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

Type 2 Diabetes Mellitus Clinical Trial

— REMITiDegLira  

Official title:

Remission Evaluation of a Metabolic Intervention for Type 2 Diabetes With IDegLira (REMIT IDegLira): A Randomized Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03862716
• Other study ID #: REMITiDegLira
• Status: Completed
• Phase: Phase 3
• Start date: April 23, 2019
• Est. completion date: July 31, 2023

Study information

• Verified date: October 2023
• Source: Population Health Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 159
• Est. completion date: July 31, 2023
• Est. primary completion date: June 15, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

Intervention

Drug:
• IDegLira
Dose is titrated to achieve fasting normoglycemia
• insulin degludec
In those who need additional insulin or who cannot tolerate IDegLira, insulin degludec will be used. Dose is titrated to achieve fasting normoglycemia.
• Metformin
Dose is titrated to 2000 mg per day or maximal tolerated dose

Behavioral:
• Lifestyle 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

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	Nova Scotia Health Authority	Halifax	Nova Scotia
Canada	McMaster University	Hamilton	Ontario
Canada	St. Joseph's Hospital	London	Ontario
Canada	Western University	London	Ontario
Canada	LMC Manna Research	Oakville	Ontario
Canada	The Ottawa Hospital	Ottawa	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Population Health Research Institute	Novo Nordisk A/S

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	the time interval from randomization until any glucose lowering drug is restarted or relapse of hyperglycemia		Up to week 68
Other	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
Other	the change in HbA1c		16, 28, 40, 52 and 68 week visit as well as the overall change
Other	the change in weight		16, 28, 40, 52 and 68 week visit as well as the overall change
Other	the change in waist circumference		16, 28, 40, 52 and 68 week visit as well as the overall change
Other	the change in hip circumference		16, 28, 40, 52 and 68 week visit as well as the overall change
Other	the change in body mass index		16, 28, 40, 52 and 68 week visit as well as the overall change
Other	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
Other	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
Other	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
Primary	Proportion of participants achieving drug-free diabetes remission	Drug-free diabetes remission is defined as HbA1C < 6.5 % off glucose-lowering agents for at least 12 weeks.	28 weeks after randomization
Secondary	Proportion of participants achieving drug-free diabetes remission		28 weeks, 40 weeks, 52 weeks and 68 weeks after randomization
Secondary	Proportion of participants achieving drug-free normoglycemia	defined as HbA1C < 6.0% off glucose-lowering agents for at least 12 weeks.	28 weeks, 40 weeks, 52 weeks and 68 weeks after randomization
Secondary	Proportion of participants achieving drug-free diabetes regression	defined as HbA1C <7.0% off glucose-lowering agents for at least 12 weeks.	28 weeks, 40 weeks, 52 weeks and 68 weeks after randomization