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

Phase 3

Completed

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: insulin glargine; Drug: sitagliptin/metformin; Behavioral: lifestyle therapy

• Registration Number: NCT02623998
• Lead Sponsor: Population Health Research Institute

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

Study Timeline

• Study First Submitted: 2015-12-04
• Study First Submitted QC: 2015-12-04
• Study First Posted: 2015-12-08
• Study Start: 2016-07-09
• Primary Completion: 2018-09-01
• Study Completion: 2019-11-30
• Results First Submitted: 2021-12-28
• Results First Submitted QC: 2021-12-28
• Status Verified: 2022-03
• Results First Posted: 2022-03-14
• Last Update Submitted: 2022-03-15
• Last Update Posted: 2022-03-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 102

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	sitagliptin/metformin	Drug: insulin glargine - sc injection Drug: sitagliptin/metformin - oral administration Behavioral: lifestyle therapy
Intervention	lifestyle therapy	Drug: insulin glargine - sc injection Drug: sitagliptin/metformin - oral administration Behavioral: lifestyle therapy
Intervention	insulin glargine	Drug: insulin glargine - sc injection Drug: sitagliptin/metformin - oral administration Behavioral: lifestyle therapy

Primary Outcome Measures

Name	Time	Method
Number of Participants With Severe Hypoglycemic Episodes	64 weeks of follow-up
Number of Participants With Hyperglycemia Relapse in the Experimental Group Compared to the Control Group	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 Outcome Measures

Name	Time	Method
Number of Participants Achieving Drug-free Diabetes Remission	24 weeks after randomization	Diabetes remission is defined as absence of hyperglycemia relapse
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	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

Trial Locations

Locations (6)

University of Calgary; 🇨🇦 Calgary, Alberta, Canada

LMC; 🇨🇦 Markham, Ontario, Canada

Univeristy of Montreal; 🇨🇦 Montreal, Quebec, Canada

Health Science Centre; 🇨🇦 Winnipeg, Manitoba, Canada

McMaster University; 🇨🇦 Hamilton, Ontario, Canada

St. Joseph's Hospital; 🇨🇦 London, Ontario, Canada