by Mark Cooper, MB, BS, PhD

The VERTIS trial builds on other cardiovascular outcome trials which have confirmed the non-inferiority of the SGLT2 inhibitor class versus placebo on cardiovascular events in type 2 diabetic subjects. The study compared 2 doses of ertugliflozin versus placebo in a secondary prevention study of type 2 dibetic subjects with evidence of cardiovascular disease. The study demonstated non-inferiority versus placebo but was not associated with a reduction in 3P-MACE, an endpoint that was positive in some but not all the CVOT trials performed previously with this class of drugs. Nevertheless there was a reduction in hospitalisation for heart failure, the effect similar to that previously reported with empagliflozin, canagliflozin and dapagliflozin in the EMPA-REG, CANVAS and DECLARE trials respectively. These effects were seen in the context of known actions of these agents including a reduction in HbA1c, body weight and blood pressure. The effects on renal endpoints are more difficult to interpret with a trend towards a reduction in a composite of renal endpoints. Comparisons with other trials are not easy to perform with other studies varying in which renal composite endpoint was used, some studies include effects on GFR whereas others used doubling of serum creatinine. Longitudinal data on estimated GFR were consistent with previous studies showing that ertugliflozin was associated with an initial reduction in GFR but over time a benefit on GFR versus placebo consistent with preservation of renal function with this drug was seen. There were some modest differences between the two doses of this drug but one must be cautious in overinterpreting such findings which warrant further careful post-hoc analysis albeit the ultimate significance of these findings may be difficult to evaluate. In terms of side effects there was as expected increase in genital infections in both males and females as well as an increased number of episodes of ketoacidosis although such events were rare. Other potential risks seen with other drugs of this class such as amputation, bone fracture and volume depletion were not observed. In summary ertugliflozin seems to have similar effects in terms of cardiovascular and renal protection to other agents in this class but as demonstrated previously with some of the other SGLT2 inhibitors no consistent benefit has been seen with respect to atherosclerotic events in this type 2 diabetic population with established cardiovascular disease. Thus, it is considered that the VERTIS study provides additional data to support the current EASD/ADA recommendations for the use of these agents in the type 2 diabetic population particularly in those with or at risk of cardiovascular and/or renal disease.