Denosumab, for osteoporosis, reduces the incidence of type 2 diabetes, risk of foot ulceration and all-cause mortality in adults, compared with bisphosphonates: An analysis of real-world, cohort data, with a systematic review and meta-analysis.

Henney, Alex E, Riley, David R, O'Connor, Ben, Hydes, Theresa J, Anson, Matthew, Zhao, Sizheng Steven, Alam, Uazman and Cuthbertson, Daniel J (2024) Denosumab, for osteoporosis, reduces the incidence of type 2 diabetes, risk of foot ulceration and all-cause mortality in adults, compared with bisphosphonates: An analysis of real-world, cohort data, with a systematic review and meta-analysis. Diabetes, obesity & metabolism, 26 (9). pp. 3673-3683.

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Official URL: http://dx.doi.org/10.1111/dom.15708

Abstract

<h4>Aim</h4>To evaluate the impact of denosumab on (i) the incidence of type 2 diabetes (T2D), and (ii) long-term health outcomes (microvascular [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.<h4>Methods</h4>A retrospective analysis of data in a large global federated database (TriNetX; Cambridge, MA) 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 healthcare organizations. Propensity score matching (1:1) of confounders was undertaken that resulted in 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 the association between denosumab and T2D. Estimates were pooled using random-effects meta-analysis. Risk of bias and evidence quality were assessed using Cochrane-endorsed tools.<h4>Results</h4>Denosumab (vs. bisphosphonates) was associated with a lower risk of incident T2D over 5 years (hazard ratio 0.83 [95% confidence interval {CI} 0.78-0.88]). Secondary analysis showed 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 randomized 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]) (I<sup>2</sup> = 10.76%).<h4>Conclusions</h4>This is the largest cohort study to show that denosumab treatment is associated with a reduced RR of incident T2D, as well as an associated reduced RR of all-cause mortality and microvascular complications, findings that may influence guideline development in the treatment of osteoporosis, particularly in patients who are at a high risk of T2D.

Item Type:	Article
Uncontrolled Keywords:	Humans, Osteoporosis, Diabetic Foot, Diabetes Mellitus, Type 2, Diphosphonates, Incidence, Retrospective Studies, Cohort Studies, Adult, Aged, Middle Aged, Female, Male, Bone Density Conservation Agents, Denosumab
Depositing User:	Symplectic Admin
Date Deposited:	25 Jun 2024 09:44
Last Modified:	16 Aug 2024 22:26
DOI:	10.1111/dom.15708
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3182378