Clinical trial NCT02623998: Remission Evaluation of a Metabolic Intervention in Type 2 Diabetes With Sitagliptin (REMIT-Sita)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: Diabetes
Insulin
Glargine
Metformin
Sitagliptin
Diet
Excercise
Lifestyle
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2015-12-08
Enrollment: 102
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Hyperglycemia Relapse in the Experimental Group Compared to the Control Group
timeFrame: 64 weeks of follow-up
measure: Number of Participants With Severe Hypoglycemic Episodes
timeFrame: 64 weeks of follow-up
Secondary outcomes:
measure: Number of Participants Achieving Drug-free Diabetes Remission
timeFrame: 24 weeks after randomization
measure: Number of Participants With Drug-free Normal Glucose Tolerance
timeFrame: 24 weeks after randomization
measure: Percent Change in Weight
timeFrame: Baseline and 12 weeks after randomization
measure: Change in Waist Circumference
timeFrame: Baseline and 12 weeks after randomization
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Winnipeg
country: Canada
facility: Health Science Centre
state: Manitoba
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: London
country: Canada
facility: St. Joseph's Hospital
state: Ontario
city: Markham
country: Canada
facility: LMC
state: Ontario
city: Montreal
country: Canada
facility: Univeristy of Montreal
state: Quebec
Study officials:
affiliation: McMaster University
name: Natalia McInnes, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hamilton Health Sciences Corporation
name: Hertzel C Gerstein, MD
role: STUDY_CHAIR
References:
citation: 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.