Type 2 Diabetes
Conditions
Keywords
Type 2 Diabetes, Sitagliptin, Glimepiride, Elderly patients, Japanese
Brief summary
The purpose of this study is to compare the efficacy and the safety of sitagliptin and glimepiride in drug naïve elderly patients with Type 2 diabetes as evaluated by HbA1c change from baseline at 52 W as efficacy and incidence of hypoglycemia from randomization to 52 W as safety. The clinical hypotheses are non-inferiority of sitagliptin to glimepiride in efficacy as judged by HbA1c change from baseline at 52 W and superiority of sitagliptin to glimepiride in safety as judged by incidence of hypoglycemia in drug naïve elderly patients with T2DM. In addition, comparison of efficacy is extended to 104 W.
Interventions
DRUGSitagliptin
Starting dose for sitagliptin is 50mg per day, can be increased up to 100mg (25-50mg; estimate glomerular filtration rate (eGFR) 30=\< \<50).
DRUGGlimepiride
Starting dose for glimepiride is 0.5mg per day, can be increased up to 6.0mg
Sponsors
Merck Sharp & Dohme LLC
Japan Association for Diabetes Education and Care
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients with type 2 diabetes who are oral hypoglycemic agent naive or, α-glucosidase inhibitor or biguanide monotherapy (to be washed out 4 weeks prior to randomization) 2. Signed informed consent obtained before any trial-related activities 3. Treatment with diet and exercise for 12 weeks and longer at screening 4. Age =\>60 y.o. 5. Male and Female 6. HbA1c 6.9%=\< \<8.9%
Exclusion criteria
1. Active proliferative retinopathy or maculopathy requiring treatment 2. Liver dysfunction (\>x2 of upper normal limit), moderate or severe renal dysfunction(serum Cr\>1.5mg/dL in male, Cr\>1.3mg/dL in female, eGFR\<30), severe cardiac disease (NYHA III or IV), malignancy or uncontrolled hypertension (treated or untreated) as judged by the Investigator 3. Mental incapacity (including moderate or severe dementia) precluding adequate understanding and/or cooperation as judged by the Investigator 4. Recurrent hypoglycaemia or hypoglycaemic unawareness as judged by the investigator 5. Previous history of severe allergy to pharmaceutical products 6. Systemic glucocorticoids users or potential users 7. Suspected type 1 diabetes (including slowly progressive insulin dependent diabetes mellitus) or positive anti-glutamic acid decarboxylase antibody 8. Any condition that the investigator considers a potential obstacle to trial participation and/or data analysis
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change From Baseline in HbA1c at 52 W | Baseline and 52 W |
| Number of Participants With Hypoglycaemia | From baseline to 52 W |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Number of Participants Achieving HbA1c < 6.9 % | 52 W | — |
| Change From Baseline in HOMA-β at 52 W | Baseline and 52 W | β cell function is measured by the Homeostatic Model Assessment(HOMA-β). HOMA β = \[20 x fasting insulin (μU/mL)\] / \[fasting plasma glucose (mmol/L) - 3.5\] |
| Change From Baseline in Insulin/Proinsulin Ratio at 52 W | Baseline and 52 W | — |
| Change From Baseline in Body Weight at 52 W | Baseline and 52 W | — |
Countries
Japan
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin Starting dose for sitagliptin is 50mg per day, can be increased up to 100mg (25-50mg; eGFR 30=\< \<50). | 143 |
| Glimepiride Starting dose for glimepiride is 0.5mg per day, can be increased up to 6.0mg | 129 |
| Total | 272 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 8 | 6 |
| Overall Study | Death | 0 | 1 |
| Overall Study | Did not receive study drug | 5 | 9 |
| Overall Study | Lost to Follow-up | 14 | 7 |
| Overall Study | Nonparticipation in Extension Study | 39 | 50 |
| Overall Study | Physician Decision | 5 | 8 |
| Overall Study | Withdrawal by Subject | 6 | 11 |
Baseline characteristics
| Characteristic | Sitagliptin | Glimepiride | Total |
|---|---|---|---|
| Age, Continuous | 70.2 years STANDARD_DEVIATION 5.4 | 70.8 years STANDARD_DEVIATION 5.5 | 70.5 years STANDARD_DEVIATION 5.5 |
| BMI | 24.1 kg/m^2 STANDARD_DEVIATION 3.3 | 24.2 kg/m^2 STANDARD_DEVIATION 3.6 | 24.2 kg/m^2 STANDARD_DEVIATION 3.4 |
| Body weight | 60.9 kg STANDARD_DEVIATION 9.7 | 60.9 kg STANDARD_DEVIATION 9.7 | 60.9 kg STANDARD_DEVIATION 9.7 |
| eGFR | 68.8 mL/min/1.73m^2 STANDARD_DEVIATION 17.1 | 67.9 mL/min/1.73m^2 STANDARD_DEVIATION 17.1 | 68.4 mL/min/1.73m^2 STANDARD_DEVIATION 17.1 |
| HbA1c | 7.48 percent STANDARD_DEVIATION 0.68 | 7.49 percent STANDARD_DEVIATION 0.67 | 7.48 percent STANDARD_DEVIATION 0.67 |
| HOMA-β | 43.3 percent STANDARD_DEVIATION 33.7 | 38.5 percent STANDARD_DEVIATION 34 | 41.1 percent STANDARD_DEVIATION 33.9 |
| Insulin/Proinsulin Ratio | 0.217 ratio STANDARD_DEVIATION 0.122 | 0.205 ratio STANDARD_DEVIATION 0.129 | 0.211 ratio STANDARD_DEVIATION 0.125 |
| Region of Enrollment Japan | 143 participants | 129 participants | 272 participants |
| Sex: Female, Male Female | 69 Participants | 50 Participants | 119 Participants |
| Sex: Female, Male Male | 74 Participants | 79 Participants | 153 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 33 / 148 | 31 / 143 |
| serious Total, serious adverse events | 13 / 148 | 3 / 143 |
Outcome results
Primary
Change From Baseline in HbA1c at 52 W
Time frame: Baseline and 52 W
Population: Analysis set of evaluation for efficacy; Per Protocol Set.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin | Change From Baseline in HbA1c at 52 W | -0.66 percent |
| Glimepiride | Change From Baseline in HbA1c at 52 W | -0.77 percent |
p-value: 0.08795% CI: [-0.02, 0.24]ANCOVA
Primary
Number of Participants With Hypoglycaemia
Time frame: From baseline to 52 W
Population: Analysis set of evaluation for safety.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sitagliptin | Number of Participants With Hypoglycaemia | 7 Participants |
| Glimepiride | Number of Participants With Hypoglycaemia | 23 Participants |
p-value: 0.002Fisher Exact
Secondary
Change From Baseline in Body Weight at 52 W
Time frame: Baseline and 52 W
Population: Analysis set of evaluation for efficacy; Per Protocol Set. Some participants had loss of the measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Body Weight at 52 W | -0.367 kg | Standard Deviation 2.441 |
| Glimepiride | Change From Baseline in Body Weight at 52 W | 0.309 kg | Standard Deviation 2.915 |
p-value: 0.043ANCOVA
Secondary
Change From Baseline in HOMA-β at 52 W
β cell function is measured by the Homeostatic Model Assessment(HOMA-β). HOMA β = \[20 x fasting insulin (μU/mL)\] / \[fasting plasma glucose (mmol/L) - 3.5\]
Time frame: Baseline and 52 W
Population: Analysis set of evaluation for efficacy; Per Protocol Set. Some participants had loss of the measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in HOMA-β at 52 W | 10.2 percent | Standard Deviation 35.7 |
| Glimepiride | Change From Baseline in HOMA-β at 52 W | 23.7 percent | Standard Deviation 56.1 |
p-value: 0.03ANCOVA
Secondary
Change From Baseline in Insulin/Proinsulin Ratio at 52 W
Time frame: Baseline and 52 W
Population: Analysis set of evaluation for efficacy; Per Protocol Set. Some participants had loss of the measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change From Baseline in Insulin/Proinsulin Ratio at 52 W | -0.049 ratio | Standard Deviation 0.111 |
| Glimepiride | Change From Baseline in Insulin/Proinsulin Ratio at 52 W | -0.002 ratio | Standard Deviation 0.095 |
p-value: <0.001ANCOVA
Secondary
The Number of Participants Achieving HbA1c < 6.9 %
Time frame: 52 W
Population: Analysis set of evaluation for efficacy; Per Protocol Set Some participants were not completed to 52 W.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sitagliptin | The Number of Participants Achieving HbA1c < 6.9 % | 89 Participants |
| Glimepiride | The Number of Participants Achieving HbA1c < 6.9 % | 86 Participants |
p-value: 1Fisher Exact