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

Type 2 Diabetes Mellitus Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02623998
• Other study ID #: REMIT-Sita
• Status: Completed
• Phase: Phase 3
• Start date: July 9, 2016
• Est. completion date: November 30, 2019

Study information

• Verified date: March 2022
• Source: Population Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: November 30, 2019
• Est. primary completion date: September 1, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• insulin glargine
Dose is titrated to achieve fasting normoglycemia
• sitagliptin/metformin
Dose is titrated to 50/1000 mg bid or maximal tolerated dose

Behavioral:
• lifestyle therapy
Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	McMaster University	Hamilton	Ontario
Canada	St. Joseph's Hospital	London	Ontario
Canada	LMC	Markham	Ontario
Canada	Univeristy of Montreal	Montreal	Quebec
Canada	Health Science Centre	Winnipeg	Manitoba

Sponsors (2)

Lead Sponsor	Collaborator
Population Health Research Institute	Merck Sharp & Dohme Corp.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Number of Participants With Severe Hypoglycemic Episodes		64 weeks of follow-up
Secondary	Number of Participants Achieving Drug-free Diabetes Remission	Diabetes remission is defined as absence of hyperglycemia relapse	24 weeks after randomization
Secondary	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
Secondary	Percent Change in Weight		Baseline and 12 weeks after randomization
Secondary	Change in Waist Circumference		Baseline and 12 weeks after randomization