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Diabetes drug selections can influence cardiovascular outcomes

By Bianca Nogrady
Individuals with type 2 diabetes (T2DM) and pre-existing cardiovascular disease (CVD) may derive additional cardiovascular benefits from sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists used for blood glucose control, Italian researchers suggest.

A meta-analysis and systematic review, published in the Journal of the American Heart Association, analysed 12 randomised controlled trials of cardiovascular outcomes in adults with T2DM, comparing add-on diabetes therapies. The study also examined four major intensive glycaemic control trials to assess the impact of improving blood glucose levels on major adverse cardiovascular events (MACE).

The analysis of the large intensive glycaemic control trials suggested that glycaemic control by itself had a small role in reducing the cardiovascular impact of type 2 diabetes, compared with the beneficial effect on microvascular complications such as retinopathy.

However, the meta-analysis of specific cardiovascular outcome trials did find a reduced risk of MACE but only in patients with CVD at baseline.

This benefit was particularly associated with GLP-1 receptor agonists and SGLT-2 inhibitors, which were each associated with a significant 14% lower risk of MACE in patients with pre-existing CVD compared with placebo.

The authors wrote that GLP-1 receptor agonists beneficially impacted a range of cardiovascular risk factors such as weight and appetite, blood pressure and lipid profile. SGLT-2 inhibitors achieved body weight and fat mass reductions through glycosuria, increased natriuresis and uricosuria, which could lead to better cardiovascular and renal outcomes.

‘Because the prevalence of CVD in the T2DM population may range from 24% (real-world) to 100% (cardiovascular outcome trials), at least one fourth of the average T2DM outpatients are possible candidates for the use of the newer glucose-lowering medications demonstrated to improve the MACE outcome,’ they wrote.

Commenting on the findings, Professor Lesley Campbell, Clinician Specialist in Endocrinology at the Diabetes Centre at St Vincent’s Hospital and the Garvan Institute, Sydney, said the paper was important in examining the nitty-gritty of how newer diabetes drugs compared with the established diabetes drugs as regards cardiovascular outcomes.

Professor Campbell told Endocrinology Today that although it was well known that diabetes increased cardiovascular risk, this analysis clarified the limits of improving glycaemic control alone. ‘Also, it shows that we should be using something more now that these cardioprotective diabetes drugs are available, demonstrably benefiting those with prior CVD and in the case of SGLT2 inhibitors even lessening heart failure and renal disease in those without known pre-existing CVD.’
J Am Heart Assoc 2019; 8: e012356.