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.

Hypothyroidism results in disturbances of metabolism influencing many regulatory systems and active molecules as adipocytokines. Objective of the study was to investigate leptin and adiponectin in patients with visceral obesity and hypothyroidism in relation to metabolic status, insulin resistance and systemic inflammation. A total of 118 patients (59 hypothyroid and 59 euthyroid) were enrolled divided into four age-matched groups according to body wеight (BMI) and thyroid function. Laboratory panel includes TSH, FT4, FT3 (CMIA), adiponectin and leptin (ELISA), IL- 6 (ECLIA), CRP, insulin, glucose, apolipoprotein B and lipoprotein (a) - Lp(a). Hypothyroid patients revealed significant positive correlations of TSH, adiponectin and Lp(a). Their medians of 10.4 mU/l, 12.5 µg/ml and 116.3 mg/l respectively were significantly higher than in euthyroid patients- 1.5 mU/l, 6.26 µg/ml and 32.0 mU/l (p < 0.0001). Leptin in both obese groups was significantly higher than in patients with normal weight. Leptin in hypothyroid patients was lower but not significant to euthyroid ones (9.7 ng/ml vs 13.4 ng/ml respectively, p = 0.16), correlated negatively to TSH and positively to CRP, IL-6, ApoB, Lp(a) and BMI. HOMA-IR and serum insulin at 120 min in OGTT were significantly higher in hypothyroid than in euthyroid patients independent of BMI (p < 0.001). Adiponectin, insulin resistance and chronic inflammation indices in hypothyroid patients correlated positively to TSH, BMI and atherogenic lipoproteins subclasses ApoB/Lp(a). Increased adiponectin in thyroid deficiency could be due to secondary resistance of adiponectin receptors or appeared as a compensatory pathogenetic factor in hypothyroidism.

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Introduction: Hypothyroidism, metabolic syndrome and central obesity are common diseases known as the risk factors for atherosclerotic cardiovascular disease. The coexistence of thyroid dysfunction in obese patients might substantially increase the cardiovascular risk. The objective of the study was to evaluate the effect of hypothyroidism on the main cardiovascular risk factors in patients with obesity and cardiovascular syndrome. Material and methods: In a cross-sectional clinical study we examined 202 patients with central obesity and metabolic syndrome (160 women, 42 men, aging 43 ± 13 yrs) with BMI ≥ 30 kg/m 2 divided in two groups-101 patients with subclinical or overt hypothyroidism (gr. A-hypot) and 101 eythyroid patients (gr B-eut), diagnosed by TSH, FT4,TPO-Ab. Laboratory assessment included: total cholesterol (TChol), HDL,LDL, triglycerides (3-glyc), serum glucose, standard oral glucose tolerance test (OGTT) and insulin resistance by Homeostasis Model Assessment of Insiline Resistance (HOMA-IR). Serum leptin and C-reactive proteins were estimated in 20 patients of each patients group and in a control group of 20 healthy persons with BMI <25 kg/m 2. The supplementation Levothyroxine therapy was carried out of patients with overt and subclinial hypothyroidism. Results: Both compared groups showed similar BMI (mean 37 kg/m 2) and HOMA-IR value 3.1 and 3.15, respectively Mean TSH value was found 4-fold higher in gr. A than in gr. B. which significantly correlated with TChol, 3-glyc, CRP and serum leptin The prevalence of arterial hypertension (AH), diabetes type2 or impaired glucose tolerance (IGT) in gr A was 86% and 67% vs. 80% and 70% in gr B, respectively. Significant correlations were established between TSH, TChol, atherogenic lipoproteins, 3-glyc. in patients gr. A but not in gr B. The same parameters decreased significantly after adequate levothyroxin supplementation. The significant positive nonparametric correlations were found also between BMI, TSH, leptin and CRP (p<0.05). Conclusion: Our data demonstrate that hypothyroidism significantly aggravates the lipid metabolisms in patients with obesity or MetS. These disturbances co-existing with higher prevalence of arterial hypertension, DM-T2 or IGT determine the substantially increased cardiovascular risk which correlated with increased insulin resistance, higher levels of leptin and CRP as a marker of chronic inflammation. Consequently clinicians shouid be particularly alert in the possibility of thyroid disfunction in obese patients.