Diabetes medications with cardiovascular protection – what now after LEADER®? Could metformin, pioglitazone, empagliflozin and liraglutide complement each other to save lives?
Abstract
formin, pioglitazone and empagliflozin would likely improve cardiovascular outcomes in patients with type 2 diabetes at high cardiovascular risk.1 This conclusion was 15 years in the making: 7 years between the UK Prospective Diabetes Study (UKPDS) in 19982 and the PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive) study in 2005,3 and then another 8 years from there to the landmark moment when we saw the results of the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes trial (EMPA-REG OUTCOMETM) at the European Association for the Study of Diabetes (EASD) 2015 in Stockholm.4,5 Against this background, it is remarkable that we needed to wait only another 9 months for a similar moment at American Diabetes Association (ADA) 2016 in New Orleans. This 4th landmark event, when the finding shown in Figure 1 was greeted with loud applause, was the presentation of the results of the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER®) study, which evaluated the effect of the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide on cardiovascular outcomes in people with type 2 diabetes at high cardiovascular risk.6,7 Once again though, as the results unfolded, we realised that we were to be left with as many questions as answers. Our previous editorial concluded that the accumulated evidence from multiple studies suggests that pioglitazone (PROactive) probably exerts its beneficial…
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