Effects of short-acting exenatide added three times daily to insulin therapy on bone metabolism in type 1 diabetes

AIMS: Glucagon-like peptide 1 (GLP-1) receptor agonists induce body weight loss, and body weight loss may reduce bone mineral density. An antiresorptive potential of long-acting GLP-1 receptor agonists has been observed in both type 1 and type 2 diabetes, but the effects of short-acting GLP-1 receptor agonism on bone metabolism have never been investigated in type 1 diabetes. The MAG1C trial evaluated the efficacy of short-acting exenatide added to insulin therapy in type 1 diabetes on bone mineral density and bone turnover markers as prespecified, secondary endpoints.MATERIALS AND METHODS: In a randomized, double-blinded, parallel-group trial, 108 individuals with type 1 diabetes aged ≥18 years on basal-bolus therapy with HbA1c 59-88 mmol/mol (7.5-10.0%) and body mass index >22.0 kg/m2 were randomized (1:1) to preprandial subcutaneous injection of 10 μg exenatide (Byetta®) before breakfast, lunch and dinner over 26 weeks as add-on treatment to regular insulin therapy.RESULTS: Exenatide elicited a 4.4 kg body weight reduction compared with placebo, but no between-group differences in bone mineral density as assessed by whole-body, hip, lumbar and forearm dual-energy X-ray absorptiometry following 26 weeks' treatment were observed. Fasting plasma levels of C-terminal telopeptides of type I collagen, a marker of bone resorption, and amino-terminal propeptide of type I procollagen, a marker of bone formation, were unchanged by exenatide compared with placebo after 26 weeks.CONCLUSIONS: Despite an exenatide-induced body weight reduction, no changes in bone metabolism were observed with exenatide added to insulin therapy in type 1 diabetes after 26 weeks. This article is protected by copyright. All rights reserved.