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Karim Kheniser – Research Coordinator, Department of Endocrinology and Metabolism, Cleveland Clinic, Cleveland, Ohio.

James Bena, MS – Principal Biostatistician, Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio.

Sangeeta Kashyap, MD – Professor of Medicine, Department of Endocrinology and Metabolism, Cleveland Clinic, Cleveland, Ohio.

Philip Schauer, MD – Director, Bariatric & Metabolic Institute, Cleveland Clinic, Bariatric and Metabolic Institute, Cleveland, OH, USA.


Objective : Patients who have underwent metabolic surgery are at risk for weight regain. Limited evidence exists on the effects of sodium-glucose cotransporter-2 inhibitors on cardiometabolic parameters in patients who have underwent metabolic surgery. The aim of the trial was to elucidate the effects of canagliflozin on clinical parameters in type II diabetes (T2D) subjects who underwent metabolic surgery.

Methods : A prospective, randomized, and double-blinded trial was instituted to recruit post-metabolic surgery patients (Roux-en-Y gastric bypass or sleeve gastrectomy). Patients allocated into the control or medication group met specific inclusion criteria: diagnosed with T2D, hemoglobin A1c (HbA1c) > 6.5%, 18-75 years of age, and underwent metabolic surgery at least one year prior, but < 15 years ago. Subjects (n=16, 11 female) were enrolled in the study for six months. Baseline mean body mass index (BMI), age, and HbA1c, were 39.2 kg/m2, 54 years, and 7.4%, respectively. Using maximum likelihood estimation, a linear mixed effect model was conducted to deduce group differences. Mean changes (95% confidence intervals) in weight, BMI, body composition, and blood glucose were reported. A p-value < 0.05 was considered statistically significant.

Results : Mean changes in weight and BMI were significant between groups; furthermore, mean changes in percent body, lean, truncal, and android fat achieved statistical significance (p2 (-2.12,-0.36) in the medication group. Moreover, mean percent change in android and truncal fat were -3% (-5.67,-0.32) and -2.67% (-5.19,-0.16), respectively. Finally, fasting glucose significantly reduced by 32.90 mg/dL (-56.02,-9.79) after six months in the medication group (p<0.05). 

Discussion : Given that canagliflozin fostered weight loss in patients who underwent metabolic surgery, the implications are clinically relevant. The concurrent application of canagliflozin and metabolic surgery in patients who are obese and diagnosed with T2D can be beneficial. Specifically, their synergistic effects translate into favorable weight loss outcomes and possibly further reductions in cardiovascular risk. The addition of canagliflozin as therapy in patients who have undergone metabolic surgery can amplify weight loss outcomes acutely post-surgery and/or mitigate weight regain long-term. 

Conclusion : Canagliflozin can foster improved weight loss outcomes in patients who have underwent metabolic surgery. In turn, there may be a further reduction in cardiovascular disease risk. 

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