Outcome trial data on sodium glucose cotransporter-2 inhibitors: Putting clinical benefits and risks in perspective

Abstract

BackgroundSodium glucose cotransporter-2 (SGLT2) inhibitors have significant heart failure and renoprotective benefits with a wide spectrum of unfamiliar and potentially serious adverse effects. Limited understanding of the risk-benefit profile of SGLT2 inhibitor treatment may result in under utilisation by prescribers and patients. MethodsData from recent seminal randomized, placebo-controlled, outcome trials for multiple SGLT2 inhibitors were incorporated. Trial populations were sub-classified into high cardiovascular risk T2DM, HFrEF, and CKD. Efficacy outcomes of heart failure hospitalisation (HFH), cardiovascular (CV) mortality, total mortality, and prevention of renal deterioration were examined. Safety outcomes included were major hypoglycaemia, diabetic ketoacidosis (DKA), urinary tract infections (UTI), mycotic genital infections (MGI), hypotension, amputations and fractures. Absolute risk reduction/increase were used to calculate number needed to treat/harm. ResultsTrial data comprised 71,545 patients, of which 53,144 were high risk T2DM, 9696 HFrEF and 8705 CKD. For HFrEF, NNT for HFH was 18, CV mortality 93, total mortality 76, prevention of renal deterioration 143 and prevention of DKA 6224. NNH for UTI was 557, MGI 356, hypotension 120, hypoglycaemia 574, amputations 707 and fractures 858. For CKD, NNT for HFH was 116, CV mortality 245, total mortality 138, and prevention of renal deterioration was 63. NNH for DKA was 1458, UTI 309, MGI 291, hypotension 165, hypoglycaemia 374, amputations 4450 and fractures 696. In the T2DM cohort, NNT for HFH was 139, CV mortality 851, total mortality 601 and prevention of renal deterioration 558. NNH DKA was 1525, UTI 239, MGI 69, hypotension 325, hypoglycaemia 472, amputations 1578 and fractures 9569. Conclusions and relevanceThe cardiovascular and renal protective benefits of SGLT2 inhibitors far outweigh the risks. This paper puts into perspective the benefits and risks of treatment with SGLT2 inhibitors for clinicians and patients.