OBJECTIVES: Going beyond their initial use as antidiabetic agents, sodium-glucose cotransporter-2 (SGLT2) inhibitors have certified their roles in the treatment of other chronic diseases independent from diabetes. We aim to demonstrate how the positions of SGLT2 inhibitors have changed in the treatment algorithms of type 2 diabetes (T2DM), heart failure (HF), and chronic kidney disease (CKD), and which opportunities lie in the future.

METHODS: A targeted review was performed. International guidelines for T2DM, HF, and CKD published from 2012 onward were included for the analysis of positioning. An advanced search on clinicaltrials.gov was conducted to identify recently published and ongoing trials of SGLT2 inhibitors in related diseases to analyse their possible positions in the future.

RESULTS: Established evidence of cardiorenal protective benefits of these drugs has placed SGLT2 inhibitors as first-line monotherapy agents in T2DM patients with related comorbidities. Both dapagliflozin and empagliflozin are recommended in the combined therapy of chronic HF due to their clinical efficacy and cost-effectiveness. While dapagliflozin already has proven its place in the treatment algorithm of CKD, empagliflozin might share a similar position based on the early termination of the EMPA-KIDNEY trial due to clear positive results in patients with CKD. Furthermore, the cardiorenal benefits of SGLT2 inhibitors regardless of diabetic status are being investigated in ongoing trials looking at the efficacy and safety in patients with acute HF, myocardial infarction, and severe CKD, including dialysis and kidney transplantation.

CONCLUSIONS: Despite emerging evidence however, prescriptions of SGLT2 inhibitors are lagging. Their limited usage within T2DM at present and potentially slow adaptation in HF and CKD hinders treatment and protection in these patients, resulting in potential losses in health benefits, measured by quality-adjusted life years. This suggests that policy makers should be attentive to their uptake among eligible patients since their protective evidence has already been established.