Effect of sitagliptin on cardiovascular outcomes in type 2 diabetes

BACKGROUND: Data are lacking on the long-term effect on cardiovascular events of adding sitagliptin, a dipeptidyl peptidase 4 inhibitor, to usual care in patients with type 2 diabetes and cardiovascular disease. METHODS: In this randomized, double-blind study, we assigned 14,671 patients to add either sitagliptin or placebo to their existing therapy. Open-label use of antihyperglycemic therapy was encouraged as required, aimed at reaching individually appropriate glycemic targets in all patients. To determine whether sitagliptin was noninferior to placebo, we used a relative risk of 1.3 as the marginal upper boundary. The primary cardiovascular outcome was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. RESULTS: During a median follow-up of 3.0 years, there was a small difference in glycated hemoglobin levels (least-squares mean difference for sitagliptin vs. placebo, -0.29 percentage points; 95% confidence interval [CI], -0.32 to -0.27). Overall, the primary outcome occurred in 839 patients in the sitagliptin group (11.4%; 4.06 per 100 person-years) and 851 patients in the placebo group (11.6%; 4.17 per 100 person-years). Sitagliptin was noninferior to placebo for the primary composite cardiovascular outcome (hazard ratio, 0.98; 95% CI, 0.88 to 1.09; P<0.001). Rates of hospitalization for heart failure did not differ between the two groups (hazard ratio, 1.00; 95% CI, 0.83 to 1.20; P = 0.98). There were no significant between-group differences in rates of acute pancreatitis (P = 0.07) or pancreatic cancer (P = 0.32). CONCLUSIONS: Among patients with type 2 diabetes and established cardiovascular disease, adding sitagliptin to usual care did not appear to increase the risk of major adverse cardiovascular events, hospitalization for heart failure, or other adverse events

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: 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 .)

Muscle strength differ between patients with diabetes and controls following heart surgery

The aim of our study was to analyze muscle strength in patients with recent surgical treatment for ischemic and combined ischemic- valvular heart disease, based on existence of diabetes mellitus. Connections existing between muscle strength and patient characteristics or conventional diagnostic tests were analyzed as well. Study prospectively included consecutive patients scheduled for cardiovascular rehabilitation 0–3 months after heart surgery. Diagnostics covered drug utilization, anthropometrics, demographics, echocardiography, conventional laboratory, echocardiography, bioelectrical impedance analysis (BIA), and hand grip test (HGT). HGT was analyzed for dominant hand. Patients with diabetes had significantly weaker muscle strength on HGT than controls ; 29.4 ± 12.2 kg vs. 38.2 ± 14.7 kg (p = 0.029), respectively. ROC analysis for HGT and existence of diabetes mellitus were significant ; ≤ 40 kg had sensitivity of 89.7% (95%CI: 72.6–97.8), specificity 43.7% (31.9– 56.0) ; AUC 0.669 (0.568–0.760) ; p = 0.002. HGT significantly correlated with hematocrit (Rho CC = 0.247 ; p = 0.013), whilst other laboratory or echocardiographic parameters were insignificant (all p > 0.05). HGT also correlated with body weight (Rho CC = 0.510 ; p < 0.001) ; height (Rho CC = 0.632 ; p < 0.001) ; waist circumference (Rho CC = 0.388 ; p < 0.001) ; waist-to-hip ratio (Rho CC = 0.274 ; p = 0.006) and BIA (Rho CC = − 0.412 ; p < 0.001). In postoperative recovery of patients with diabetes, muscle strength assessed by HGT is decreased and in relation with nutritional status. Clinically resourceful connections of HGT were also found to hematocrit and utilization of loop diuretics