Remission of Type 2 Diabetes With Dapagliflozin (READ Trial)

Phase 4

Completed

• Conditions: Type 2 Diabetes
• Interventions: Behavioral: Intensive lifestyle intervention; Drug: Dapagliflozin 10 MG Oral Tablet; Drug: Placebo Oral Tablet

• Registration Number: NCT04004793
• Lead Sponsor: Shanghai Zhongshan Hospital

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled study to assess the effect of dapagliflozin add-on intensive lifestyle intervention for remission of type 2 diabetes in obese patients with Type 2 Diabetes Mellitus. The study consists of a 12-months treatment period (in which they will receive either Dapagliflozin plus intensive lifestyle intervention or placebo plus intensive lifestyle intervention in addition to the background therapy), and a 2-month follow-up period after treatment period.

Detailed Description

Diabetes remission is an important issue which has not been well studied. Some studies showed that bariatric surgery and intensive lifestyle intervention could lead to remission in diabetic patients. Our present study aims to assess the effect of dapagliflozin add-on intensive lifestyle intervention on remission of type 2 diabetes in obese patients with type 2 diabetes. This is a multicenter, randomized, double-blind, placebo-controlled study. The study consists of a 12-months treatment period (in which subjects will receive either dapagliflozin plus intensive lifestyle intervention or placebo plus intensive lifestyle intervention in addition to the background therapy), and a 2-month follow-up period after treatment period.

Study Timeline

• Study First Submitted: 2019-06-28
• Study First Submitted QC: 2019-06-28
• Study First Posted: 2019-07-02
• Study Start: 2020-06-12
• Primary Completion: 2023-01-31
• Study Completion: 2023-01-31
• Status Verified: 2024-07
• Last Update Submitted: 2024-07-23
• Last Update Posted: 2024-07-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 328

Inclusion Criteria

• Men or women aged 20-70 years old who had a BMI ≥25 kg/m2.
• Subjects had been diagnosed with type 2 diabetes within 6 years
• HbA1C ≥6.5% and ≤10.0% at screening if on treatment with metformin alone or without antidiabetic agents, or HbA1C <6.5% at screening if on metformin treatment alone
• Able and willing to provide written informed consent and to comply with the study

Exclusion Criteria

1. Patients have a history of myocardial infarction, unstable angina, cardiac surgery or revascularization (coronary artery bypass graft/percutaneous transluminal coronary angioplasty), or congestive heart failure New York Heart Association Class III or IV.
2. Current insulin use.
3. Weight loss of more than 5kg within the past 6 months.
4. Women who are pregnant or plan to become pregnant.
5. Diagnosis or history of acute metabolic diabetic complications such as ketoacidosis or hyperglycemic hyperosmolar state, or diabetes insipidus within 30 days.
6. Alcohol or drug abuse within the 3 months prior to informed consent that would interfere with trial participation or any ongoing condition leading to a decreased compliance to study procedures or study drug intake.
7. Intake of an investigational drug in another trial within 30 days prior to intake of study medication in this trial or participating in another trial (involving an investigational drug and /or follow-up).
8. Patients with clinically apparent hepatobiliary disease, including but not limited to chronic active hepatitis and/or severe hepatic insufficiency. ALT or AST > 3x upper limit of normal (ULN), or serum total bilirubin (TB) >34.2 μmol/L (>2 mg/dL).
9. Patients with severe renal impairment or end-stage renal disease (eGFR< 45 mL/min/1.73 m2).
10. Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption.
11. Malignancy within 5 years of the enrollment visit.
12. Known immunocompromised status, including but not limited to, individuals who had undergone organ transplantation or acquired immunodeficiency syndrome (AIDS).
13. History of bone fracture secondary to diagnosed severe osteoporosis.
14. Current treatment with systemic steroids at time of informed consent or change in dosage of thyroid hormones within 6 weeks prior to informed consent or any other uncontrolled endocrine disorder except T2DM.
15. Administration of sibutramine, phentermine, orlistat, rimonabant, benzphetamine, diethylpropion, methamphetamine, or phendimetrazine within 30 days of enrollment visit.
16. Blood dyscrasias or any disorders causing haemolysis or unstable Red Blood Cell (e.g. malaria, babesiosis, haemolytic anaemia).
17. Administration of any other investigational drug within 30 days of planned enrollment to this study, or within 5 half-life periods of other investigational drugs.
18. Subject is, in the judgment of the Investigator, unlikely to comply with the protocol or has any severe concurrent medical or psychological condition that may affect the interpretation of efficacy or safety data

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Dapagliflozin plus intensive lifestyle intervention	Dapagliflozin 10 MG Oral Tablet	The treatment of Dapagliflozin (Forxiga®) will be initiated and maintained at 10mg every morning until the completion of the study.
Dapagliflozin plus intensive lifestyle intervention	Intensive lifestyle intervention	The treatment of Dapagliflozin (Forxiga®) will be initiated and maintained at 10mg every morning until the completion of the study.
Placebo plus intensive lifestyle intervention	Placebo Oral Tablet	The treatment of placebo will be initiated and maintained at 10mg every morning until the completion of the study.
Placebo plus intensive lifestyle intervention	Intensive lifestyle intervention	The treatment of placebo will be initiated and maintained at 10mg every morning until the completion of the study.

Primary Outcome Measures

Name	Time	Method
Incidence of patients with diabetes remission	During the 12-month intervention	Diabetes remission is defined as a HbA1c\<6.5% and a fasting glucose level of \<7.0 mmol/l in the absence of all antidiabetic medication for at least 2 months

Secondary Outcome Measures

Name	Time	Method
Net change in body fat	during both 12 and 14 months
Proportion of patients with diabetes remission	during the 12-month intervention
Net change in body weight	during both 12 and 14 months
Net change in waist circumference	during both 12 and 14 months
Net change in Serum Creatine	during both 12 and 14 months
Net change in HbA1c	during both 12 and 14 months
Net change in SBP	during both 12 and 14 months
Net change in Albuminuria	during both 12 and 14 months
Net change in HOMA-IR	during both 12 and 14 months
Net change in serum lipids	during both 12 and 14 months

Trial Locations

Locations (1)

Shanghai Medical college of; 🇨🇳 Shanghai, China