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SGLT-2 inhibitors: cardioprotective in patients with type 2 diabetes with or without CVD

By Nicole MacKee
Sodium­-glucose cotransporter­-2 (SGLT­2) inhibitors protect against cardiovascular (CV) events in patients with type 2 diabetes, regardless of their history of CVD, researchers have reported in the Journal of the American Heart Association.

The researchers, led by Dr Clare Arnott at the George Institute for Global Health, Sydney, completed a systematic review and meta-analysis of four trials of SGLT­2 inhibitors in patients with type 2 diabetes, in which three SGLT­2 inhibitors were evaluated (canagli­flozin, empagliflozin and dapagliflozin). The trials included 38,723 participants, of whom 22,870 (59%) had CV disease, 7754 (20%) had reduced kidney function and 4543 (12%) had heart failure.

The researchers found an overall 12% reduction in major adverse CV events in patients taking SGLT­2 inhibitors, compared with those taking placebo. Relative reductions in CV death (17%) and hospitalisations for heart failure (32%) were also found, but no overall effect on stroke risk.

The researchers reported that the cardioprotective effects were consistent across patient groups irrespective of CVD history, heart failure or reduced kidney function. Professor Jenny Gunton, Head of the University of Sydney’s Centre for Diabetes, Obesity and Endocrinology Research, said most SGLT­2 inhibitors appeared to be cardioprotective and, so far, all improved heart failure.

‘Dapagliflozin did not show any other cardiovascular benefit, however, and I would not select it for a person with pre­existing cardiovascular disease or for someone with a very high cardiac risk,’ she said, adding that, to date, all SGLT­2 inhibitors appeared to be kidney­protective.

Professor Gunton said that in the absence of contraindications to SGLT­2 inhibitors – mostly problematic thrush or recurrent urinary tract infections – these drugs should be considered for an add-on after metformin.

‘Metformin pre­dates the cardiovascular safety trials but is more effective for [lowering] HbA1c [levels] and is probably also cardioprotective,’ Professor Gunton told Medicine Today. ‘After metformin, then, [doctors] should individualise treatment and consider the next step. Our PBS guidelines will, of course, influence prescribing as they affect cost to the patient.’ She said lifestyle changes remained the best approach for type 2 diabetes and should be revisited with each progressive step in diabetes therapies.
J Am Heart Assoc. 2020; 9: e014908; doi: 10.1161/JAHA.119.014908.