Clinical trial NCT02561130: Remission Evaluation of a Metabolic Intervention in Type 2 Diabetes With Forxiga
Official title: Remission Evaluation of a Metabolic Intervention in Type 2 Diabetes With Forxiga
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Keywords: Diabetes
Insulin
Glargine
Metformin
Forxiga
Diet
Exercise
Lifestyle
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
Collaborators: name: AstraZeneca
First posted: 2015-09-25
Enrollment: 154
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 Forxiga, metformin, basal insulin glargine 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 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Achieving Drug-free Diabetes Remission in the Experimental Group Compared to the Control Group
timeFrame: 24 weeks after randomization
Secondary outcomes:
measure: Number of Participants Achieving Drug-free Diabetes Remission
timeFrame: 64 weeks after randomization
measure: Number of Participants Achieving Drug-free HbA1C < 6.0%
timeFrame: 24 weeks after randomization
measure: Number of Participants Achieving Diabetes Relapse Without Overt Hyperglycemia Off Diabetes Drugs
timeFrame: 24 weeks
measure: Glycated Hemoglobin (HbA1C)
timeFrame: 12 weeks after randomization
measure: Number of Participants With Non-severe Symptomatic Hypoglycemic Episodes
timeFrame: During 64 weeks of follow-up
measure: Percentage of Weight Loss From Baseline
timeFrame: 12 weeks after randomization
measure: Change in Waist Circumference From Baseline
timeFrame: 12 weeks after randomization
measure: Number of Participants With Severe Hypoglycemic Episodes
timeFrame: During 64 weeks of follow-up
Other outcomes:
Locations:
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Winnipeg
country: Canada
facility: Health Science Centre
state: Manitoba
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: Toronto
country: Canada
facility: LMC
state: Ontario
city: Toronto
country: Canada
facility: St. Michaels's Hospital
state: Ontario
Study officials:
affiliation: McMaster University
name: Natalia McInnes, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hamilton Health Sciences Corporation
name: Hertzel C Gerstein, MD
role: STUDY_CHAIR
References:
citation: McInnes N, Hall S, Sultan F, Aronson R, Hramiak I, Harris S, Sigal RJ, Woo V, Liu YY, Gerstein HC. Remission of Type 2 Diabetes Following a Short-term Intervention With Insulin Glargine, Metformin, and Dapagliflozin. J Clin Endocrinol Metab. 2020 Aug 1;105(8):dgaa248. doi: 10.1210/clinem/dgaa248.