Denosumab’s Role in Reducing Type 2 Diabetes Risk and Improving Glycaemic Control in Osteoporotic Patients - A Meta-analysis
Abstract
Introduction: Osteoporosis, common among postmenopausal women and the elderly, is primarily associated with increased fracture risk. Emerging evidence suggests a potential link between bone metabolism and glucose regulation with implications for type 2 diabetes (T2D) risk. Denosumab, a monoclonal antibody effective in increasing bone density, might also reduce the risk of T2D. This meta-analysis evaluates the impact of denosumab on T2D risk and glycaemic markers, including fasting blood sugar (FBS), HbA1c, and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).
Materials and methods: A comprehensive search of PubMed, Cochrane Library, and Embase identified randomised controlled trials and cohort studies comparing denosumab with placebo or other osteoporosis treatments. Study quality was assessed using the Cochrane risk-of-bias tool. The primary outcome was T2D incidence, with risk ratios and related metrics analysed for consistency.
Results: Results revealed a 22% reduction in T2D incidence with denosumab (HR = 0.78, 95% CI 0.70, 0.87, p<0.00001, I² = 62%) with small benefit in terms of absolute risk reduction (ARR = -0.01, 95% CI -0.03, 0.01, p = 0.19). Denosumab also resulted in small reductions in FBS in the included RCTs (SMD = -0.13, 95% CI -0.30, 0.03, p = 0.0798) and non-randomised trials (SMD = -0.28, 95% CI -0.63, 0.06, p = 0.0947). There were slightly larger but still non-significant reductions in HbA1c (SMD = -0.44, p = 0.10) and HOMA-IR (SMD = -0.21, p = 0.114).
Conclusion: Denosumab may confer metabolic benefits beyond bone health, particularly in reducing T2D risk and improving FBS. While this aligns with its role in modulating bone turnover and RANKL inhibition, inconsistent outcomes for HbA1c and HOMA IR underscore the need for further investigation into its glycaemic effects.
Abstract | Reference
