Effects of canagliflozin on body weight and body composition in patients with type 2 diabetes over 104 weeks

ABSTRACT

Objectives: Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, has been associated with weight loss in a broad range of patients with type 2 diabetes mellitus (T2DM). This analysis further evaluated changes in body weight and composition with canagliflozin in two 104-week, Phase 3 studies.

Methods: In Study 1, patients aged 18–80 years (N = 1,450) received canagliflozin 100 or 300 mg or glimepiride as add-on to metformin for a 52-week core treatment period, followed by a 52-week extension period. In Study 2, patients aged 55–80 years (N = 714) received canagliflozin 100 or 300 mg or placebo added to stable background antihyperglycemic agents for a 26-week core treatment period, followed by a 78-week extension period. Percent change from baseline in body weight; proportion of patients with any weight loss, ≥5% weight loss, and ≥10% weight loss; change in body mass index (BMI) and waist circumference; change in body weight across weight-loss quartiles; and changes in body composition were evaluated in both studies.

Results: Canagliflozin 100 and 300 mg provided sustained weight loss versus either glimepiride or placebo over 104 weeks. More patients experienced any weight loss and ≥5% weight loss with canagliflozin versus comparator. Across the 3 highest weight-loss quartiles, canagliflozin provided greater weight loss versus glimepiride or placebo. BMI and waist circumference reductions were observed with canagliflozin 100 and 300 mg versus either glimepiride or placebo over 104 weeks; more patients had BMI or waist circumference reductions with canagliflozin versus comparator. Body composition analysis indicated that the majority of weight loss was due to loss of fat mass. Canagliflozin was generally well tolerated, with increased incidence of adverse events related to the SGLT2 inhibition mechanism.

Conclusions: Canagliflozin 100 and 300 mg provided sustained reductions in body weight, BMI, and waist circumference in a greater proportion of patients with T2DM versus glimepiride or placebo over 104 weeks.

Trial registration: ClinicalTrials.gov NCT00968812, NCT01106651

KEYWORDS:

• Body composition
• body weight
• canagliflozin
• sodium glucose co-transporter 2 (SGLT2) inhibitor
• type 2 diabetes mellitus
• weight loss

Acknowledgments

The authors thank all investigators, study teams, and patients for participating in these studies. The authors acknowledge Cindy Tong, MS, of Janssen Research & Development, LLC for her contribution to the data analyses.

Financial and competing interests disclosure

The studies described in this manuscript were sponsored by Janssen Research & Development, LLC. The Sponsor was involved in the design of the study; the collection, analysis, and interpretation of the data; the writing of the manuscript; and the decision to submit the manuscript for publication. All authors had full access to study data; were responsible for the integrity of the data and the accuracy of the data analysis; and reviewed, edited, and approved the report for publication. Medical writing support was provided by Alaina Mitsch, PhD, of MedErgy, and was funded by Janssen Global Services, LLC. Canagliflozin has been developed by Janssen Research & Development, LLC, in collaboration with Mitsubishi Tanabe Pharma Corporation. L Blonde has served as an investigator for AstraZeneca, Janssen Pharmaceuticals, Lexicon Pharmaceuticals, Merck & Co., Novo Nordisk, and Sanofi; has served as a speaker for AstraZeneca, Janssen Pharmaceuticals, Merck & Co., Novo Nordisk, and Sanofi; and has served as a consultant for AstraZeneca, GlaxoSmithKline, Intarcia Therapeutics, Janssen Pharmaceuticals, Merck & Co., Novo Nordisk, and Sanofi. K Stenlöf has no proprietary interest in the tested product, does not have a significant equity interest in the sponsor of the covered study, and has not received significant payments of other sorts from the sponsor. A Fung, J Xie, W Canovatchel, and G Meininger are full-time employees of Janssen Research & Development, LLC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.