The safety of sodium–glucose cotransporter-2 inhibitors in people with chronic kidney disease and type 2 diabetes

There is a paucity of safety data on the use of sodium–glucose cotransporter-2 (SGLT2) inhibitors in patients with chronic kidney disease (CKD) and type 2 diabetes. This is of concern because people with CKD already have a higher baseline risk for fractures and lower-limb amputations, which have been reported in some trials as a side effect of SGLT2 inhibitors. This population-based cohort study from the US aimed to determine the safety profile of this medication by studying over 57,000 people with type 2 diabetes and CKD who were initiated for the first time on either an SGLT2 inhibitor or a glucagon-like peptide-1 (GLP-1) receptor agonist. The mean age across both groups was 72 years, 56% were men and 64% were White.

In the 1:1 propensity-score matched cohort, SGLT2 inhibitor initiators had a higher risk of non-vertebral fractures (HR, 1.30 [95% CI, 1.03–1.65]; incidence rate difference, 2.13 [95% CI, 0.28–3.97]), lower-limb amputations (1.65 [1.22–2.23]; 2.46 [1.00–3.92]) and genital infections (3.08 [2.73–3.48]; 41.26 [37.06–45.46]). The absolute risk increase for these safety outcomes was small: 2.1 more lower-limb amputations and 2.5 more fractures per 1000 people receiving SGLT2 inhibitors compared with those on GLP-1 receptor agonists. No noticeable differences were observed for the other safety outcomes, including DKA, hypovolaemia, hypoglycaemia and severe urinary tract infection. Of note, the higher risk for lower-limb amputations and non-vertebral fractures was not observed when using dipeptidyl peptidase-4 inhibitors as an alternative comparator.

The authors conclude that these safety data can help inform patient–physician decision-making regarding risks and benefits of SGLT2 inhibitors in this population. Consideration should be given to the limitations of the study, which included a short follow-up time.

The full study can be read here.