Remission Evaluation of Metabolic Interventions in Type 2 Diabetes (REMIT Pilot Trial)

Study Overview
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Brief Summary
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The purpose of this pilot trial is to determine whether an intensive treatment with insulin glargine, metformin, acarbose and lifestyle can normalize blood glucose levels in patients with recently diagnosed type 2 diabetes mellitus when compared to standard diabetes care.

Detailed Description
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This is a pilot trial of 125 patients allocated to either usual care (1/3), 2 months or 4 months of intensive lifestyle and pharmacotherapy followed by cessation of all drug therapy.

Official Title
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Remission Evaluation of Metabolic Interventions in Type 2 Diabetes (REMIT): A Randomized Controlled Pilot Trial

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: insulin glargine
* Drug: metformin
* Drug: acarbose
* Behavioral: lifestyle therapy
* Drug: insulin glargine
* Drug: metformin
* Drug: acarbose
* Behavioral: lifestyle therapy
* Other: Standard glycemic care


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 3 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 ≤ 8.5% on no oral hypoglycemic agents or HbA1C ≤ 7.5% on 1 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 therapy history of hypoglycemia unawareness, or severe hypoglycemia requiring assistance 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 inflammatory bowel disease, colonic ulcers, recent or significant bowel surgery, or predisposition to bowel obstruction cardiovascular disease including any of: systolic blood pressure >180 mmHg or diastolic blood pressure >105 mmHg peripheral vascular disease left bundle branch block or third degree AV block tachyarrhythmias or bradyarrhythmias with uncontrolled ventricular rate stenotic valvular heart disease cardiomyopathy history of heart failure history of aortic dissection documented history of angina or coronary artery disease history of stroke or transient ischemic attack pulmonary disease with dependence on oxygen history of any disease requiring intermittent or 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 any history of excessive alcohol intake, acute or chronic known hypersensitivity to metformin, acarbose, or insulin glargine.

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: Group 1 (short)<br> | Drug: insulin glargine<br>* sc injection<br>Drug: metformin<br>* oral administration<br>Drug: acarbose<br>* oral administration<br>Behavioral: lifestyle therapy<br>* diet and exercise<br>|
| Experimental: Group 2 (long)<br> | Drug: insulin glargine<br>* sc injection<br>Drug: metformin<br>* oral administration<br>Drug: acarbose<br>* oral administration<br>Behavioral: lifestyle therapy<br>* diet and exercise<br>|
| Other: Standard care<br> | Other: Standard glycemic care<br>* as informed by the current clinical practice guidelines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Normoglycemia on Therapy | Percentage of participants achieving normoglycemia on therapy in the experimental group 1 compared to the control group. Percentage of participants achieving normoglycemia on therapy in the experimental group 2 compared to the control group. Normoglycemia on therapy is defined as a mean fasting capillary blood glucose </=5.4 mmol/L and a mean 2-hour pc blood glucose </=6.8 mmol/L on 2 seven-point glucose profiles. | (1) 8 weeks and (2) 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 1) Percentage of Participants With Normal Glucose Tolerance in the Experimental Group 1 Compared to the Control Group. 2) Percentage of Participants With Normal Glucose Tolerance in the Experimental Group 2 Compared to the Control Group. | Normal glucose tolerance is defined as a fasting plasma glucose <6.1 mmol/L and a 2-hour pc plasma glucose <7.8 mmol/L on a 75 g oral glucose tolerance test off diabetes drugs. | (1) 20 weeks and (2) 28 weeks | 
| Percentage of Participants With Normal Fasting Plasma Glucose | Normal fasting plasma glucose is defined as <6.1 mmol/L. | 52 weeks | 
| Change in Fasting Plasma Glucose From Baseline |  | Baseline and 52 weeks | 
| HbA1C |  | 8, 20, 28 and 52 weeks | 
| Change in Weight From Baseline |  | Baseline, 8, 20, 28 and 52 weeks | 
| Number of Participants With Symptomatic Hypoglycemic Episodes |  | 52 weeks | 
| Number of Participants With Severe Hypoglycemic Episodes |  | 52 weeks | 

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