Type 2 Diabetes Mellitus
Conditions
Keywords
Diabetes, Insulin, Glargine, Metformin, Sitagliptin, Diet, Excercise, Lifestyle
Brief summary
The purpose of the study is to determine whether in patients with early type 2 diabetes,a short-term intensive metabolic intervention comprising of sitagliptin, metformin, basal insulin glargine and lifestyle approaches will be superior to standard diabetes therapy in achieving sustained diabetes remission.
Detailed description
This is a multicentre, open-label, randomized controlled trial in 100 patients with recently-diagnosed T2DM. Participants will be randomized to 2 treatment groups: (a) a 12-week course of treatment with sitagliptin, metformin, insulin glargine and lifestyle therapy, or (b) standard diabetes therapy, and followed for a total of 64 weeks (1 year and 3 months). In all participants with HbA1C \< 7.3% at the 12 week visit, glucose-lowering medications will be discontinued and participants will be encouraged to continue with lifestyle modifications and regular glucose monitoring. Participants with HbA1C ≥ 7.3% at this visit or who meet criteria for hyperglycemic relapse after stopping drugs will receive standard glycemic management as informed by the current Canadian Diabetes Association clinical practice guidelines
Interventions
DRUGinsulin glargine
Dose is titrated to achieve fasting normoglycemia
Dose is titrated to 50/1000 mg bid or maximal tolerated dose
BEHAVIORALlifestyle therapy
Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving
Sponsors
Merck Sharp & Dohme LLC
Population Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. men and women 30-80 years of age inclusive; 2. type 2 diabetes mellitus diagnosed by a physician within 5 years prior to patient enrollment; 3. anti-diabetic drug regimen (either drug or dose of drug) unchanged during 8 weeks prior to screening and randomization; 4. HbA1C ≤ 9.5% on no oral hypoglycemic agents or HbA1C ≤ 8.0% on 1 oral agent or on half-maximal doses of 2 agents; 5. body mass index ≥ 23 kg/m2; 6. a negative pregnancy test and an agreement to use a reliable method of birth control for the duration of the trial in all females with childbearing potential; 7. ability and willingness to perform self-monitoring of capillary blood glucose (SMBG); ability and willingness to self-inject insulin; 8. provision of informed consent.
Exclusion criteria
1. current use of insulin; 2. history of hypoglycemia unawareness; history of severe hypoglycemia requiring assistance within the last 5 years; 3. renal dysfunction as evidenced by serum creatinine (Cr) ≥ 124 μmol/l; 4. history of lactic acidosis or diabetic ketoacidosis; 5. active liver disease or elevated alanine transferase (ALT) levels ≥ 2.5 times upper limit of normal at the time of enrollment; 6. history of pancreatitis; 7. cardiovascular disease including any of: a) systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 105 mmHg; b) peripheral vascular disease; c) left bundle branch block or second or third degree AV block; d) tachyarrhythmias or bradyarrhythmias with uncontrolled ventricular rate; e) stenotic valvular heart disease; f) cardiomyopathy; g) history of heart failure; h) history of aortic dissection; i) documented history of angina or coronary artery disease; j) history of stroke or transient ischemic attack; 8. history of any disease requiring continuous systemic glucocorticoid treatment; 9. history of any major illness with a life expectancy of \< 3 years; 10. history of injury or any other condition that significantly limits participant's ability to achieve moderate levels of physical activity; 11. excessive alcohol consumption (\>14 alcoholic drinks per week in men and \>7 alcoholic drinks per week in women); 12. known hypersensitivity to insulin glargine, metformin, or any DPP-4 inhibitor.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Hyperglycemia Relapse in the Experimental Group Compared to the Control Group | 64 weeks of follow-up | Hyperglycemia relapse for primary outcome was defined as any one of: 1. Capillary glucose \>10 mmol/L on \>/=50% of readings over 1 week; 2. HbA1C \>/=6.5%; 3. use of diabetes drugs; 4. fasting plasma glucose \>/= 7.0 mmol/L; 5. 2-hour postprandial plasma glucose \>/=11.1 mmol/L on an oral glucose tolerance test. |
| Number of Participants With Severe Hypoglycemic Episodes | 64 weeks of follow-up | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Achieving Drug-free Diabetes Remission | 24 weeks after randomization | Diabetes remission is defined as absence of hyperglycemia relapse |
| Number of Participants With Drug-free Normal Glucose Tolerance | 24 weeks after randomization | Normal glucose tolerance is defined as a FPG\<6.1 mmol/L and a 2-hour plasma glucose \<7.8 mmol/L on a 75 g oral glucose tolerance test |
| Percent Change in Weight | Baseline and 12 weeks after randomization | — |
| Change in Waist Circumference | Baseline and 12 weeks after randomization | — |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intervention Drug: insulin glargine - sc injection Drug: sitagliptin/metformin - oral administration Behavioral: lifestyle therapy
insulin glargine: Dose is titrated to achieve fasting normoglycemia
sitagliptin/metformin: Dose is titrated to 50/1000 mg bid or maximal tolerated dose
lifestyle therapy: Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving | 50 |
| Standard Care Standard glycemic care as informed by the current clinical practice guidelines | 52 |
| Total | 102 |
Baseline characteristics
| Characteristic | Intervention | Standard Care | Total |
|---|---|---|---|
| Age, Continuous | 56.4 years STANDARD_DEVIATION 8.7 | 54.7 years STANDARD_DEVIATION 9.3 | 55.5 years STANDARD_DEVIATION 9 |
| Race/Ethnicity, Customized Caucasian | 42 Participants | 47 Participants | 89 Participants |
| Race/Ethnicity, Customized Non-Caucasian | 8 Participants | 5 Participants | 13 Participants |
| Region of Enrollment Canada | 50 participants | 52 participants | 102 participants |
| Sex: Female, Male Female | 18 Participants | 20 Participants | 38 Participants |
| Sex: Female, Male Male | 32 Participants | 32 Participants | 64 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 50 | 0 / 52 |
| other Total, other adverse events | 9 / 50 | 4 / 52 |
| serious Total, serious adverse events | 0 / 50 | 0 / 52 |
Outcome results
Primary
Number of Participants With Hyperglycemia Relapse in the Experimental Group Compared to the Control Group
Hyperglycemia relapse for primary outcome was defined as any one of: 1. Capillary glucose \>10 mmol/L on \>/=50% of readings over 1 week; 2. HbA1C \>/=6.5%; 3. use of diabetes drugs; 4. fasting plasma glucose \>/= 7.0 mmol/L; 5. 2-hour postprandial plasma glucose \>/=11.1 mmol/L on an oral glucose tolerance test.
Time frame: 64 weeks of follow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Number of Participants With Hyperglycemia Relapse in the Experimental Group Compared to the Control Group | 41 Participants |
| Standard Care | Number of Participants With Hyperglycemia Relapse in the Experimental Group Compared to the Control Group | 48 Participants |
Primary
Number of Participants With Severe Hypoglycemic Episodes
Time frame: 64 weeks of follow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Number of Participants With Severe Hypoglycemic Episodes | 0 Participants |
| Standard Care | Number of Participants With Severe Hypoglycemic Episodes | 0 Participants |
Secondary
Change in Waist Circumference
Time frame: Baseline and 12 weeks after randomization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Change in Waist Circumference | -2.3 cm | Standard Deviation 3.5 |
| Standard Care | Change in Waist Circumference | -1.8 cm | Standard Deviation 4.8 |
Secondary
Number of Participants Achieving Drug-free Diabetes Remission
Diabetes remission is defined as absence of hyperglycemia relapse
Time frame: 24 weeks after randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Number of Participants Achieving Drug-free Diabetes Remission | 8 Participants |
| Standard Care | Number of Participants Achieving Drug-free Diabetes Remission | 4 Participants |
Secondary
Number of Participants With Drug-free Normal Glucose Tolerance
Normal glucose tolerance is defined as a FPG\<6.1 mmol/L and a 2-hour plasma glucose \<7.8 mmol/L on a 75 g oral glucose tolerance test
Time frame: 24 weeks after randomization
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Intervention | Number of Participants With Drug-free Normal Glucose Tolerance | 3 Participants |
| Standard Care | Number of Participants With Drug-free Normal Glucose Tolerance | 1 Participants |
Secondary
Percent Change in Weight
Time frame: Baseline and 12 weeks after randomization
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intervention | Percent Change in Weight | -2.1 % change | Standard Deviation 2.5 |
| Standard Care | Percent Change in Weight | -1.4 % change | Standard Deviation 2.9 |