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SGLT2 inhibitors with metformin do not influence fracture risk

Key clinical point: Sodium-glucose transporter-2 inhibitors (SGLT2is) combined with metformin therapy did not influence fracture risk in patients with type 2 diabetes mellitus (T2DM).

Major finding: SGLT2is and metformin combination therapy did not increase the risk of fracture vs. metformin monotherapy or other comparators in patients with T2DM (odds ratio, 0.97; 95% confidence interval, 0.71-1.32).

Study details: A meta-analysis of 25 randomized controlled trials including 19,500 participants with T2DM.

Disclosures: No study sponsor was identified. The authors declared no conflicts of interest.


“Type 2 diabetes mellitus (T2DM) is associated with an increase in fracture risk, despite normal or even higher bone mineral density (BMD) measurements. Antidiabetic drugs can have variable effects on bone, with some drugs increasing fracture risk (e.g., thiazolidinediones, sulfonylureas, insulin), while others positively impacting bone health (e.g., dipeptidyl peptidase-4 inhibitors, glucagonlike peptide- receptor agonists, metformin). Combination therapy of sodium-glucose transporter-2 inhibitors (SGLT2is) and metformin therapy is an attractive option for patients with T2DM, particularly those with cardiovascular and renal disease.

This meta-analysis of 25 randomized controlled trials (RCTs) included 19,500 participants with T2DM and evaluated the association between combined treatment with SGLT2is and metformin for T2DM and fracture risk. Over a trial duration ranging from 24 to 208 weeks, a total of 88 incident fractures (0.91%) occurred among 9662 patients who received SGLT2is combined with metformin there were, while 79 (0.80%) incident fractures were observed among 9838 patients with T2DM who received other active comparators. Thus, the risk for fracture in patients with T2DM was similar in the SGLT2is and metformin combination therapy group vs other active comparators. The included RCTs were of high quality and no heterogeneity was noted (I2 = 0%, P = 0.86). These results are reassuring for patients with T2DM who use SGLT2is and metformin combination therapy.”

Maria I. Danila, MD, MSc, MSPH

University of Alabama at Birmingham


Qian BB et al. Osteoporos Int. 2020 Aug 11. doi: 10.1007/s00198-020-05590-y.