Remission Evaluation of a Metabolic Intervention in Type 2 Diabetes With Forxiga

Type 2 Diabetes Mellitus Clinical Trial

Official title:

Remission Evaluation of a Metabolic Intervention in Type 2 Diabetes With Forxiga

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02561130
• Other study ID #: REMIT-Dapa
• Status: Completed
• Phase: Phase 4
• Start date: December 2015
• Est. completion date: December 31, 2018

Study information

• Verified date: November 2020
• 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 Forxiga, metformin, basal insulin glargine 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 152 patients with recently-diagnosed T2DM. Participants will be randomized to 2 treatment groups: (a) a 12-week course of treatment with Forxiga, metformin, insulin glargine 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 154
• Est. completion date: December 31, 2018
• Est. primary completion date: July 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

Inclusion Criteria:

1. men and women 30-80 years of age inclusive;

2. type 2 diabetes mellitus diagnosed by a physician within 8 years prior to patient enrollment;

3. anti-diabetic drug regimen (either drug or dose of drug) unchanged during 8 weeks prior to screening and randomization;

4. HbA1C 6.5-9.5% inclusive on no hypoglycemic agents or HbA1C = 8.0% on up to 2 glucose-lowering agents;

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 insulin;

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<60 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 enrollment;

6. history of bladder cancer or undiagnosed hematuria;

7. history of breast cancer;

8. history of polycythemia;

9. evidence of volume depletion or hypotension (systolic blood pressure < 90 mmHg);

10. systolic blood pressure > 180 mmHg or diastolic blood pressure > 105 mmHg;

11. diagnosed cardiovascular disease (unless cleared for a moderate intensity exercise program by a specialist) including:

1. any history of acute coronary syndrome, hospitalization for unstable angina, myocardial infarction, or revascularization with coronary artery bypass grafting or percutaneous coronary intervention;

2. other evidence of coronary artery disease;

3. peripheral vascular disease, valvular heart disease, cardiomyopathy, aortic dissection, tachyarrhythmias, bradyarrhythmias, prior stroke or TIA;

4. prior hospitalization for heart failure; or

5. 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).

12. dependence on oxygen;

13. history of any disease requiring frequent intermittent or continuous systemic glucocorticoid treatment;

14. history of bariatric surgery, or planned bariatric surgery in the next 1.5 years;

15. history of any major illness with a life expectancy of < 3 years;

16. history of injury or any other condition that significantly limits participant's ability to achieve moderate levels of physical activity;

17. any history of excessive alcohol intake, acute or chronic;

18. 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; reliable methods of birth control include oral contraceptive (birth control pill), hormonal injection, implant, patch, or vaginal ring, intrauterine device, barrier method (condom and spermicide), tubal ligation, partner vasectomy or abstinence;

19. known hypersensitivity to metformin, Forxiga, or insulin glargine.

Related Conditions & MeSH terms

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

Intervention

Drug:
• insulin glargine
Dose is titrated to achieve fasting normoglycemia
• metformin
Dose is titrated to 1 g bid or maximal tolerated dose
• Forxiga
Dose is titrated to 10 mg po daily or maximal tolerated dose

Behavioral:
• Lifestyle therapy
Lifestyle intervention includes individualized dietary and exercise advice and frequent visits for goal reinforcement, behavior modification and problem-solving

Locations

Country	Name	City	State
Canada	University of Calgary	Calgary	Alberta
Canada	McMaster University	Hamilton	Ontario
Canada	St. Joseph's Hospital	London	Ontario
Canada	Western University	London	Ontario
Canada	LMC	Toronto	Ontario
Canada	St. Michaels's Hospital	Toronto	Ontario
Canada	Health Science Centre	Winnipeg	Manitoba

Sponsors (2)

Lead Sponsor	Collaborator
Population Health Research Institute	AstraZeneca

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Achieving Drug-free Diabetes Remission in the Experimental Group Compared to the Control Group	Drug-free diabetes remission is defined as HbA1C < 6.5 % off glucose-lowering agents for at least 12 weeks.	24 weeks after randomization
Secondary	Number 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.	64 weeks after randomization
Secondary	Number of Participants Achieving Drug-free HbA1C < 6.0%	Drug-free complete diabetes remission is defined as HbA1C < 6.0 % off glucose-lowering agents for at least 12 weeks.	24 weeks after randomization
Secondary	Number of Participants Achieving Diabetes Relapse Without Overt Hyperglycemia Off Diabetes Drugs	Diabetes relapse without overt hyperglycemia is defined as HbA1C 6.5-6.9% off glucose-lowering agents for at least 12 weeks.	24 weeks
Secondary	Glycated Hemoglobin (HbA1C)	Expressed in Diabetes Control and Complications Trial (DCCT) units	12 weeks after randomization
Secondary	Number of Participants With Non-severe Symptomatic Hypoglycemic Episodes	Symptomatic hypoglycemic episode is defined as an event with clinical symptoms consistent with hypoglycemia.	During 64 weeks of follow-up
Secondary	Percentage of Weight Loss From Baseline	(Weight at randomization - weight at 12 weeks)/(weight at randomization)	12 weeks after randomization
Secondary	Change in Waist Circumference From Baseline	(Waist circumference at 12 weeks - waist circumference at randomization)	12 weeks after randomization
Secondary	Number of Participants With Severe Hypoglycemic Episodes	Severe hypoglycemic episode is defined as an event with clinical symptoms consistent with hypoglycemia in which the participant required the assistance of another person, and one of the following: (i) the event was associated with a documented self-measured or laboratory plasma glucose level	During 64 weeks of follow-up