Type 2 Diabetes Mellitus
Conditions
Keywords
Diabetes, IDegLira, Metformin, Insulin, Diet, Excercise, 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 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.
Interventions
DRUGIDegLira
Dose is titrated to achieve fasting normoglycemia
DRUGinsulin degludec
In those who need additional insulin or who cannot tolerate IDegLira, insulin degludec will be used. Dose is titrated to achieve fasting normoglycemia.
DRUGMetformin
Dose is titrated to 2000 mg per day or maximal tolerated dose
BEHAVIORALLifestyle Therapy
Lifestyle intervention includes individualized dietary and exercise advice targeting at least 5% weight loss with frequent visits and coaching for goal reinforcement, behavior modification and problem-solving
Sponsors
Novo Nordisk A/S
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. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving drug-free diabetes remission | 28 weeks after randomization | Drug-free diabetes remission is defined as HbA1C \< 6.5 % off glucose-lowering agents for at least 12 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of participants achieving drug-free diabetes remission | 28 weeks, 40 weeks, 52 weeks and 68 weeks after randomization | — |
| Proportion of participants achieving drug-free normoglycemia | 28 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 regression | 28 weeks, 40 weeks, 52 weeks and 68 weeks after randomization | defined as HbA1C \<7.0% off glucose-lowering agents for at least 12 weeks. |
Other
| Measure | Time frame |
|---|---|
| the change in waist circumference | 16, 28, 40, 52 and 68 week visit as well as the overall change |
| the change in hip circumference | 16, 28, 40, 52 and 68 week visit as well as the overall change |
| the change in body mass index | 16, 28, 40, 52 and 68 week visit as well as the overall change |
| the time interval from randomization until any glucose lowering drug is restarted or relapse of hyperglycemia | Up to week 68 |
| 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 | from randomization until the 6, 16, 28 and 52 week visit |
| 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 | from randomization until the 6, 16, 28 and 52 week visit |
| 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 | from randomization until the 6, 16, 28 and 52 week visit |
| 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 | Up to week 68 |
| the change in HbA1c | 16, 28, 40, 52 and 68 week visit as well as the overall change |
| the change in weight | 16, 28, 40, 52 and 68 week visit as well as the overall change |
Countries
Canada
Outcome results
None listed