Denosumab for osteoporosis is associated with reduced diabetes risk compared to bisphosphonates

1. In a cohort of adults with osteoporosis, the use of denosumab was linked to a reduced risk of developing type 2 diabetes when compared to the use of oral bisphosphonates.

Evidence Rating Level: 2 (Good)

Antiresorptive drugs are the most prevalent treatment for osteoporosis. One such potent antiresorptive drug is denosumab, a monoclonal antibody against the receptor activator of nuclear factor κ B (RNAK) ligand (RANKL). Recent studies suggest that higher RANKL levels were correlated with an increased risk of developing type 2 diabetes (T2D), while inhibiting RANKL/RANK signaling has been associated with improved glucose homeostasis in T2D or prediabetes patients. Given that the literature surrounding the incidence of T2D among denosumab users is limited, and that approximately 80% of denosumab users had previously used other anti-osteoporosis drugs like oral bisphosphonates, this study aimed to examine the effect of switching to denosumab versus continuing oral bisphosphonate on the risk of incident T2D over a 5-year follow-up period. Using the IQVIA Medical Research Data (IMRD) UK primary care database, 4301 eligible individuals (mean age 69 years, 94% women) who switched to or initiated denosumab were matched on propensity scores to 21 038 users (mean age 72 years, 81% women) of oral bisphosphonates. Those in the denosumab cohort had a T2D incidence of 5.7 per 1000 person-years compared to 8.3 per 1000 person-years in the matched oral bisphosphonate cohort. In other words, initiation of denosumab reduced the risk of incident T2D (hazard ratio 0.68, 95% CI 0.52 to 0.89). Participants at a higher risk of T2D – those with prediabetes or obesity – seemed to benefit more from denosumab initiation compared with oral bisphosphonate use with a hazard ratio of 0.54 (95% Cl 0.35 to 0.82) and 0.65 (95% Cl 0.40 to 1.06) respectively. Overall, this study provides evidence that treating osteoporosis with denosumab may simultaneously reduce the risk of T2D, which raises important considerations when treating patients with osteoporosis.

Click to read the study in BMJ

Image: PD

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