BACKGROUND The cardiovascular effect of liraglutide, a glucagon-like peptide 1 analogue, when added to standard care in patients with type 2 diabetes, remains unknown. METHODS In this double-blind trial, we randomly assigned patients with type 2 diabetes and high cardiovascular risk to receive liraglutide or placebo. The primary composite outcome in the time-to-event analysis was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The primary hypothesis was that liraglutide would be noninferior to placebo with regard to the primary outcome, with a margin of 1.30 for the upper boundary of the 95% confidence interval of the hazard ratio. No adjustments for multiplicity were performed for the prespecified exploratory outcomes. RESULTS A total of 9340 patients underwent randomization. The median follow-up was 3.8 years. The primary outcome occurred in significantly fewer patients in the liraglutide group (608 of 4668 patients [13.0%]) than in the placebo group (694 of 4672 [14.9%]) (hazard ratio, 0.87; 95% confidence interval [CI], 0.78 to 0.97; P<0.001 for noninferiority; P=0.01 for superiority). Fewer patients died from cardiovascular causes in the liraglutide group (219 patients [4.7%]) than in the placebo group (278 [6.0%]) (hazard ratio, 0.78; 95% CI, 0.66 to 0.93; P=0.007). The rate of death from any cause was lower in the liraglutide group (381 patients [8.2%]) than in the placebo group (447 [9.6%]) (hazard ratio, 0.85; 95% CI, 0.74 to 0.97; P =0.02). The rates of nonfatal myocardial infarction, nonfatal stroke, and hospitalization for heart failure were nonsignificantly lower in the liraglutide group than in the placebo group. The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was nonsignificantly lower in the liraglutide group than in the placebo group. CONCLUSIONS In the time-to-event analysis, the rate of the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke among patients with type 2 diabetes mellitus was lower with liraglutide than with placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048.)

In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semaglutide. (Funded by Novo Nordisk; SUSTAIN-6 ClinicalTrials.gov number, NCT01720446 .).

In patients who presented with an acute coronary syndrome and underwent percutaneous coronary intervention, major adverse cardiovascular events occurring during follow-up were equally attributable to recurrence at the site of culprit lesions and to nonculprit lesions. Although nonculprit lesions that were responsible for unanticipated events were frequently angiographically mild, most were thin-cap fibroatheromas or were characterized by a large plaque burden, a small luminal area, or some combination of these characteristics, as determined by gray-scale and radiofrequency intravascular ultrasonography. (Funded by Abbott Vascular and Volcano; ClinicalTrials.gov number, NCT00180466.).

Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .).

This prespecified secondary analysis shows that, when added to usual care, liraglutide resulted in lower rates of the development and progression of diabetic kidney disease than placebo. (Funded by Novo Nordisk and the National Institutes of Health; LEADER ClinicalTrials.gov number, NCT01179048 .).

BACKGROUND-Degludec is an ultralong-acting, once-daily basal insulin that is approved for use in adults, adolescents, and children with diabetes. Previous open-label studies have shown lower day-to-day variability in the glucose-lowering effect and lower rates of hypoglycemia among patients who received degludec than among those who received basal insulin glargine. However, data are lacking on the cardiovascular safety of degludec.

Peripheral arterial disease (PAD) is a chronic, lifestyle-limiting disease and is an independent predictor of cardiovascular and cerebrovascular ischemic events. Despite the recognition that PAD is associated with a marked increase in the risk of ischemic events, this particular manifestation of systemic atherosclerosis is largely underdiagnosed and undertreated. The risk of PAD is markedly increased among individuals with diabetes, and ischemic event rates are higher in diabetic individuals with PAD than in comparable non-diabetic populations. Consequently, early diagnosis and treatment of PAD in patients with diabetes is critically important in order to reduce the risk of cardiovascular events, minimize the risk of long-term disability, and improve quality of life. A diagnosis of PAD in patients with diabetes mandates a multi-faceted treatment approach, involving aggressive risk-factor modification, antiplatelet therapy, and revascularization procedures. The American Diabetes Association recently issued a consensus statement on the epidemiology, pathophysiology, diagnosis, and management of PAD in patients with diabetes. This article will review the clinical implications of the consensus statement and highlight the treatment options available in order to help prevent future ischemic events in diabetic individuals with PAD.

Background-Hyperglycemia on admission is associated with an increased mortality rate in patients with acute myocardial infarction. Whether metrics that incorporate multiple glucose assessments during acute myocardial infarction hospitalization are better predictors of mortality than admission glucose alone is not well defined. Methods and Results-We evaluated 16 871 acute myocardial infarction patients hospitalized from January 2000 to December 2005. Using logistic regression models and C indexes, 3 metrics of glucose control (mean glucose, time-averaged glucose, hyperglycemic index), each evaluated over 3 time windows (first 24 hours, 48 hours, entire hospitalization), were compared with admission glucose for their ability to discriminate hospitalization survivors from nonsurvivors. Models were then used to evaluate the relationship between mean glucose and in-hospital mortality. All average glucose metrics performed better than admission glucose. The ability of models to predict mortality improved as the time window increased (C indexes for admission, mean 24 hours, 48 hours, and hospitalization glucose were 0.62, 0.64, 0.66, 0.70; PϽ0.0001). Statistically significant but small differences in C indexes of mean glucose, time-averaged glucose, and hyperglycemic index were seen. Mortality rates increased with each 10-mg/dL rise in mean glucose Ն120 mg/dL (odds ratio, 1.8; Pϭ0.003 for glucose 120 to Ͻ130 mg/dL) and with incremental decline Ͻ70 mg/dL (odds ratio, 6.4; Pϭ0.01 versus glucose 100 to Ͻ110 mg/dL). The slope of these relationships was steeper in patients without diabetes. Conclusions-Measures of persistent hyperglycemia during acute myocardial infarction are better predictors of mortality than admission glucose. Mean hospitalization glucose appears to be the most practical metric of hyperglycemiaassociated risk. A J-shaped relationship exists between average glucose and mortality, with both persistent hyperglycemia and hypoglycemia associated with adverse prognosis.