Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

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Our data confirm in PBC patients that serum bound leptin levels are increased and clearly show a parallel decrease in serum ghrelin concentrations acting as a physiological counterpart to leptin. Furthermore, we suggest that these changes are linked to the insulin resistance observed in our patients.

SUMMARY. To determine the mechanical factors affecting regional segmental motion after acute coronary occlusion, we studied seven conscious dogs, instrumented with sonomicrometers. Loading conditions were changed by the withdrawal of 500 ml of blood and the transfusion of 800 ml of blood. To express segmental motion, percent systolic shortening, percent systolic elongation, and early diastolic shortening were calculated. Blood withdrawal decreased left ventricular preload, increased percent systolic elongation (from 6.9 ± 3.1% to 9.9 ± 3.5%) and early diastolic shortening (12.9 ± 5.3% to 16.6 ± 5.3%), and decreased percent systolic shortening. Blood transfusion increased left ventricular preload, decreased percent systolic elongation (to 5.2 ± 1.8%) and early diastolic shortening (8.8 ± 2.9%), and increased percent systolic shortening. Manipulation of loading did not change regional myocardial blood flow. In acutely ischemic myocardium, the tension-length loop showed an exponential upstroke during isovolumic systole and a nearly superimposed exponential downsrroke during the isovolumic relaxation phase after systole, compatible with essentially passive movement as seen with an elastic material. The changes in loading conditions affected the tension-length curve to a very minor extent. The uniformity of the curve and its exponential shape explain the load-dependency of systolic bulding and segmental motion. It is concluded that systolic bulging depends on the change in the preload tension due to the compliant portion of tension-length curve, and that shortening of ischemic myocardium during the isovolumic relaxation phase is a completely passive phenomenon. (Circ Res 58: 209-217, 1986)