Risk of Incident Type 2 Diabetes with Romosozumab Versus Denosumab in Patients with Osteoporosis: A Global Real-World Cohort Study - 04/11/26

Doi : 10.1016/j.diabet.2026.101803

Chui-Jia Farn ^1,^{^{#
The first two authors contributed equally as co-first authors.}} , I-Ching Chiang ^2,^{^{#
The first two authors contributed equally as co-first authors.}} , Hung-Kuan Yen ^1,³ , Mao-Yi Yang ⁴ , I-Hsin Chen ^1,⁴ , I-Weng Yen ⁷ , Tzu-Hao Tseng ^1,^⁎ , Shau-Huai Fu ^1,⁵ , Chen-Yu Wang ^5,⁶

¹ Department of Orthopedic Surgery, National Taiwan University Hospital, No. 7, Zhongshan S. Rd., Zhongzheng Dist, Taipei City 100225, Taiwan R.O.C.

² Department of Medical Education, National Taiwan University Hospital, No. 1, Sec. 1, Ren'ai Rd., Zhongzheng Dist, Taipei City 100233, Taiwan R.O.C

³ Department of Orthopedic Surgery, National Taiwan University Hospital, Hsinchu branch, No. 25, Ln. 442, Sec. 1, Jingguo Rd., North Dist, Hsinchu City 300197, Taiwan R.O.C

⁴ Department of Orthopedic Surgery, Shin Kong Wu Ho-Su Memorial Hospital, No. 95, Wenchang Rd., Shilin Dist, Taipei City 111045, Taiwan R.O.C

⁵ Department of Orthopedic Surgery, National Taiwan University Hospital, Douliu branch, No. 579, Sec. 2, Yunlin Rd., Douliu City, Yunlin County 640203, Taiwan R.O.C

⁶ Department of Pharmacy, National Taiwan University Hospital Yun-Lin Branch, National Center for Geriatrics and Welfare Research, National Health Research Institutes, No. 579, Sec. 2, Yunlin Rd., Douliu City, Yunlin County 640203, Taiwan R.O.C

⁷ Division of Endocrinology, Department of Internal Medicine, National Taiwan University Hospital, No. 7, Zhongshan S. Rd., Zhongzheng Dist, Taipei City 100225, Taiwan R.O.C

^⁎ Corresponding author: Tzu-Hao Tseng, Department of Orthopedic Surgery, National Taiwan University Hospital, No. 7, Zhongshan S. Rd., Zhongzheng Dist, Taipei City 100225, Taiwan R.O.C Department of Orthopedic Surgery National Taiwan University Hospital No. 7, Zhongshan S. Rd., Zhongzheng Dist Taipei City R.O.C 100225 Taiwan

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Highlights

•	Romosozumab was not associated with increased incident T2D risk versus denosumab.
•	Broader diagnostic, medication, and laboratory outcomes showed similar findings.
•	Calendar-year analyses showed no evidence of treatment effect heterogeneity.
•	Most subgroup and sensitivity analyses were consistent with the primary result.

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Abstract

Background

Antiosteoporotic agents may influence glucose regulation. Although denosumab has been evaluated for its potential effects on diabetes-related outcomes, the metabolic effects of romosozumab, a sclerostin inhibitor, remains unclear.

Methods

This retrospective cohort study included patients aged ≥45 years with osteoporosis and no prior diabetes who initiated romosozumab or denosumab between 2019 and 2024 from the TriNetX network. An active-comparator, new-user design compared romosozumab users with denosumab users. The primary outcome was incident type 2 diabetes (T2D). Secondary outcomes included broader diabetes diagnoses, initiation of antidiabetic medications, and laboratory-defined diabetes. Treatment groups were balanced using 1:1 propensity score matching (PSM). Cox proportional hazards models, Kaplan–Meier analyses with log-rank tests, calendar time analyses, and multiple sensitivity analyses were performed.

Results

After propensity score matching, 6581 patients were analyzed in each treatment group. Romosozumab initiation was not associated with a significant difference in incident T2D compared with denosumab (HR, 0.93; 95% CI, 0.78–1.12; log-rank p = 0.468). Similarly, no significant differences were observed for broader diabetes diagnoses (HR, 1.01; 95% CI, 0.86–1.20), antidiabetic medication initiation (HR, 1.15; 95% CI, 0.95–1.40), or laboratory-defined diabetes (HR, 0.97; 95% CI, 0.77–1.21).

Conclusions

Romosozumab was not associated with an increased risk of incident T2D or other diabetes-related outcomes compared with denosumab. These findings were supported by calendar-year-specific analyses, although residual confounding and differential follow-up warrant cautious interpretation. Future prospective studies are needed to clarify the metabolic effects of sclerostin inhibition.

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Keywords : Denosumab, Osteoporosis, Romosozumab, Type 2 diabetes