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
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.