Analysis Looks at SGLT2 Inhibitors Across Diabetes, Heart Failure, CKD

Sodium-glucose transporter 2 (SGLT2) inhibitors decrease the risk of acute kidney injury and severe hypoglycemia for those with diabetes, heart failure, and chronic kidney disease (CKD) but increase the risk of diabetic ketoacidosis.

Sodium-glucose transporter 2 (SGLT2) inhibitors decrease the risk of acute kidney injury and severe hypoglycemia for patients of 3 chronic diseases but increase the risk of diabetic ketoacidosis and other complications, a new study found.

Previous studies have assessed the safety profile of SGLT2 inhibitors in type 2 diabetes (T2D). The meta-analysis published in Diabetes and Vascular Disease Research was the first to assess the safety of these drugs not only in T2D but chronic kidney disease and chronic heart failure, the authors said.

Results showed the treatment with SGLT2 inhibitors vs. placebo reduced the risk of acute kidney injury (risk ratio [RR] 0.75; 95% CI, 0.66-0.85) and severe hypoglycemia (RR, 0.86; 95% CI, 0.71-1.03).

However, SGLT2 inhibitors vs. placebo significantly increased the risks of diabetic ketoacidosis (RR, 2.57; 95% CI, 1.53-4.31; P for drug effect <.001); genital infection (RR, 3.75; 95% CI, 3.00-4.67; P <.001); and volume depletion (RR, 1.14; 95% CI, 1.05-1.24; P = .002).

There were also trends toward increased risk of fracture (RR, 1.07; 95% CI, 0.99-1.16; P = .081); amputation (RR, 1.21; 95% CI, 0.97-1.51; P = .085), and urinary tract infection (RR, 1.07; 95% CI, 0.99-1.15; P = .074).

The findings are meant to guide clinicians in monitoring for these adverse events when treating patients with SGLT2 inhibitors, the authors said. Results of previous studies on the safety of SGLT2 inhibitors, which focused solely on T2D, produced inconsistent results.

The meta-analysis evaluated 8 randomized clinical trials and assessed 4 SGLT2 inhibitors: dapagliflozin, empagliflozin, ertugliflozin (Steglatro), and canagliflozin. The authors indicated that the evaluation of the safety profiles was consistent across all 3 diseases studied.

The authors said the meta-analysis was strong because all the original studies were high quality. One weakness, however, was that the patients in the studies had considerably different baseline characteristics, including the comorbidities involved. They recommended further studies to minimize ascertainment bias.

Three of the studies used in the meta-analysis were recent: DAPA-CKD, EMPEROR-Reduced, and VERTIS CV.


Qiu M, Ding L-L, Zhang M, et al. Safety of four SGLT2 inhibitors in three chronic diseases: A meta-analysis of large randomized trials of SGLT2 inhibitors. Diab Vasc Dis Res. Published online April 22, 2021. doi:10.1177/14791641211011016

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