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Remission Evaluation of a Metabolic Intervention for Type 2 Diabetes With IDegLira

Phase 3
Completed
Conditions
Type 2 Diabetes Mellitus
Interventions
Registration Number
NCT03862716
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 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
159
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
InterventionLifestyle TherapyDrug: IDegLira - sc injection; Drug: metformin - oral administration; Drug: insulin degludec - sc injection; Behavioral: lifestyle therapy, diet and exercise
InterventionIDegLiraDrug: IDegLira - sc injection; Drug: metformin - oral administration; Drug: insulin degludec - sc injection; Behavioral: lifestyle therapy, diet and exercise
InterventionMetforminDrug: IDegLira - sc injection; Drug: metformin - oral administration; Drug: insulin degludec - sc injection; Behavioral: lifestyle therapy, diet and exercise
Interventioninsulin degludecDrug: IDegLira - sc injection; Drug: metformin - oral administration; Drug: insulin degludec - sc injection; Behavioral: lifestyle therapy, diet and exercise
Primary Outcome Measures
NameTimeMethod
Proportion of participants achieving drug-free diabetes remission28 weeks after randomization

Drug-free diabetes remission is defined as HbA1C \< 6.5 % off glucose-lowering agents for at least 12 weeks.

Secondary Outcome Measures
NameTimeMethod
Proportion of participants achieving drug-free diabetes remission28 weeks, 40 weeks, 52 weeks and 68 weeks after randomization
Proportion of participants achieving drug-free normoglycemia28 weeks, 40 weeks, 52 weeks and 68 weeks after randomization

defined as HbA1C \< 6.0% off glucose-lowering agents for at least 12 weeks.

Proportion of participants achieving drug-free diabetes regression28 weeks, 40 weeks, 52 weeks and 68 weeks after randomization

defined as HbA1C \<7.0% off glucose-lowering agents for at least 12 weeks.

Trial Locations

Locations (8)

University of Alberta

🇨🇦

Edmonton, Alberta, Canada

McMaster University

🇨🇦

Hamilton, Ontario, Canada

Western University

🇨🇦

London, Ontario, Canada

University of Calgary

🇨🇦

Calgary, Alberta, Canada

St. Joseph's Hospital

🇨🇦

London, Ontario, Canada

Nova Scotia Health Authority

🇨🇦

Halifax, Nova Scotia, Canada

LMC Manna Research

🇨🇦

Oakville, Ontario, Canada

The Ottawa Hospital

🇨🇦

Ottawa, Ontario, Canada

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