(HealthDay News) — Use of sodium glucose cotransporter 2 (SGLT2) inhibitors is associated with an increased risk for lower-limb amputation and diabetic ketoacidosis compared with use of glucagon-like peptide 1 (GLP1) receptor agonists, according to a study published online in The BMJ.

Peter Ueda, MD, PhD, from Karolinska University Hospital in Stockholm, and colleagues examined the correlation between SGLT2 inhibitors and serious adverse events of current concern in a register-based cohort study. Data were included for a propensity score-matched cohort of 17,213 new users of SGLT2 inhibitors and 17,213 new users of GLP1 receptor agonists.

The researchers found that compared with GLP1 receptor agonists, use of SGLT2 inhibitors correlated with an increased risk for lower-limb amputation (incidence rate ratio, 2.7 vs 1.1 events per 1000 person-years; hazard ratio [HR], 2.32; 95% confidence interval [CI], 1.37 to 3.91) and diabetic ketoacidosis (1.3 vs 0.6; HR, 2.14; 95% CI, 1.01 to 4.52). SGLT2 use was not associated with increased risks for bone fracture (15.4 vs 13.9; HR, 1.11; 95% CI, 0.93 to 1.33), acute kidney injury (2.3 vs 3.2; HR, 0.69; 95% CI, 0.45 to 1.05), serious urinary tract infection (5.4 vs 6.0; HR, 0.89; 95% CI, 0.67 to 1.19), venous thromboembolism (4.2 vs 4.1; HR, 0.99; 95% CI, 0.71 to 1.38), or acute pancreatitis (1.3 vs 1.2; HR, 1.16; 95% CI, 0.64 to 2.12).

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“The findings should be interpreted in the context of limitations of observational studies and the uncertainty of the effect estimates,” the authors write.

Several authors disclosed financial ties to the pharmaceutical industry.

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Ueda P, Svanström H, Melbye M, et al. Sodium glucose cotransporter 2 inhibitors and risk of serious adverse events: nationwide register based cohort study. BMJ 2018;363. DOI:10.1136/bmj.k4365 (Published online November 14, 2018)