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

Sponsor

Population Health Research Institute (Other)

Overall Status

Recruiting

CT.gov ID

NCT03862716

Collaborator

Novo Nordisk A/S (Industry)

160

Enrollment

Locations

Arms

51.3

Anticipated Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: IDegLira Drug: insulin degludec Drug: Metformin Behavioral: Lifestyle Therapy	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

160 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 23, 2019

Anticipated Primary Completion Date :

Jul 31, 2022

Anticipated Study Completion Date :

Jul 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention Drug: IDegLira - sc injection; Drug: metformin - oral administration; Drug: insulin degludec - sc injection; Behavioral: lifestyle therapy, diet and exercise	Drug: IDegLira Dose is titrated to achieve fasting normoglycemia Other Names: insulin degludec / liraglutide Drug: 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. Drug: 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 Other Names: diet and exercise
No Intervention: Standard Care Standard glycemic care as informed by the current clinical practice guidelines

Arm

Intervention/Treatment

Experimental: Intervention

Drug: IDegLira - sc injection; Drug: metformin - oral administration; Drug: insulin degludec - sc injection; Behavioral: lifestyle therapy, diet and exercise

Drug: IDegLira

Dose is titrated to achieve fasting normoglycemia

Other Names:

insulin degludec / liraglutide

Drug: 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.

Drug: 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

Other Names:

diet and exercise

No Intervention: Standard Care

Standard glycemic care as informed by the current clinical practice guidelines

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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 Outcome Measures

the time interval from randomization until any glucose lowering drug is restarted or relapse of hyperglycemia [Up to week 68]
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]
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 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 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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 80 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

men and women aged 30-80 years;
T2D diagnosed within 5 years
stable T2D drug regimen in the 8 weeks before randomization;
HbA1c 6.5-9.5% on no glucose lowering drugs, or 6.5%-8.0% on up to 2 glucose lowering drugs;
body mass index ≥ 23 kg/m2;
ability and willingness to perform self-monitoring of capillary blood glucose (SMBG);
willingness to wear a continuous glucose monitor on at least 3 occasions;
ability and willingness to self-inject IDegLira and insulin;
provision of informed consent.

Exclusion Criteria:

current use of insulin therapy;
history of hypoglycemia unawareness, or severe hypoglycemia requiring assistance;
history of end-stage renal disease or eGFR<45 mL/min/1.73 m2 by MDRD formula;
active liver disease or elevated alanine transferase (ALT) levels ≥ 2.5 times the upper limit of normal at the time of enrolment;
history or clinical suspicion of pancreatitis or medullary thyroid cancer;
diagnosis or first degree relative with Multiple Endocrine Neoplasia Type 2 (MEN2);
history of diabetic retinopathy requiring photocoagulation, injection therapy or vitrectomy;
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).
history of any disease requiring frequent intermittent or continuous systemic glucocorticoid treatment;
history of bariatric surgery, or planned bariatric surgery in the next 1.5 years;
history of any major illness with a life expectancy of < 3 years;
history of injury or any other condition that significantly limits participant's ability to achieve moderate levels of physical activity;
excessive alcohol intake, acute or chronic;
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;
inability to take insulin degludec, liraglutide or metformin.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Calgary	Calgary	Alberta	Canada	T2T 5C7
2	University of Alberta	Edmonton	Alberta	Canada	T6G 2E1
3	Nova Scotia Health Authority	Halifax	Nova Scotia	Canada	B3H 1V7
4	McMaster University	Hamilton	Ontario	Canada
5	St. Joseph's Hospital	London	Ontario	Canada	N6A 4V2
6	Western University	London	Ontario	Canada	N6G 2M1
7	LMC Manna Research	Oakville	Ontario	Canada	L6M 1M1
8	The Ottawa Hospital	Ottawa	Ontario	Canada	K1Y 4E9