Clinical trial NCT03862716: Remission Evaluation of a Metabolic Intervention for Type 2 Diabetes With IDegLira
Official title: Remission Evaluation of a Metabolic Intervention for Type 2 Diabetes With IDegLira (REMIT IDegLira): A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: Diabetes
IDegLira
Metformin
Insulin
Diet
Excercise
Lifestyle
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
First posted: 2019-03-05
Enrollment: 159
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 IDegLira, metformin, 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 160 patients with recently-diagnosed T2DM. Participants will be randomized to 2 treatment groups: (a) a 16-week course of treatment with IDegLira, metformin and lifestyle therapy, and (b) standard diabetes therapy, and followed for a total of 68 weeks (1 year and 4 months). In all participants with HbA1C\<7.3% at the 16 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 experience hyperglycemia 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 aged 30-80 years;
2. T2D diagnosed within 5 years
3. stable T2D drug regimen in the 8 weeks before randomization;
4. HbA1c 6.5-9.5% on no glucose lowering drugs, or 6.5%-8.0% on up to 2 glucose lowering drugs;
5. body mass index ≥ 23 kg/m2;
6. ability and willingness to perform self-monitoring of capillary blood glucose (SMBG);
7. willingness to wear a continuous glucose monitor on at least 3 occasions;
8. ability and willingness to self-inject IDegLira and 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. history of end-stage renal disease or eGFR\<45 mL/min/1.73 m2 by MDRD formula;
4. active liver disease or elevated alanine transferase (ALT) levels ≥ 2.5 times the upper limit of normal at the time of enrolment;
5. history or clinical suspicion of pancreatitis or medullary thyroid cancer;
6. diagnosis or first degree relative with Multiple Endocrine Neoplasia Type 2 (MEN2);
7. history of diabetic retinopathy requiring photocoagulation, injection therapy or vitrectomy;
8. history of cardiovascular disease (unless cleared for a moderate intensity exercise program by a specialist) including: i. acute coronary syndrome, hospitalization for unstable angina, myocardial infarction, or revascularization with coronary artery bypass grafting or percutaneous coronary intervention; ii. peripheral vascular disease, valvular heart disease, cardiomyopathy, aortic dissection, tachyarrhythmias, bradyarrhythmias, prior stroke or TIA; iii. prior hospitalization for heart failure; or iv. ECG findings concerning for ischemic heart disease (i.e. pathological Q-waves, ST-segment-T-wave abnormalities in contiguous leads, left anterior hemiblock, left bundle branch block, second or third degree atrioventricular block).
9. history of any disease requiring frequent intermittent or continuous systemic glucocorticoid treatment;
10. history of bariatric surgery, or planned bariatric surgery in the next 1.5 years;
11. history of any major illness with a life expectancy of \< 3 years;
12. history of injury or any other condition that significantly limits participant's ability to achieve moderate levels of physical activity;
13. excessive alcohol intake, acute or chronic;
14. currently pregnant, or breastfeeding, or not using a reliable method of birth control for the duration of the trial in all females with childbearing potential;
15. inability to take insulin degludec, liraglutide or metformin.

Primary outcomes:
measure: Proportion of participants achieving drug-free diabetes remission
timeFrame: 28 weeks after randomization
Secondary outcomes:
measure: Proportion of participants achieving drug-free diabetes remission
timeFrame: 28 weeks, 40 weeks, 52 weeks and 68 weeks after randomization
measure: Proportion of participants achieving drug-free normoglycemia
timeFrame: 28 weeks, 40 weeks, 52 weeks and 68 weeks after randomization
measure: Proportion of participants achieving drug-free diabetes regression
timeFrame: 28 weeks, 40 weeks, 52 weeks and 68 weeks after randomization
Other outcomes:
measure: the time interval from randomization until any glucose lowering drug is restarted or relapse of hyperglycemia
timeFrame: Up to week 68
measure: the time interval from the 16 week visit (i.e. when glucose lowering drugs are to be stopped) until any glucose lowering drug is restarted or relapse of hyperglycemia
timeFrame: Up to week 68
measure: the change in HbA1c
timeFrame: 16, 28, 40, 52 and 68 week visit as well as the overall change
measure: the change in weight
timeFrame: 16, 28, 40, 52 and 68 week visit as well as the overall change
measure: the change in waist circumference
timeFrame: 16, 28, 40, 52 and 68 week visit as well as the overall change
measure: the change in hip circumference
timeFrame: 16, 28, 40, 52 and 68 week visit as well as the overall change
measure: the change in body mass index
timeFrame: 16, 28, 40, 52 and 68 week visit as well as the overall change
measure: the change in coefficient of variation over 2 weeks (defined as 4-8 mmol/l), based on up to 2 weeks of Abbott Freestyle Libre ProTM sensor wear
timeFrame: from randomization until the 6, 16, 28 and 52 week visit
measure: the change in interquartile range over 2 weeks (defined as 4-8 mmol/l), based on up to 2 weeks of Abbott Freestyle Libre ProTM sensor wear
timeFrame: from randomization until the 6, 16, 28 and 52 week visit
measure: the change in time range over 2 weeks (defined as 4-8 mmol/l), based on up to 2 weeks of Abbott Freestyle Libre ProTM sensor wear
timeFrame: from randomization until the 6, 16, 28 and 52 week visit
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Halifax
country: Canada
facility: Nova Scotia Health Authority
state: Nova Scotia
city: Hamilton
country: Canada
facility: McMaster University
state: Ontario
city: London
country: Canada
facility: St. Joseph's Hospital
state: Ontario
city: London
country: Canada
facility: Western University
state: Ontario
city: Oakville
country: Canada
facility: LMC Manna Research
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
Study officials:
affiliation: McMaster University
name: Zubin Punthakee, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University
name: Hertzel Gerstein, MD
role: STUDY_CHAIR
References: