Certain Diabetes Medications Raise Risk of Amputation

Some medications for diabetes may come with the increased odds of lower limb amputation, according to a recent study. 

In the register-based cohort study, published in The BMJ, researchers compared the use of sodium glucose cotransporter 2 (SGLT2) inhibitors to glucagon-like peptide 1 (GLP1) receptor agonists. Between July 2013 and December 2016, 17,213 new users of SGLT2 inhibitors (dapagliflozin, 61%; empagliflozin, 38%; canagliflozin, 1%) were propensity score-matched to 17,213 new GLP1 receptor agonists users. In addition to lower limb amputation, the other primary outcomes were bone fracture, diabetic ketoacidosis, acute kidney injury, serious urinary tract infection, venous thromboembolism, and acute pancreatitis. 

Patients using SGLT2 inhibitors had increased odds of lower limb amputation than those using GLP1 receptor agonists (incidence rate [IR] 2.7 vs. 1.1 events per 1,000 person years; hazard ratio [HR] 2.32; 95% confidence interval [CI] 1.37-3.91), and were at increased risk of diabetic ketoacidosis (IR 1.3 vs. 0.6; HR 2.14; 95% CI 1.01-4.52). Researchers did not associate increased risk of bone fracture (IR 15.4 vs. 13.9; HR 1.11; CI 95% 0.93-1.33), acute kidney injury (IR 2.3 vs. 3.2; HR 0.69; 95% CI 0.45-1.05), serious urinary tract infection (IR 5.4 vs. 6.0; HR 0.89; 95% CI 0.67-1.19), venous thromboembolism (IR 4.2 vs. 4.1; HR 0.99; 95% CI 0.71-1.38), or acute pancreatitis (IR 1.3 vs. 1.2; HR 1.16; 95% CI 0.64-2.12). 

Certain patients should be watched carefully if their treatment regimen includes SGLT2 inhibitors, said lead study author Dr. Peter Ueda, a postdoctoral researcher of Karolinska University Hopsital in Stockholm, Sweden. 

“Patients at high risk of amputation, for example those with peripheral artery disease or foot ulcers, might be monitored more closely if SGLT2 inhibitors are used, and the risk of this adverse event may be considered when deciding on which drugs to use,” Ueda said. 

One of the study’s limitations is its observational nature, and while Ueda and his colleagues took several variables into consideration, unaccounted factors may play a role as well. 

“Although we used a strict study design and accounted for a large number of patient-related variables in our analyses, the results could be affected by unmeasured differences in the characteristics of the patients receiving SGLT2 inhibitors vs. the comparator drug,” Ueda said. “This is always the case with observational studies and the reason why findings from such studies should be considered with caution.” 

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SourcesThe BMJ, HealthDay