Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome

Abstract

BACKGROUND: Cardiovascular morbidity and mortality are higher among patients with type 2 diabetes, particularly those with concomitant cardiovascular diseases, than in most other populations. We assessed the effects of lixisenatide, a glucagon-like peptide 1-receptor agonist, on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event. METHODS: We randomly assigned patients with type 2 diabetes who had had a myocardial infarction or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined standards of care. The trial was designed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo, as defined by an upper boundary of the 95% confidence interval for the hazard ratio of less than 1.3 and 1.0, respectively, for the primary composite end point of cardiovascular death, myocardial infarction, stroke, or hospitalization for unstable angina. RESULTS: The 6068 patients who underwent randomization were followed for a median of 25 months. A primary end-point event occurred in 406 patients (13.4%) in the lixisenatide group and in 399 (13.2%) in the placebo group (hazard ratio, 1.02; 95% confidence interval [CI], 0.89 to 1.17), which showed the noninferiority of lixisenatide to placebo (P<0.001) but did not show superiority (P=0.81). There were no significant between-group differences in the rate of hospitalization for heart failure (hazard ratio in the lixisenatide group, 0.96; 95% CI, 0.75 to 1.23) or the rate of death (hazard ratio, 0.94; 95% CI, 0.78 to 1.13). Lixisenatide was not associated with a higher rate of serious adverse events or severe hypoglycemia, pancreatitis, pancreatic neoplasms, or allergic reactions than was placebo. CONCLUSIONS: In patients with type 2 diabetes and a recent acute coronary syndrome, the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events. (Funded by Sanofi; ELIXA ClinicalTrials.gov number, NCT01147250.). Jean-Claude (2015). Lixisenatide in patients with type 2 diabetes and acute coronary syndrome.

Prevalent and Incident Heart Failure in Cardiovascular Outcome Trials of Patients With Type 2 Diabetes

“…Aside from BARI 2D, incident HF was either not directly adjudicated or the adjudication status was unclear. Additionally, these 5 other studies included non-specific definitions of new onset HF with 4 studies providing data for hospitalization for HF among patients without prior history of HF (28,29,31,32). The remaining study (EMPA-REG OUTCOME) reported data on introduction of loop diuretics during follow-up (24).…”

Contemporary risk estimates of three HbA1cvariables in relation to heart failure following diagnosis of type 2 diabetes

“…The clinical trials of incretin-based therapies have not so far shown any preventive effect on CVD but were generally designed to show non-inferiority and may have preventive effects over longer time periods. [22][23][24] Studying various HbA 1c metrics offers clinicians compound perspectives on this biomarker with potentially differing purposes and utilities. The baseline HbA 1c provides the clinician with information on whether the glycaemic control at diagnosis already has a predictive value on complications at later stages.…”

Lower Cardiovascular Risk with Diabetic Drugs: A Paradigm Shift from Glucocentricity to Cardio Protectiveness

“…After a median follow-up of 25 months, there was no difference in the primary composite endpoint of cardiovascular death, non-fatal MI, non-fatal stroke, or hospitalization for unstable angina between groups (13.4 vs 13.2%, HR 1.02, 95% CI 0.89-1.17, p=0.81 for superiority, p<0.001 for non-inferiority), and no difference in heart failure hospitalizations (4.0 vs 4.2%, HR 0.96, 95% CI 0.75-1.23) [47]. n the Liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results (LEADER) trial, which randomized 9340 T2DM patients with high cardiovascular risk, liraglutide reduced the primary composite endpoint of cardiovascular death, non-fatal MI or non-fatal stroke compared to placebo after a median follow-up of 3.8 years (13 vs 14.9%, HR 0.8, 95% CI 0.78-0.97, p<0.001 for noninferiority; p=0.01 for superiority) [48].…”