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08-09-2017 | Sodium-glucose co-transporter-2 inhibitors | News

Support for cardioprotective effects of SGLT2 inhibitors

medwireNews: Patients with type 2 diabetes receiving treatment with sodium-glucose co-transporter-2 (SGLT2) inhibitors have a lower risk for adverse cardiovascular outcomes than those using other glucose-lowering drugs, results from the CVD-REAL Nordic study suggest.

As reported in The Lancet Diabetes & Endocrinology, Johan Bodegård (AstraZeneca Nordic-Baltic, Oslo, Norway) and colleagues analyzed individual patient-level data from almost 100,000 patients with a mean age of 61 years and a cardiovascular disease (CVD) prevalence of 25%, using national registry data from Norway, Sweden, and Denmark.

These countries “have complete population-level registries with full records of disease history and mortality causes,” that can be used “to investigate a broad range of cardiovascular outcomes in real-world settings,” explain Bodegård and team.

Over a mean follow-up of 10.8 months , 0.25% of 22,830 patients receiving treatment with SGLT2 inhibitors died from cardiovascular causes, compared with 0.50% of 68,490 matched participants receiving other glucose-lowering drugs, giving corresponding event rates of 0.27 and 0.53 per 100 patient–years and a significant hazard ratio (HR) of 0.53.

Similarly, patients receiving SGLT2 inhibitors were significantly less likely to experience major adverse cardiovascular events (MACE) – defined as cardiovascular mortality, myocardial infarction, or stroke – than those receiving other glucose-lowering drugs, with rates of 1.48% versus 1.97% and 1.64 versus 2.12 events per 100 patient–years (HR=0.78).

“The present data extend the results of [the EMPA-REG OUTCOME and CANVAS trials] to the SGLT2 inhibitor drug class and to a real-world clinical setting in an unselected type 2 diabetes population with a broad cardiovascular risk profile,” say the study authors.

However, they caution that because “dapagliflozin was much more widely used than other SGLT2 inhibitor drugs” in the study, accounting for more than 90% of the SGLT2 inhibitor exposure time, “potential differences between different SGLT2 inhibitors could not be assessed.”

The author of an accompanying comment, David Fitchett (St Michael’s Hospital, Toronto, Ontario, Canada), agreed with Bodegard and team, and noted that “the results must be considered within the limitations of observational studies,” but he believes that the reductions in adverse cardiovascular outcomes were “impressive,” and provide “some additional support for a class effect for SGLT2 inhibitors.”

An additional study by the CVD-REAL Nordic team, published in Diabetes, Obesity and Metabolism, provided further evidence for the cardioprotective effects of SGLT2 inhibitors. In this study, Frederik Persson (Steno Diabetes Center Copenhagen, Denmark) and colleagues compared dapagliflozin with dipeptidyl peptidase (DPP)‐4 inhibitors, “a specific and clinical[ly] relevant treatment strategy.”

The team found that 10,227 type 2 diabetes patients treated with dapagliflozin had a significantly lower risk for MACE, heart failure, and all-cause mortality than the 30,681 participants receiving DPP‐4 inhibitors over a mean follow-up of 0.95 years, with corresponding HRs of 0.79, 0.62, and 0.44.

“As evidence-based treatment of heart failure in [type 2 diabetes] is currently lacking, these new findings might be of particular clinical importance while waiting for results from ongoing randomized mechanistic and outcome trials of dapagliflozin,” write Persson and colleagues.

Nevertheless, the authors of both CVD-REAL Nordic studies emphasize that randomized trial results are required to validate their findings.

And David Fitchett concludes: “Only with the results of the DECLARE-TIMI 58 study, due in 2019, will we have definitive evidence for the cardiovascular benefit and safety of dapagliflozin.”

By Claire Barnard

medwireNews is an independent medical news service provided by Springer Healthcare. © 2017 Springer Healthcare part of the Springer Nature group

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