Abstract
Background Denosumab is a therapy for the treatment of osteoporosis, recommended by the UK National Institute for Clinical Excellence (NICE). Observational studies have previously demonstrated that denosumab decreases the risk of incident type 2 diabetes (T2D).
Aims To evaluate the impact of denosumab on the i) incidence of T2D, and ii) long-term health outcomes (micro- [neuropathy, retinopathy, nephropathy] and macrovascular [cardiovascular disease, cerebrovascular accident] complications, and all-cause mortality) in patients with T2D, before iii) combining results with prior studies using meta-analysis.
Methods A retrospective analysis of data in a large global federated database (TriNetX, Cambridge MA, USA) was conducted from 331,375 patients, without baseline T2D or cancer, prescribed either denosumab (treatment, n=45,854) or bisphosphonates (control, n=285,521), across 83 health care organisations. Propensity score matching (1:1) of confounders was undertaken which resulted in n=45,851 in each cohort. Secondary analysis further evaluated the impact of denosumab on long-term health outcomes in patients with T2D. Additionally, we systematically searched prior literature that assessed association between denosumab and T2D. Estimates were pooled using random-effects meta-analysis. Risk of bias and evidence quality was assessed using Cochrane endorsed tools.
Results Denosumab (vs. bisphosphonates) was associated with lower risk of incident T2D over 5 years (hazard ratio 0.83 (95% confidence interval 0.78-0.88)). Secondary analysis demonstrated significant risk reduction in all-cause mortality (0.79 [0.72-0.87]), and foot ulceration (0.67 [0.53-0.86]). Also, pooled results from four studies (three observational, one randomised controlled trial) following meta-analysis showed a reduced relative risk (RR (95% CI)) for incident T2D in patients prescribed denosumab (0.83 [0.79-0.87]) (I2 = 10.76%).
Conclusion This is the largest cohort study to demonstrate that denosumab treatment is associated with reduced risk of incident T2D, as well as demonstrating an associated reduced risk of all-cause mortality and microvascular complications; findings which may influence guideline development in the treatment of osteoporosis, particularly in patients at high risk of T2D.
Aims To evaluate the impact of denosumab on the i) incidence of T2D, and ii) long-term health outcomes (micro- [neuropathy, retinopathy, nephropathy] and macrovascular [cardiovascular disease, cerebrovascular accident] complications, and all-cause mortality) in patients with T2D, before iii) combining results with prior studies using meta-analysis.
Methods A retrospective analysis of data in a large global federated database (TriNetX, Cambridge MA, USA) was conducted from 331,375 patients, without baseline T2D or cancer, prescribed either denosumab (treatment, n=45,854) or bisphosphonates (control, n=285,521), across 83 health care organisations. Propensity score matching (1:1) of confounders was undertaken which resulted in n=45,851 in each cohort. Secondary analysis further evaluated the impact of denosumab on long-term health outcomes in patients with T2D. Additionally, we systematically searched prior literature that assessed association between denosumab and T2D. Estimates were pooled using random-effects meta-analysis. Risk of bias and evidence quality was assessed using Cochrane endorsed tools.
Results Denosumab (vs. bisphosphonates) was associated with lower risk of incident T2D over 5 years (hazard ratio 0.83 (95% confidence interval 0.78-0.88)). Secondary analysis demonstrated significant risk reduction in all-cause mortality (0.79 [0.72-0.87]), and foot ulceration (0.67 [0.53-0.86]). Also, pooled results from four studies (three observational, one randomised controlled trial) following meta-analysis showed a reduced relative risk (RR (95% CI)) for incident T2D in patients prescribed denosumab (0.83 [0.79-0.87]) (I2 = 10.76%).
Conclusion This is the largest cohort study to demonstrate that denosumab treatment is associated with reduced risk of incident T2D, as well as demonstrating an associated reduced risk of all-cause mortality and microvascular complications; findings which may influence guideline development in the treatment of osteoporosis, particularly in patients at high risk of T2D.
| Original language | English |
|---|---|
| Journal | Diabetes, Obesity and Metabolism |
| Early online date | 25 Jun 2024 |
| DOIs | |
| Publication status | E-pub ahead of print - 25 Jun 2024 |
