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.

Objective-Serum levels of fibroblast growth factor-21 (FGF21), a metabolic hormone, have been shown to be elevated in subjects with adverse lipid profiles, obesity, metabolic syndrome, impaired glucose tolerance, type 2 diabetes mellitus, and hypertension. Recently, elevated serum FGF21 levels have also been reported in subjects with coronary heart disease or carotid artery plaques. However, whether serum FGF21 is independently associated with atherosclerotic diseases remains unclear. In this study, we examined the relationship between serum FGF21 levels and carotid intima-media thickness (IMT) in a large cohort of Southern Chinese subjects. Approach and Results-The cohort consisted of 670 subjects who underwent carotid IMT measurement. Serum FGF21 levels were measured with an ELISA kit. Serum FGF21 levels positively correlated with carotid IMT in women (r=0.32; P<0.001), but not in men (r=0.06; P=0.305). On multiple linear regression analysis, elevated serum FGF21 level in women was an independent risk factor for increased carotid IMT (P=0.039), together with age (P<0.001) and hypertension (P=0.011), in a model comprising also waist circumference, smoking history, serum creatinine, high sensitive C-reactive protein, dysglycemia, and dyslipidemia (adjusted R 2 =35.8%; P<0.001). Elevated serum FGF21 levels were also a significant independent risk factor of carotid IMT on multiple stepwise regression analysis (P=0.01). with type 2 DM. 12,13 However, whether serum FGF21 is independently associated with atherosclerotic diseases remains unclear. To evaluate the relationship between serum FGF21 levels and atherosclerosis, we examined in 670 Southern Chinese subjects with no overt macrovascular disease the association between serum FGF21 levels and carotid intima-media thickness (IMT), a well-established marker of atherosclerosis. Conclusions-The14 Established cardiovascular risk factors and high sensitive C-reactive protein (CRP) were also measured to determine whether FGF21 is an independent risk factor for increased carotid IMT. Materials and MethodsMaterials and Methods are available in the online-only Supplement. ResultsThe demographic and biochemical characteristics of the subjects are summarized in Table 1. Of the 502 subjects recruited from the third assessment of the Hong Kong Cardiovascular Risk Factor Prevalence Study, 262, 128, and 112 had normal glucose tolerance, impaired glucose tolerance (IGT)/impaired fasting glucose (IFG) and DM, respectively. In all, 176 (26.3%) and 76 (11.3%) of the 670 subjects were on antidiabetic and lipid-lowering medications, respectively. The former group comprised 109 metformin-treated subjects. For the use of peroxisome proliferator-activated receptors agonists, 20 subjects of the entire cohort were treated with fibrates and none of them was on thiazolidinediones. For these treatment modalities, there were no between-group differences in serum FGF21 levels based on analysis in which subjects were stratified according to the use of medication.Among subjects with different gl...

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