Risk of Fracture With Dipeptidyl Peptidase-4 Inhibitors, Glucagon-like Peptide-1 Receptor Agonists, or Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Type 2 Diabetes Mellitus: A Systematic Review and Network Meta-analysis Combining 177 Randomized Controlled Trials With a Median Follow-Up of 26 weeks

Abstract

Aim: This study aims to investigate the association between the use of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), or sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and the risk of fracture among patients with type 2 diabetes mellitus.Methods: Medline, Embase, Cochrane Library, and Clinical-Trials.gov databases were searched for randomized controlled trials (RCTs). Network meta-analysis was performed for total fracture and a series of secondary outcomes.Results: A total of 177 RCTs (n = 165,081) involving the risk of fracture were identified (a median follow-up of 26 weeks). DPP-4i, GLP-1 RAs, and SGLT-2i did not increase total fracture risk compared with insulin (odds ratio: 0.86, 95% confidence interval: 0.39–1.90; 1.05, 0.54–2.04; 0.88, and 0.39–1.97, respectively), metformin (1.41, 0.48–4.19; 1.72, 0.55–5.38; 1.44, 0.48–4.30), sulfonylureas (0.77, 0.50–1.20; 0.94, 0.55–1.62; 0.79, 0.48–1.31), thiazolidinediones (0.82, 0.27–2.44; 1.00, 0.32–3.10; 0.83, 0.27–2.57), α-glucosidase inhibitor (4.92, 0.23–103.83; 5.99, 0.28–130.37; 5.01, 0.23–107.48), and placebo (1.04, 0.84–1.29; 1.27, 0.88–1.83; 1.06, 0.81–1.39).Conclusions: The use of DPP-4i, GLP-1 RAs, or SGLT-2i is unlikely to increase the risk of fracture among type 2 diabetes mellitus patients.