An Open-label, Randomized, Parallel Design Trial to Compare the Efficacy of a Sitagliptin-based Metabolic Intervention Versus Standard Diabetes Therapy in Inducing Remission of Type 2 Diabetes
Overview
- Phase
- Phase 3
- Intervention
- insulin glargine
- Conditions
- Type 2 Diabetes Mellitus
- Sponsor
- Population Health Research Institute
- Enrollment
- 102
- Locations
- 6
- Primary Endpoint
- Number of Participants With Severe Hypoglycemic Episodes
- Status
- Completed
- Last Updated
- 4 years ago
Overview
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
Investigators
Eligibility Criteria
Inclusion Criteria
- •men and women 30-80 years of age inclusive;
- •type 2 diabetes mellitus diagnosed by a physician within 5 years prior to patient enrollment;
- •anti-diabetic drug regimen (either drug or dose of drug) unchanged during 8 weeks prior to screening and randomization;
- •HbA1C ≤ 9.5% on no oral hypoglycemic agents or HbA1C ≤ 8.0% on 1 oral agent or on half-maximal doses of 2 agents;
- •body mass index ≥ 23 kg/m2;
- •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;
- •ability and willingness to perform self-monitoring of capillary blood glucose (SMBG); ability and willingness to self-inject insulin;
- •provision of informed consent.
Exclusion Criteria
- •current use of insulin;
- •history of hypoglycemia unawareness; history of severe hypoglycemia requiring assistance within the last 5 years;
- •renal dysfunction as evidenced by serum creatinine (Cr) ≥ 124 μmol/l;
- •history of lactic acidosis or diabetic ketoacidosis;
- •active liver disease or elevated alanine transferase (ALT) levels ≥ 2.5 times upper limit of normal at the time of enrollment;
- •history of pancreatitis;
- •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;
- •history of any disease requiring continuous systemic glucocorticoid treatment;
- •history of any major illness with a life expectancy of \< 3 years;
- •history of injury or any other condition that significantly limits participant's ability to achieve moderate levels of physical activity;
Arms & Interventions
Intervention
Drug: insulin glargine - sc injection Drug: sitagliptin/metformin - oral administration Behavioral: lifestyle therapy
Intervention: insulin glargine
Intervention
Drug: insulin glargine - sc injection Drug: sitagliptin/metformin - oral administration Behavioral: lifestyle therapy
Intervention: sitagliptin/metformin
Intervention
Drug: insulin glargine - sc injection Drug: sitagliptin/metformin - oral administration Behavioral: lifestyle therapy
Intervention: lifestyle therapy
Outcomes
Primary Outcomes
Number of Participants With Severe Hypoglycemic Episodes
Time Frame: 64 weeks of follow-up
Number of Participants With Hyperglycemia Relapse in the Experimental Group Compared to the Control Group
Time Frame: 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.
Secondary Outcomes
- Number of Participants Achieving Drug-free Diabetes Remission(24 weeks after randomization)
- Change in Waist Circumference(Baseline and 12 weeks after randomization)
- Percent Change in Weight(Baseline and 12 weeks after randomization)
- Number of Participants With Drug-free Normal Glucose Tolerance(24 weeks after randomization)