Use of sodium-glucose co-transporter 2 inhibitors, changes in body mass index and risk of fracture: a population-based cohort study

Judith van Dalem, Nikki C. C. Werkman, Joop P. van den Bergh, Bernardette Rossi, Rikke Viggers, Richard Eastell, Andrea M Burden, Coen D. A. Stehouwer, Olaf H Klungel, Martijn C. G. J. Brouwers, Johanna H.M. Driessen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

AIMS: Sodium-glucose co-transporter-2 (SGLT-2) inhibitor-induced weight loss might play a role in the debated elevated fracture risk with these agents. The aim of the current study was to investigate the association between SGLT-2 inhibitor use, changes in body mass index (BMI) and fracture risk.

METHODS: A retrospective cohort study was conducted using data from the UK Clinical Practice Research Datalink (CPRD) GOLD (2013-2018). The study population (N=34,960) consisted of adults with diabetes initiating a sulphonylurea or SGLT-2 inhibitor. Cox proportional hazards models estimated hazard ratios (HRs) for major osteoporotic fracture with SGLT-2 inhibitor use versus sulphonylurea use, stratified by change in BMI, average daily dose and cumulative dose. Analyses were adjusted for age, sex, lifestyle variables, comorbidities, and concomitant drug use.

RESULTS: SGLT-2 inhibitor use was not associated with an increased fracture risk compared to sulphonylurea use (adjusted HR 1.19; 95% confidence interval (CI): 0.80-1.79). This finding remained consistent after stratification by BMI change. However, the highest cumulative dose category was associated with an increased fracture risk (adjusted HR: 2.10, 95%CI: 1.11-3.99).

CONCLUSION: SGLT-2 inhibitor use was not associated with increased osteoporotic fracture risk, irrespective of change in BMI. However, a high cumulative dose could be an important risk factor.

Original languageEnglish
Article number109993
Number of pages8
JournalDiabetes Research and Clinical Practice
Volume190
Early online date13 Jul 2022
DOIs
Publication statusPublished - Aug 2022

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