After Metabolic Surgery, Canagliflozin Reduces BMI and Blood Glucose Levels in Patients with Type 2 Diabetes

Canagliflozin is useful in reducing body mass index and blood glucose levels after metabolic surgery in patients with type 2 diabetes (T2D), a recent clinical trial finds. These changes may result in decreases in cardiovascular disease risk. The trial results were presented at the 2019 Annual Meeting of the American Association of Clinical Endocrinologists in Los Angeles.

“Prior to this study, it had been suggested that canagliflozin might be prescribed concurrently with metabolic surgery, but there wasn’t a lot of evidence to support the recommendation,” says Sangeeta Kashyap, MD, a physician in the Cleveland Clinic Endocrinology & Metabolism Institute and senior author of the abstract.

Patients with T2D may relapse years after successful weight loss from metabolic surgery

Metabolic surgery is gaining popularity in the treatment of obesity and T2D, as it has profoundly positive effects on weight loss and blood glucose control. Although metabolic surgery often helps patients achieve remission from T2D, glycemic control begins to degrade two years after surgery for some patients. This relapse may parallel weight regain.

This double-blind, prospective study sought to determine the effects of canagliflozin, a renal sodium glucose-cotransporter-2 inhibitor (SGLT2) on weight loss and blood glucose levels two or more years after metabolic surgery. In order to be eligible for the study, participants were required to be at least one year—but not more than 15 years—out from their metabolic surgery (i.e., either adjustable gastric banding, Roux-en-Y gastric bypass, or sleeve gastrectomy) at screening. Participants also needed to be 20-75 years of age, with a diagnosis of T2D before and after weight loss surgery, have an HbA1C of >6.5% but <11%, and an eGFR of >60mL/min.

After screening and an eight-week possible wash-out period for any other antidiabetic medications, participants (N = 16) were randomized into either canagliflozin (N = 11) or placebo groups (N = 5). There were six visits associated with the trial (at screening, baseline, randomization, six weeks, three months and six months). Following randomization, subjects in the canagliflozin group received 100 mg/day for two weeks, and then were titrated to 300 mg/day as tolerated.

Canagliflozin reduces body fat while maintaining lean mass

Participants in the canagliflozin group experienced significant reductions in BMI, body fat composition and fasting glucose levels. On average in this population, BMI decreased 2.89 kg/m2, android fat decreased 3% and truncal fat decreased 2.67%. On average, fasting blood glucose decreased 32.90 mg/dL in the canagliflozin group and increased 11.71 mg/dL in the placebo group.

“Our findings indicate that patients can expect an average weight loss of 3.5 kg on canagliflozin, while maintaining lean mass,” notes Dr. Kashyap. “In fact, the weight loss achieved in only six months of canagliflozin is comparable to two years on liraglutide. Additionally, a reduction in visceral adiposity is associated with insulin resistance and lowers the risk of cardiovascular disease.”

Initial studies found reductions in bone mineral density (BMD) in patients taking canagliflozin; however, more recent studies find no increase in fracture risk compared to glucagon-like peptide-1 (GLP-1) receptor agonists. In this trial, minimal changes in BMD were noted, though the small sample size and short duration of the study may have impacted those results.

“For patients who are seeing their weight loss plateau following metabolic surgery and who have inadequately controlled glycemic levels, canagliflozin may support further weight loss and a subsequent reduction in risk factors for cardiovascular disease,” Dr. Kashyap states.

Future research might focus on identifying a larger cohort of eligible subjects, as well as comparing the impact of other antidiabetic medications —in addition to the placebo—on weight loss and glycemic control.