Oral hypoglycemic agents and the heart failure conundrum: Lessons from and for outcome trials

• Glucose lowering by antiglycemic drugs in early stages of T2D might be beneficial on CVD.
• Effect of antidiabetic drugs on CVD and heart failure is rather class-dependent than due to the glucose lowering effect.
• Some classes of antiglycemic drugs are suspected to cause heart failure but data are not clear.
• Rate of MACE is not increased with the DPPIV inhibitors, underscoring the CV safety of these novel antidiabetic drugs.
• Results of TECOS indicate that increased HF hospitalization seen with saxagliptin is not a class effect of DPPIV inhibitors.

AimType 2 diabetes is not only an independent risk factor for cardiovascular (CV) disease but is also associated with a greater incidence of heart failure (HF). The aim of this review is to examine the effects of oral antidiabetic drugs on CV disease and HF.Data synthesisTrials of anti-diabetic agents are now designed to assess CV safety, but frequently HF is not included as a primary endpoint. However, HF in patients with diabetes is more frequent than other CV events and seems to be underestimated. A burning question is therefore if the most used trial design to monitor CV safety, i.e. non-inferiority, allows clinical translation of trial findings. Available data further suggest that the CV effects of anti-diabetic drugs may be rather class-specific and are only partly due to their glucose-lowering actions. Metformin, recommended as first line in most guidelines, shows positive CV effects while other classes like thiazolidinediones may precipitate HF. Experimental results on the relatively novel dipeptidyl peptidase IV (DPP IV) inhibitors imply CV protective effects, but the non-inferiority trials published to date show an overall neutral CV outcome and a potential increase in HF by saxagliptin. However, results on sitagliptin of the recently released TECOS indicate that HF is not a class-dependent effect of DPP IV inhibitors.ConclusionFurther basic research and long-term outcome studies to clarify the effects of antidiabetic agents on CV and HF are required so that we can select the optimal antidiabetic therapy for our patients.