Sécurité cardiovasculaire des incrétines et des inhibiteurs des co-transporteurs sodium-glucose de type 2 (SGLT2). Revue

Today, FDA requires that cardiovascular safety studies should be conducted for each new antidiabetic drug according to strict predefined judgment criteria. For the class of incretins, DPP4 inhibitors (DPP4-i) and GLP1 receptor agonists (GLP1-RA), we already have the results of four studies: SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin) TECOS (sitagliptin) and ELIXA (lixisenatide), more than 40,000 type 2 diabetics, and for the primary endpoint (MACE) the data are fully reassuring (strict noninferiority vs. placebo). Nevertheless in the SAVOR-TIMI 53 study an excess risk, statistically significant, of hospitalization forheart failure has been clearly identified, not found in the three other studies with incretins. The question is: unfortunate statistical chance in SAVOR-TIMI 53, or specific effect due to the molecule (saxagliptin)? But certainly nota class effect. The only available study on the new class, sodium-glucose cotransporter 2 inhibitors (SGLT2-i), EMPA-REG (with empagliflozin) showed superiority vs. placebo, for the primary endpoint (MACE 3-points), -38%, largely driven by a lower cardiovascular mortality and hospitalization for heart failure. Two very early findings, rather in favor of effects independent of glycemic benefit, rather due to blood pressure, renal, vascular, volemic or diuretic effects, specific to these class of drugs. Over 94,000 other patients are being studied with other GLP1-RA (liraglutide, once-a-day, and four once-a-week, exenatide OW, dulaglutide, albiglutide, and semaglutide), and three SGLT2-i (canagliflozin, dapagliflozin, and ertugliflozin). Today we can retain a neutral (incretins) or cardiovascular benefits (SGLT2-i) of the new antidiabetic drugs. However through this data as other works, heart failure appears to be an important concern for type 2 diabetes people.