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

Phase 3
Completed
Conditions
Type 2 Diabetes Mellitus
Interventions
Registration Number
NCT03130426
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 iGlarLixi, 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 12-week course of treatment with iGlarLixi, metformin and lifestyle therapy, and (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 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
161
Inclusion Criteria
  1. men and women aged 30-80 years;
  2. type 2 diabetes mellitus within 5 years of diagnosis;
  3. stable diabetes drug regimen in the 10 weeks before randomization;
  4. HbA1c 6.5-9.5% on no glucose lowering drugs, or </= 8.5% on 1 glucose-lowering drug, or </= 8.0% on 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. ability and willingness to self-inject iglarlixi; and
  8. 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 renal dysfunction as evidenced by eGFR<45 mL/min/1.73 m2 by MDRD formula;
  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 enrolment;
  6. history or clinical suspicion of pancreatitis or medullary thyroid cancer, or a calcitonin level >/= 20 pg/ml;
  7. 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).
  8. history of any disease requiring frequent intermittent or continuous systemic glucocorticoid treatment;
  9. history of bariatric surgery, or planned bariatric surgery in the next 1.5 years;
  10. history of any major illness with a life expectancy of < 3 years;
  11. history of injury or any other condition that significantly limits participant's ability to achieve moderate levels of physical activity;
  12. excessive alcohol intake, acute or chronic;
  13. 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;
  14. inability to take glargine, lixisenatide or metformin

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
InterventioniGlarLixiDrug: iGlarLixi - sc injection; Drug: metformin - oral administration; Drug: insulin glargine - sc injection; Behavioral: lifestyle therapy, diet and exercise
InterventionLifestyle therapyDrug: iGlarLixi - sc injection; Drug: metformin - oral administration; Drug: insulin glargine - sc injection; Behavioral: lifestyle therapy, diet and exercise
InterventionMetforminDrug: iGlarLixi - sc injection; Drug: metformin - oral administration; Drug: insulin glargine - sc injection; Behavioral: lifestyle therapy, diet and exercise
InterventionInsulin GlargineDrug: iGlarLixi - sc injection; Drug: metformin - oral administration; Drug: insulin glargine - sc injection; Behavioral: lifestyle therapy, diet and exercise
Primary Outcome Measures
NameTimeMethod
The first occurrence of diabetes relapse64 weeks of follow-up
Secondary Outcome Measures
NameTimeMethod
Number of participants achieving drug-free diabetes remission24 weeks after randomization

Diabetes remission is defined as HbA1C \< 6.5% off diabetes drugs for at least 12 weeks

Number of participants achieving drug-free normoglycemia defined as HbA1C < 6.0% off diabetes drugs for at least 12 weeks24 weeks after randomization
Percentage of weight loss from baseline12 weeks

(Weight at randomization - weight at 12 weeks)/(weight at randomization)

Change in waist circumference from baseline12 weeks

(Waist circumference at 12 weeks - weight circumference at randomization)

Glycated hemoglobin (HbA1C)12 weeks

Expressed in Diabetes Control and Complications Trial (DCCT) units

Trial Locations

Locations (8)

McMaster University

🇨🇦

Hamilton, Ontario, Canada

The Ottawa Hospital

🇨🇦

Ottawa, Ontario, Canada

University of Calgary

🇨🇦

Calgary, Alberta, Canada

LMC

🇨🇦

Burlington, Ontario, Canada

Joanne Liutkus

🇨🇦

Cambridge, Ontario, Canada

McGill University

🇨🇦

Montreal, Quebec, Canada

Western University

🇨🇦

London, Ontario, Canada

St. Joseph's Hospital

🇨🇦

London, Ontario, Canada

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