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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: insulin glargine; Drug: metformin; Drug: acarbose; Behavioral: lifestyle therapy; Other: Standard glycemic care

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 83
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • McMaster University Medical Centre, Diabetes Care and Research Program

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. men and women 30-80 years of age inclusive
2. type 2 diabetes mellitus diagnosed by a physician within 3 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 ≤ 8.5% on no oral hypoglycemic agents or HbA1C ≤ 7.5% on 1 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)
8. ability and willingness to self-inject insulin
9. provision of informed consent.

Exclusion Criteria:

1. current use of insulin therapy
2. history of hypoglycemia unawareness, or severe hypoglycemia requiring assistance
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 inflammatory bowel disease, colonic ulcers, recent or significant bowel surgery, or predisposition to bowel obstruction

7. 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
8. pulmonary disease with dependence on oxygen
9. history of any disease requiring intermittent or continuous systemic glucocorticoid treatment
10. history of any major illness with a life expectancy of <3 years
11. history of injury or any other condition that significantly limits participant's ability to achieve moderate levels of physical activity
12. any history of excessive alcohol intake, acute or chronic
13. known hypersensitivity to metformin, acarbose, or insulin glargine.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: Standard care	Other: Standard glycemic care; as informed by the current clinical practice guidelines
EXPERIMENTAL: Group 1 (short)	Drug: insulin glargine; sc injection; Drug: metformin; oral administration; Drug: acarbose; oral administration; Behavioral: lifestyle therapy; diet and exercise
EXPERIMENTAL: Group 2 (long)	Drug: insulin glargine; sc injection; Drug: metformin; oral administration; Drug: acarbose; oral administration; Behavioral: lifestyle therapy; diet and exercise

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Collaborators: Hamilton Health Sciences Corporation
• Investigators: Principal Investigator: Hertzel Gerstein, MD, Population Health Research Institute; Principal Investigator: Natalia McInnes (nee Yakubovich), MD, Population Health Research Institute

Publications and helpful links

General Publications

• McInnes N, Smith A, Otto R, Vandermey J, Punthakee Z, Sherifali D, Balasubramanian K, Hall S, Gerstein HC. Piloting a Remission Strategy in Type 2 Diabetes: Results of a Randomized Controlled Trial. J Clin Endocrinol Metab. 2017 May 1;102(5):1596-1605. doi: 10.1210/jc.2016-3373.

Study record dates

Study Major Dates

• Study Start: January 1, 2011
• Primary Completion (ACTUAL): February 1, 2015
• Study Completion (ACTUAL): September 1, 2015

Study Registration Dates

• First Submitted: August 11, 2010
• First Submitted That Met QC Criteria: August 12, 2010
• First Posted (ESTIMATE): August 13, 2010

Study Record Updates

• Last Update Posted (ACTUAL): May 21, 2020
• Last Update Submitted That Met QC Criteria: May 10, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Diabetes; Insulin; Exercise; Metformin; Diet; Lifestyle; Acarbose; Glargine
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Insulin; Insulin, Globin Zinc; Metformin; Insulin Glargine; Acarbose
• Other Study ID Numbers: REMIT Pilot; 10-346 (OTHER: Hamilton Health Sciences Research Ethics Board); Control # 139433, 143584 (OTHER: Health Canada)