Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2023 Apr 18:381:e073435.
doi: 10.1136/bmj-2022-073435.

Denosumab and incidence of type 2 diabetes among adults with osteoporosis: population based cohort study

Houchen Lyu  1   2   3 , Sizheng Steven Zhao  4 , Licheng Zhang  1   3 , Jie Wei  5   6 , Xiaoxiao Li  2 , Hui Li  2 , Yi Liu  7 , Pengbin Yin  1   3 , Vibeke Norvang  8 , Kazuki Yoshida  9 , Sara K Tedeschi  9 , Chao Zeng  2   10   11 , Guanghua Lei  12   10   11 , Peifu Tang  13   3 , Daniel H Solomon  14   15
Affiliations
Comparative Study

Denosumab and incidence of type 2 diabetes among adults with osteoporosis: population based cohort study

Houchen Lyu et al. BMJ. .

Abstract

Objective: To estimate the effect of denosumab compared with oral bisphosphonates on reducing the risk of type 2 diabetes in adults with osteoporosis.

Design: Population based study involving emulation of a randomized target trial using electronic health records.

Setting: IQVIA Medical Research Data primary care database in the United Kingdom, 1995-2021.

Participants: Adults aged 45 years or older who used denosumab or an oral bisphosphonate for osteoporosis.

Main outcome measures: The primary outcome was incident type 2 diabetes, as defined by diagnostic codes. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals, comparing denosumab with oral bisphosphonates using an as treated approach.

Results: 4301 new users of denosumab were matched on propensity score to 21 038 users of an oral bisphosphonate and followed for a mean of 2.2 years. The incidence rate of type 2 diabetes in denosumab users was 5.7 (95% confidence interval 4.3 to 7.3) per 1000 person years and in oral bisphosphonate users was 8.3 (7.4 to 9.2) per 1000 person years. Initiation of denosumab was associated with a reduced risk of type 2 diabetes (hazard ratio 0.68, 95% confidence interval 0.52 to 0.89). Participants with prediabetes appeared to benefit more from denosumab compared with an oral bisphosphonate (hazard ratio 0.54, 0.35 to 0.82), as did those with a body mass index ≥30 (0.65, 0.40 to 1.06).

Conclusions: In this population based study, denosumab use was associated with a lower risk of incident type 2 diabetes compared with oral bisphosphonate use in adults with osteoporosis. This study provides evidence at a population level that denosumab may have added benefits for glucose metabolism compared with oral bisphosphonates.

PubMed Disclaimer

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: no support from any organization for the submitted work; DHS receives salary support from unrelated research contracts to his institution from Abbvie, Amgen, CorEvitas, Janssen, and ModernaTx; SSZ receives lecture honorariums and participates on the medical advisory board from Union Chimique Belge; KY receives consulting fees from OM1; and no other relationships or activities that could appear to have influenced the submitted work.

Figures

Fig 1
Fig 1
Study flow diagram. IMRD=IQVIA Medical Research Data. *Participants could enter the study cohort a maximum of twice: first with an oral bisphosphonate and second when initiating denosumab. †Matched with replacement (also see method section in the supplemental file)
Fig 2
Fig 2
Cumulative incidence of type 2 diabetes as defined by diagnostic codes and by an alternative definition combining diagnostic codes, antidiabetes drugs, and laboratory test results among users of denosumab and matched users of bisphosphonates in IQVIA Medical Research Data. Shaded areas represent 95% confidence intervals (CIs)
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Cummings SR, San Martin J, McClung MR, et al. FREEDOM Trial . Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361:756-65. 10.1056/NEJMoa0809493. - DOI - PubMed
    1. Lacey DL, Boyle WJ, Simonet WS, et al. . Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab. Nat Rev Drug Discov 2012;11:401-19. 10.1038/nrd3705. - DOI - PubMed
    1. Eastell R, Rosen CJ, Black DM, Cheung AM, Murad MH, Shoback D. Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab 2019;104:1595-622. 10.1210/jc.2019-00221. - DOI - PubMed
    1. Gregson CL, Armstrong DJ, Bowden J, et al. . UK clinical guideline for the prevention and treatment of osteoporosis. Arch Osteoporos 2022;17:58. 10.1007/s11657-022-01061-5. - DOI - PMC - PubMed
    1. Buckley L, Guyatt G, Fink HA, et al. . 2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis. Arthritis Rheumatol 2017;69:1521-37. 10.1002/art.40137. - DOI - PubMed

Publication types