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

NCT02561130 | Completed Phase 4 Results

• 1 other identifier: REMIT-Dapa
• Study Type: interventional
• Target: 154
• Locations: 1 country
• Sites: 7

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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Diabetes; Insulin; Glargine; Metformin; Forxiga; Diet; Exercise; Lifestyle

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

• Number of Participants Achieving Drug-free Diabetes Remission

  64 weeks after randomization

• Number of Participants Achieving Drug-free HbA1C < 6.0%

  24 weeks after randomization

• Number of Participants Achieving Diabetes Relapse Without Overt Hyperglycemia Off Diabetes Drugs

  24 weeks

• Glycated Hemoglobin (HbA1C)

  12 weeks after randomization

• Number of Participants With Non-severe Symptomatic Hypoglycemic Episodes

  During 64 weeks of follow-up

Study Arms (2)

Intervention

EXPERIMENTAL

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

Drug: insulin glargine; Drug: metformin; Drug: Forxiga; Behavioral: Lifestyle therapy

Standard Care

NO INTERVENTION

Standard glycemic care as informed by the current clinical practice guidelines

Interventions

insulin glargine DRUG

Dose is titrated to achieve fasting normoglycemia

Also known as: Lantus

Intervention

metformin DRUG

Dose is titrated to 1 g bid or maximal tolerated dose

Intervention

Forxiga DRUG

Dose is titrated to 10 mg po daily or maximal tolerated dose

Also known as: dapagliflozin

Intervention

Lifestyle therapy BEHAVIORAL

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

Also known as: diet and exercise

Intervention

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• men and women 30-80 years of age inclusive;
• type 2 diabetes mellitus diagnosed by a physician within 8 years prior to patient enrollment;
• anti-diabetic drug regimen (either drug or dose of drug) unchanged during 8 weeks prior to screening and randomization;
• HbA1C 6.5-9.5% inclusive on no hypoglycemic agents or HbA1C ≤ 8.0% on up to 2 glucose-lowering agents;
• body mass index ≥ 23 kg/m2;
• ability and willingness to perform self-monitoring of capillary blood glucose (SMBG);
• ability and willingness to self-inject insulin;
• provision of informed consent.

You may not qualify if:

• current use of insulin therapy;
• history of hypoglycemia unawareness, or severe hypoglycemia requiring assistance;
• history of end-stage renal disease or renal dysfunction as evidenced by eGFR\<60 mL/min/1.73 m2 by MDRD formula;
• history of lactic acidosis or diabetic ketoacidosis;
• active liver disease or elevated alanine transferase (ALT) levels ≥ 2.5 times upper limit of normal at the time of enrollment;
• history of bladder cancer or undiagnosed hematuria;
• history of breast cancer;
• history of polycythemia;
• evidence of volume depletion or hypotension (systolic blood pressure \< 90 mmHg);
• systolic blood pressure \> 180 mmHg or diastolic blood pressure \> 105 mmHg;
• diagnosed cardiovascular disease (unless cleared for a moderate intensity exercise program by a specialist) including:
• any history of acute coronary syndrome, hospitalization for unstable angina, myocardial infarction, or revascularization with coronary artery bypass grafting or percutaneous coronary intervention;
• other evidence of coronary artery disease;
• peripheral vascular disease, valvular heart disease, cardiomyopathy, aortic dissection, tachyarrhythmias, bradyarrhythmias, prior stroke or TIA;
• prior hospitalization for heart failure; or

Sponsors & Collaborators

• Population Health Research Institute: lead
• AstraZeneca: collaborator

Study Sites (7)

University of Calgary

Calgary, Alberta, T2T 5C7, Canada

Location

Health Science Centre

Winnipeg, Manitoba, R3E 3P4, Canada

Location

McMaster University

Hamilton, Ontario, L8N 3Z5, Canada

Location

St. Joseph's Hospital

London, Ontario, N6A 4V2, Canada

Location

Western University

London, Ontario, N6G 2M1, Canada

Location

LMC

Toronto, Ontario, M4G 3E8, Canada

Location

St. Michaels's Hospital

Toronto, Ontario, M5C 2T2, Canada

Location

Related Publications (1)

• 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.

  PMID: 32403130 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Diabetes Mellitus; Insulin Resistance; Motor Activity

Interventions

Insulin Glargine; Metformin; dapagliflozin; Diet; Exercise

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism; Behavior

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Biguanides; Guanidines; Amidines; Organic Chemicals; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Results Point of Contact

• Title: Natalia McInnes
• Organization: McMaster University

natalia.mcinnes@mcmaster.ca

905-521-2100

Study Officials

• Natalia McInnes, MD

  McMaster University

  PRINCIPAL INVESTIGATOR

• Hertzel C Gerstein, MD

  Hamilton Health Sciences Corporation

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2015
• First Posted: September 25, 2015
• Study Start: December 1, 2015
• Primary Completion: July 1, 2017
• Study Completion: December 31, 2018
• Last Updated: November 24, 2020
• Results First Posted: November 24, 2020

Record last verified: 2020-11

Locations

CA (7)