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.

The Current Role of Glucose Control Medications in Primary and Secondary Prevention for Cardiovascular Disease

“…10 Recent trials using newer therapies like dipeptidyl peptidase-4 demonstrated non inferiority (safety) in cardiovascular outcomes among patients with T2DM and existing CVD or at higher risk of events. [11][12][13][14] Recently, for example, the use of sitagliptin in more than 7.000 patients -in the TECOS trial -was not associated with an increased risk of heart failure or related adverse outcomes after Sitagliptin therapy.11 There was, however, an increase in the rate of hospitalization for HF with the use of saxagliptin (SAVOR-TIMI 53) trial. 14 The glucagon-like peptide 1 analogue is another type of antidiabetic drugs that had controversial results in outcomes among diabetic patients in recent trials.…”

GLP-1 receptor agonists and heart failure in diabetes

“…In fact, the lack of any significant difference in the risk of hospitalizations for HF between those treated with a GLP-1RA or a placebo reported with liraglutide in LEADER [24] was confirmed with lixisenatide in the Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial [47] and with semaglutide in the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN-6; Table 4) [48]. Unfortunately, no measurements of pro-BNP levels were available in the LEADER trial [24], and this key information was also missing in the ELIXA [47] and SUSTAIN-6 [48].…”

“…Unfortunately, no measurements of pro-BNP levels were available in the LEADER trial [24], and this key information was also missing in the ELIXA [47] and SUSTAIN-6 [48]. However, such measurements were included in two trials of DPP-4 inhibitors: the EXAMINE with alogliptin [49]; and SAVOR -TIMI 53 with saxagliptin [50].…”

A new era in the management of type 2 diabetes: Is cardioprotection at long last a reality?

“…In 2015, a third trial testing a DPP-4 inhibitor, the trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS) [9], found that the addition of sitagliptin to usual care among patients with glycemic equipoise does not affect rates of major atherosclerotic cardiovascular events, including changes in rates of hospitalization for heart failure [9]. In 2015, the Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial [10] reported that another incretin-based therapy, a GLP-1 receptor analogue, did not significantly affect the rate of major cardiovascular events or other serious adverse events in T2DM with a recent acute coronary syndrome.…”