Canagliflozin aids additional weight loss after refractory bariatric surgery
LOS ANGELES — Adults who underwent bariatric surgery and experienced diabetes remission but later regained weight and redeveloped the disease experienced weight loss and improvements in cardiometabolic parameters after 6 months of canagliflozin therapy, according to study data presented at the AACE Annual Scientific and Clinical Congress.
“Patients with diabetes often undergo bariatric surgery and have terrific results,” Sangeeta Kashyap, MD, associate professor of medicine at Cleveland Clinic Lerner College of Medicine and staff physician in the department of endocrinology at Cleveland Clinic, told Endocrine Today. “We also know that there are people that regain weight and redevelop diabetes. The question for endocrinologists is, now what? How do you treat them? They have already undergone the biggest intervention you can give them, and they failed that.”
In a pilot, randomized, double-blind trial, Kashyap and colleagues analyzed data from 16 patients with type 2 diabetes who underwent either Roux-en-Y gastric bypass or sleeve gastrectomy at least 1 year before recruitment (11 women; mean age, 54 years; mean baseline BMI, 39.2 kg/m²; mean baseline HbA1c, 7.4%). Researchers assigned participants to daily canagliflozin (Invokana, Janssen; n = 11) or placebo (n = 5) for 6 months. Researchers used linear mixed-effect models to calculate between-group differences in body weight, BMI, body composition, C-reactive protein and blood glucose.
“We thought canagliflozin would be a good choice because it doesn’t rely on insulin,” Kashyap said. “It results in the elimination of glucose in the kidneys, so we thought it might complement the benefits patients get from metabolic surgery and may even extend those.”
At 6 months, BMI for participants in the canagliflozin group decreased from a mean of 39.6 kg/m² to 38 kg/m², whereas those in the placebo group experienced a mean 3 kg/m² BMI gain.
Patients in the canagliflozin group also experienced a mean 1.82% decrease in body fat compared with a 2.65% gain in the placebo group (between-group difference, –4.47; 95% CI, –8.82 to –0.11), as well as a mean 1.82% gain in lean mass vs. a –2.65% loss in the placebo group (between-group difference, 4.47; 95% CI, 0.11-8.82). Patients in the canagliflozin group also experienced greater decreases in truncal, android and gynoid fat percentages vs. placebo, according to researchers.
Patients assigned canagliflozin also experienced a mean 32.9 mg/dL reduction in fasting blood glucose at 6 months, in addition to a reduction in C-reactive protein (P = .066), Kashyap said.
“We did not see a difference in HbA1c, and that is because if the placebo group became hyperglycemic, we rescued them with insulin,” Kashyap said. “Fasting glucose was clearly better in the canagliflozin group; weight loss was better; body fat percentage went down; central fat, truncal fat and C-reactive protein was reduced.”
Kashyap said the findings suggest that SGLT2 inhibitors are a good choice after bariatric surgery for patients who are struggling to maintain body weight.
“Other drugs like metformin have gastrointestinal side effects, and a lot of people cannot tolerate GLP-1 receptor agonists,” Kashyap said. “Other options cause hypoglycemia and weight gain, and that is the last thing patients want after bariatric surgery.”
Kashyap said the researchers plan to conduct a larger study to confirm the findings. – by Regina Schaffer
Kashyap SR, et al. Canagliflozin facilitates favorable weight loss outcomes in post metabolic surgery patients. Presented at: AACE Annual Scientific and Clinical Congress; April 24-28, 2019; Los Angeles.
Disclosure: Kashyap reports no relevant financial disclosures.