Clinical trial NCT03130426: Remission Evaluation of a Metabolic Intervention for Type 2 Diabetes With IGlarLixi
Official title: Remission Evaluation of a Metabolic Intervention for Type 2 Diabetes With IGlarLixi
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Keywords: Diabetes
iGlarLixi
Metformin
Insulin
Diet
Exercise
Lifestyle
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
Collaborators: name: Sanofi
First posted: 2017-04-26
Enrollment: 161
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 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.

Eligibility criteria: 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

Primary outcomes:
measure: The first occurrence of diabetes relapse
timeFrame: 64 weeks of follow-up
Secondary outcomes:
measure: Number of participants achieving drug-free diabetes remission
timeFrame: 24 weeks after randomization
measure: Number of participants achieving drug-free normoglycemia defined as HbA1C < 6.0% off diabetes drugs for at least 12 weeks
timeFrame: 24 weeks after randomization
measure: Percentage of weight loss from baseline
timeFrame: 12 weeks
measure: Change in waist circumference from baseline
timeFrame: 12 weeks
measure: Glycated hemoglobin (HbA1C)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Burlington
country: Canada
facility: LMC
state: Ontario
city: Cambridge
country: Canada
facility: Joanne Liutkus
state: Ontario
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: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University
state: Quebec
Study officials:
affiliation: McMaster University
name: Natalia McInnes, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: McMaster University
name: Hertzel Gerstein, MD
role: PRINCIPAL_INVESTIGATOR
References: