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Canagliflozin after metabolic surgery may aid weight loss, reduce glucose levels



– Patients who took the sodium-glucose cotransporter-2 inhibitor canagliflozin after undergoing metabolic surgery experienced reductions in blood glucose, body mass index, and truncal body fat, results from a small pilot study have shown.

Dr. Sangeeta R. Kashyap of the Cleveland Clinic Doug Brunk/MDedge News

Dr. Sangeeta R. Kashyap

“We hypothesized that canagliflozin would be a good choice for these patients, because these drugs work independently of insulin,” the study’s principal investigator, Sangeeta R. Kashyap, MD, said in an interview at the annual scientific and clinical congress of the American Association of Clinical Endocrinologists. “They help promote weight loss and improve blood pressure. [After] bariatric surgery, patients have an issue with weight regain, and sometimes their diabetes comes back.”

In what she said is the first prospective, randomized, controlled trial of its kind, Dr. Kashyap, an endocrinologist at the Cleveland Clinic, and her colleagues enrolled 11 women and 5 men with type 2 diabetes who had undergone Roux-en-Y gastric bypass or sleeve gastrectomy to study the effects of canagliflozin on clinical parameters over a period of 6 months. At baseline, the patients’ mean body mass index was 39.2 kg/m2 and their mean hemoglobin A1c level was 7.4%. The researchers used maximum likelihood estimation in a linear mixed-effect model to deduce differences between the treatment and placebo groups. Patients randomized to the study drug were assigned a 6-month course of canagliflozin, starting on 100 mg for 2 weeks titrated up to 300 mg daily.

At 6 months, fasting glucose was significantly reduced in the canagliflozin group, compared with baseline (from 163 to 122 mg/dL; P = .007), but it rose in the placebo group (from 164 to 192 mg/dL), a between-group difference that fell short of statistical significance (P = .12). In addition, C-reactive protein in the treatment group fell from 8.9 mg/L to 3.9 mg/L, but rose from 1.6 mg/L to 4.7 mg/L in the placebo group, a between-group difference that trended toward significance (P = .07).

During the 6-month study period, the mean BMI fell from 39.6 kg/m2 to 38 kg/m2 in the canagliflozin group but increased from 38 to 41 in the placebo group, a between-group difference that reached statistical significance (P = .014). Mean changes in body fat (a reduction of 1.82%), truncal fat (a reduction of 2.67%), and android fat (a reduction of 3%) also reached statistical significance in the treatment group, compared with the placebo group. Reductions in adiponectin, leptin, and high–molecular weight adiponectin did not reach statistical significance.

“I think these drugs have a place in post–bariatric surgery care,” Dr. Kashyap said. “Canagliflozin after metabolic surgery improved weight-loss outcomes and blood sugar levels. It also improved abdominal fat levels, and in this way might even lower cardiovascular disease risk in these patients.”

She acknowledged the study’s small sample size and single-center design as limitations. “It was very difficult to recruit patients for this study,” she said. “Not many patients have recurrent diabetes after bariatric surgery.”

Janssen provided funding to Dr. Kashyap for the trial.

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