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Clinical Articles, Lead Article

SGLT-2 inhibitors: a game changer?

The results of the long awaited EMPA-REG (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes) trial were discussed by Dr Amar Puttanna (Young Diabetologists and Endocrinologists Forum, and West Midlands Deanery), then later mentioned in both the cardiology and renal trials updates, by Professor John Cleland (Imperial College, London) and Dr Patrick Mark (Queen Elizabeth University Hospital, Glasgow), respectively.

SGLT-2 inhibitors, such as empagliflozin, are thought to reduce the level of glucose reabsorption at the nephron, resulting in higher urinary glucose concentrations.1 However, no direct link has previously been shown between lowering serum glucose levels and cardiovascular risk. EMPA-REG has sought to investigate this issue, and the implications of this trial are certainly exciting for those working in both diabetes and cardiology.

Evidence published last year suggests an overwhelming benefit of empagliflozin in preventing cardiovascular disease in comparison to placebo.2 Although there was no difference in the incidence of stroke or myocardial infarction, there was evidence suggesting significantly lower rates of death from cardiovascular causes and lower rates of hospitalisation for symptoms associated with heart failure. Interestingly, the large population recruited already had evidence of cardiovascular disease, and a relative risk reduction of 38% for further cardiovascular events in such a high risk population is impressive.

Another major finding from this trial is the safety of empagliflozin in the long term. There were slight increased risks of genital and urinary tract infections, but no obvious deterioration in renal function. Given the safety and efficacy in reducing serum glucose and HbA1c levels, even in those with CKD Stage II & III,3 it is likely that SGLT-2 inhibitors would be particularly useful in patients with multiple co-morbidities, where other more diabetic medications come into trouble.

What’s more, there is increasing evidence from EMPA-REG to suggest that empagliflozin has a diuretic effect from increased glucose excretion, and this may be the reason for the improved outcomes in chronic heart failure patients, particularly lower rates of hospitalisation from symptoms.


1. Gallo LA, Wright EM, Vallon V. Probing SGLT2 as a therapeutic target for diabetes: basic physiology and consequences. Diab Vasc Dis Res 2015;12: 78–89.

2. Zinman B, Wanner C, Lachin JM et al. Empagliflozin, cardiovascular outcomes and mortality in type 2 diabetes. N Engl J Med 2015;373: 2117–28.

3. Barnett AH, Mithal A, Manassie J et al. Efficacy and safety of empagliflozin added to existing antidiabetes treatment in patients with type 2 diabetes and chronic kidney disease: a randomised, double-blind, placebo-controlled trial. LanDia 2014;2:369–84.

Published on: February 21, 2017

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