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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: insulin glargine; Drug: sitagliptin/metformin; Behavioral: lifestyle therapy

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

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2T 5C7
      • University of Calgary
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 3P4
      • Health Science Centre
  • Ontario
    • Hamilton, Ontario, Canada
      • McMaster University
    • London, Ontario, Canada, N6A 4V2
      • St. Joseph's Hospital
    • Markham, Ontario, Canada
      • LMC
  • Quebec
    • Montreal, Quebec, Canada
      • Univeristy of Montreal

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 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Principal Investigator: Natalia McInnes, MD, McMaster University; Study Chair: Hertzel C Gerstein, MD, Hamilton Health Sciences Corporation

Publications and helpful links

General Publications

• McInnes N, Hall S, Hramiak I, Sigal RJ, Goldenberg R, Gupta N, Rabasa-Lhoret R, Braga M, Woo V, Sultan F, Otto R, Smith A, Sherifali D, Liu YY, Gerstein HC; REMIT-sita Collaborative Group. Remission of Type 2 Diabetes Following a Short-term Intensive Intervention With Insulin Glargine, Sitagliptin, and Metformin: Results of an Open-label Randomized Parallel-Design Trial. Diabetes Care. 2022 Jan 1;45(1):178-185. doi: 10.2337/dc21-0278.

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2016
• Primary Completion (Actual): September 1, 2018
• Study Completion (Actual): November 30, 2019

Study Registration Dates

• First Submitted: December 4, 2015
• First Submitted That Met QC Criteria: December 4, 2015
• First Posted (Estimate): December 8, 2015

Study Record Updates

• Last Update Posted (Actual): March 25, 2022
• Last Update Submitted That Met QC Criteria: March 15, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Diabetes; Insulin; Metformin; Diet; Sitagliptin; Lifestyle; Glargine; Excercise
• 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; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Insulin Glargine; Sitagliptin Phosphate
• Other Study ID Numbers: REMIT-Sita