Type 2 Diabetes Mellitus
Conditions
Keywords
Diabetes, iGlarLixi, Metformin, Insulin, Diet, Exercise, Lifestyle
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.
Interventions
DRUGiGlarLixi
Dose is titrated to achieve fasting normoglycemia
DRUGInsulin Glargine
In those who need additional insulin or who cannot tolerate iGlarLixi, insulin glargine will be used. Dose is titrated to achieve fasting normoglycemia.
DRUGMetformin
Dose is titrated to 2000 mg daily or maximal tolerated dose
BEHAVIORALLifestyle therapy
Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving
Sponsors
Sanofi
Population Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The first occurrence of diabetes relapse | 64 weeks of follow-up |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants achieving drug-free diabetes remission | 24 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 weeks | 24 weeks after randomization | — |
| Percentage of weight loss from baseline | 12 weeks | (Weight at randomization - weight at 12 weeks)/(weight at randomization) |
| Change in waist circumference from baseline | 12 weeks | (Waist circumference at 12 weeks - weight circumference at randomization) |
| Glycated hemoglobin (HbA1C) | 12 weeks | Expressed in Diabetes Control and Complications Trial (DCCT) units |
Countries
Canada
Outcome results
None listed