Interpretation of cardiovascular outcome trials in type 2 diabetes needs a multiaxial approach

Figure 1 Anticipated ending of outcome trials in type 2 diabetes and their primary outcomes and patient/event numbers involving di-peptidyl peptidase-4 inhibitors, glucagon-like protein-1 receptor analogues and sodium glucose co-transporter-2 inhibitors. Superscript note indicate study drug(s) in testing. All trials are placebo controlled except CAROLINA^® that compared vs the sulfonylurea glimepiride. ¹Saxagliptin, Astra Zeneca; ²Alogliptin, Takeda; ³Sitagliptin, Merck; ⁴Linagliptin, Boehringer Ingelheim/Eli Lilly; ⁵Lixisenatide, Sanofi Aventis; ⁶Liraglutide, Novo Nordisk; ⁷Semaglutide, Novo Nordisk; ⁸Exenatide, Astra Zeneca; ⁹Dulaglutide, Eli Lilly; ¹⁰Empagliflozin, Boehringer Ingelheim/Eli Lilly; ¹¹Canagliflozin, J and J; ¹²Dapagliflozin, Astra Zeneca; ¹³Omarigliptin (once weekly tablet), Merck; ¹⁴ITCA 650 [once/twice yearly exenatide via subcutaneous mini-pump (Duros device)], Intarcia Therapeutics. DPP-4: Di-peptidyl peptidase-4; GLP-1: Glucagon-like protein-1; SGLT-2: Sodium glucose co-transporter-2; MACE3: Composite endpoint of cardiovascular death, non-fatal myocardial infarction and non-fatal stroke; MACE4: MACE3 plus hospitalized unstable angina pectoris; MACE5: MACE4 plus hospitalized congestive heart failure.

Figure 2 Selected outcome trials in type 2 diabetes with a focus on di-peptidyl peptidase-4 inhibitor studies, and their results, in the context of the duration of intervention and the study population’s diabetes duration and baseline cardiovascular risk. CV: Cardiovascular; UKPDS: United Kingdom Prospective Diabetes Study; VADT: Veterans affairs diabetes trial.