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2015 congress in Stockholm, were aware that this was one of those landmark moments in the history of diabetes care. There was loud applause. The event was the presentation of the results of the EMPA-REG OUTCOME study, which evaluated the effect of the SGLT2 inhibitor, empagliflozin, on cardiovascular outcomes in peo ple with type 2 diabetes at high cardiovascular risk. 1,2 As the whole story of the results unfolded, however, we realised that we were going to be left with as many questions as answers. In particular it seemed that empagliflozin reduced death from cardiac causes but did not reduce non-fatal myocardial infarction or stroke, a combination of findings which was at first sight difficult to understand. Comparing and contrasting the graphs from EMPA-REG, such as the one shown in Figure 1, with those from other studies is a quick way of getting a feel for the subject of antihyperglycaemic med ications that might play a part in reducing cardiovascular risk. Figure 2 shows the Kaplan-Meier plots for metformin in the 10-year, observational follow-up of the United Kingdom Prospective Diabetes Study (UKPDS), 3 which suggested the value of metformin as a cardioprotective agent seen in the earlier, randomised phase of the study. 4 Intensive glycaemic management with metformin, but not with a sulphonylurea or insulin, reduced cardiovascular out comes, in comparison with the conventional (mainly diet-based) management of the time, during the original trial. 3,4 The fact that this occurred even though there was less reduction in HbA 1c in the metformin group (who were overweight) than the sulphonylureainsulin group points to a special effect of metformin over and above any effect on glycaemic control. 3,4 It is noteworthy however that it took at least 3 years before the curves shown in Figure 2 for metformin really started to separate with regard to myocardial infarction or death from any cause. The patients in the UKPDS were

the british journal of diabetes and vascular disease

Diabetes medications with cardiovascular protection in the wake of EMPA-REG OUTCOME: the optimal combination may be metformin, pioglitazone and empagliflozin