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.

These results suggest that there are substantial variations in glycaemic control among people with Type 1 diabetes between the data sources and that there is room for improvement in all populations, especially in young adults.

We have found that the addition of vildagliptin to metformin for a period of six months decreased hsCRP, improved glycemic control and β-cell function but had no effect on AS in drug-naive patients with T2DM.

Objective To identify differences in the post-exercise phosphocreatine (PCr) recovery, an index of mitochondrial function, in diabetic patients with and without lower extremity complications. Research Methods and Design We enrolled healthy control subjects and three groups of T2DM patients: patients without complications, with peripheral neuropathy and both peripheral neuropathy and peripheral arterial disease. We employed Magnetic Resonance Spectroscopic (MRS) measurements to perform continuous measurements of phosphorous metabolites (PCr and Pi) during a 3-minute graded exercise at the level of the posterior calf muscles (gastrocnemius and soleus muscles). Micro- and macrovascular reactivity measurements were also performed. Results The resting Pi/PCr ratio and PCr at baseline and the maximum reached during exercise was similar in all groups. The post-exercise time required for recovery of Pi/PCr ratio and PCr levels to resting levels, an assessment of mitochondrial oxidative phosphorylation, was significantly higher in the diabetic patients with neuropathy and those with both neuropathy and PAD (p <0.01 for both measurements). These two groups had also higher levels of TNFα, (p<0.01) and G-CSF (p <0.05). Multiple regression analysis showed that only G-CSF, OPG and TNFα were significant contributing factors in the variation of the Pi/PCr ratio recovery time. No associations were observed between micro- and macrovascular reactivity measurements and Pi/Pcr ration or Pcr recovery time. Conclusions Mitochondrial oxidative phosphorylation is impaired only in T2DM patients with neuropathy whether PAD is present or not and is associated with the increased proinflammatory state that was observed in these groups.