Effects of Ileo-Colonic Delivery of Conjugated Bile Acids on Glucose Metabolism, GLP-1, and Body Weight in Patients with Obesity and Type 2 Diabetes Mellitus—A Randomized Controlled Trial

Bile acid secretion increases significantly after Roux-in-Y gastric bypass and may play a role in weight loss after bariatric surgery. The acute intrajejunal-delivery or intra-rectal delivery of bile acids improves glucose metabolism. We aimed to study the effect of conjugated bile acids released on the ileo-colonic region (IC-CBAS) on glucose metabolism and body weight. In a placebo-controlled, double-blinded, randomized, 28-days trial, we studied the effect of IC-CBAS 500 mg BID on glucose metabolism, incretin hormones (GLP-1 and FGF-19), gastric emptying (scintigraphy) and weight loss in obese type 2 diabetic subjects (n=24 white patients, age=57±2 years, BMI=38.6±1.3 kg/m 2 , HbA1c=8.5±0.2%, fasting glucose 9.9±0.4 mmol/L). Participants were taking stable doses of DPP-4 inhibitors and metformin and were instructed to continue their current diet and exercise routine. Subjects underwent a meal challenge at baseline and at the end of the treatment period. The primary analyses compared treatment groups at the end of 28 days’ treatment using analysis of covariance models incorporating the corresponding baseline study value as a covariate. IC-CBAS significantly increases postprandial GLP-1 (mean p=0.04, AAB p=0.04), postprandial insulin (AAB p=0.04) and postprandial c-peptide (AAB p=0.01); and decreases fasting insulin (p=0.04) when compared to placebo. IC-CBAS also induced a numerically (but not statistically significantly) improvement in fasting glucose (delta -16 mg/dl), postprandial glucose (delta mean -14 mg/dl) and weight (delta -0.45±.4 kg) compared to placebo. There were no reported side effects, or dropouts; and no difference in FGF-19, gastric emptying or number of bowel movements. IC-CBAS 28-day treatment results in significant increase in GLP-1 and postprandial insulin, suggesting a beneficial role in incretins, insulin and glucose homeostasis. Disclosure G. Calderon Manrique: None. J. Davis: None. A.N. Bonis: None. D. Khemani: None. B. Gedulin: None. A. Vella: Research Support; Self; Novo Nordisk Inc., XOMA Corporation. Advisory Panel; Self; VTV Therapeutics, Bayer AG. M. Camilleri: None. A. Acosta: None.