The following are key points to remember from this European Society of Cardiology position paper on non-insulin antidiabetic pharmacotherapy in patients with established cardiovascular disease (CVD):

1. In patients with type 2 diabetes mellitus (T2DM) and CVD, antidiabetic pharmacotherapy should be chosen based on beneficial effects on CV events in phase III and post-marketing trials.
2. The European Medicines Agency (EMA) has recently stated that improvement of glycemic control and reduction of CV morbidity and mortality should be major goals in the treatment of T2DM.
3. While sulfonylureas are widely used, no data about their safety in patients with CVD are available. In addition, they promote weight gain, and cause hypoglycemia, mainly with first-generation sulfonylureas and immediate-release formulations with the latter two adverse effects being associated with increased CV risk.
4. So far, the sodium glucose cotransporter 2 (SGLT2) inhibitors empagliflozin and canagliflozin, and the glucagon-like peptide-1 (GLP-1) receptor agonist (RA) liraglutide and semaglutide, reduced CV events in adequately powered studies. However, for canagliflozin, the net benefit is restricted by an increased rate of amputations. For semaglutide, EMA approval is pending.
5. Currently, the SGLT2 inhibitor empagliflozin, and the GLP-1 RA liraglutide, may be considered preferred treatment choices.
6. The 2016 European Guidelines on CVD prevention recommended that in patients with T2DM and CVD, an SGLT2 inhibitor should be considered early in the therapeutic process to reduce CV and total mortality (Class IIa recommendation).
7. While the power of outcome data for metformin is limited, economic reasons, ample clinical experience, and safe use in combination with other antidiabetic therapies are reasons to continue to use this drug as first choice.
8. When these preferred treatments are not sufficient to achieve therapeutic goals or are contraindicated, the thiazolidinedione pioglitazone, the GLP-1 RA exenatide, and dipeptidyl peptidase 4 (DPP-4) inhibitors may be further choices due to their neutral or potentially beneficial effects on cardiovascular events in adequately powered, contemporary trials.
9. Contemporary trials have shown a neutral effect of the DPP-4 inhibitors saxagliptin and sitagliptin on the primary CV endpoint in patients with stable CVD or at risk for CVD. There is no evidence supporting a combination of DPP-4 inhibitors with a GLP-1 RA.
10. Future clinical trials should pursue the possible benefit of antidiabetic pharmacotherapy on hard CV endpoints in various specified types of CVD.

Keywords: Amputation, Cardiovascular Diseases, Diabetes Mellitus, Type 2, Dipeptidyl-Peptidase IV Inhibitors, Drug Therapy, Glucagon-Like Peptide 1, Hypoglycemia, Hypoglycemic Agents, Insulin, Metformin, Metabolic Syndrome, Peptides, Primary Prevention, Sodium-Glucose Transporter 2, Thiazolidinediones, Weight Gain

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