyperglycemic agent), and a covariate for baseline FPG.p-value: <0.00195% CI: [-42.6, -19.9]ANCOVA
Comparison: Model terms: treatment, prior diabetes pharmacotherapy (not on oral antihyperglycemic agent, or on oral antihyperglycemic agent), and a covariate for baseline FPG.95% CI: [-11.5, 20.7]
Secondary
Change From Baseline in Hemoglobin A1c for Sitagliptin Versus Glipizide Treatment
Change from baseline in least square means hemoglobin A1c after treatment with sitagliptin versus glipizide for 54 weeks. Hemoglobin A1c is the percent of hemoglobin that is glycated.
Time frame: Baseline / Week 54
Population: Randomized participants. Numbers analyzed excluded participants with either no baseline or no post-baseline measurements. The last observation carried forward (LOCF) method was used to impute missing values.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin 25 mg | Change From Baseline in Hemoglobin A1c for Sitagliptin Versus Glipizide Treatment | -0.72 Percent hemoglobin A1c |
| Glipizide 2.5 mg - 20 mg | Change From Baseline in Hemoglobin A1c for Sitagliptin Versus Glipizide Treatment | -0.87 Percent hemoglobin A1c |
Comparison: Model terms: treatment, prior diabetes pharmacotherapy (not on oral antihyperglycemic agent, or on oral antihyperglycemic agent), and a covariate for baseline A1c.95% CI: [-0.18, 0.49]ANCOVA
Secondary
Number of Participants With Symptomatic Hypoglycemic Adverse Events
A symptomatic hypoglycemic adverse event is an episode with clinical symptoms attributed to hypoglycemia, without regard to fingerstick glucose level.
Time frame: 54 Week Treatment Period + 28 days
Population: All randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin 25 mg | Number of Participants With Symptomatic Hypoglycemic Adverse Events | 4 Participants |
| Glipizide 2.5 mg - 20 mg | Number of Participants With Symptomatic Hypoglycemic Adverse Events | 7 Participants |
p-value: 0.33695% CI: [-15.7, 5.6]Miettinen & Nurminen