Remission Evaluation of a Metabolic Intervention in Type 2 Diabetes With Sitagliptin (REMIT-Sita)

Study Overview
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Brief Summary
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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
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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

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: insulin glargine
* Drug: sitagliptin/metformin
* Behavioral: lifestyle therapy


Participation Criteria
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Eligibility Criteria
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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; excessive alcohol consumption (>14 alcoholic drinks per week in men and >7 alcoholic drinks per week in women); known hypersensitivity to insulin glargine, metformin, or any DPP-4 inhibitor.

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Drug: insulin glargine - sc injection Drug: sitagliptin/metformin - oral administration Behavioral: lifestyle therapy | Drug: insulin glargine<br>* Dose is titrated to achieve fasting normoglycemia<br>* Other names: Lantus;Drug: sitagliptin/metformin<br>* Dose is titrated to 50/1000 mg bid or maximal tolerated dose<br>* Other names: Janumet;Behavioral: lifestyle therapy<br>* Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving<br>* Other names: diet and exercise;|
| No Intervention: Standard Care<br>Standard glycemic care as informed by the current clinical practice guidelines | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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: Capillary glucose >10 mmol/L on >/=50% of readings over 1 week; HbA1C >/=6.5%; use of diabetes drugs; fasting plasma glucose >/= 7.0 mmol/L; 2-hour postprandial plasma glucose >/=11.1 mmol/L on an oral glucose tolerance test. | 64 weeks of follow-up | 
| Number of Participants With Severe Hypoglycemic Episodes |  | 64 weeks of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Achieving Drug-free Diabetes Remission | Diabetes remission is defined as absence of hyperglycemia relapse | 24 weeks after randomization | 
| 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 | 24 weeks after randomization | 
| Percent Change in Weight |  | Baseline and 12 weeks after randomization | 
| Change in Waist Circumference |  | Baseline and 12 weeks after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin, Diet, Diabetes, Glargine, Metformin, Sitagliptin, Excercise, Lifestyle