Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor 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. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Adipokines and metabolic parameters in patients with type 2 diabetes mellitus in combination with gout

Aim. To study the impact of type 2 diabetes and its combination with gout on the level of adipokines, hormonal and metabolic parameters.Materials and methods. The study included 18 men with type 2 diabetes with a mean age 57,83 ± 1,67 years, and 21 subjects with a combination of type 2 diabetes and gout, whose average age was 57,57 ± 1,44 years. The controls were 40 healthy men: 20 subjects with an average age of 21,03 ± 0,15 years and 20 men with average age 51,31 ± 1,34 years. All patients had anthropometric measurements, evaluation of parameters of lipid and carbohydrate metabolism, uric acid, levels of adiponectin, leptin and resistin.Results. Patients of both groups had elevated concentrations of leptin, resistin and reduced level of adiponectin. Men with type 2 diabetes, and its combination with gout had increased levels of total cholesterol, triglycerides, glucose and insulin.Conclusion. In patients with type 2 diabetes, and its combination with gout are characterized by hyperleptinemia, hypererresistinemia, hypooadiponectinemia. Insulin resistance with compensatory hyperinsulinemia and atherogenic dyslipidemia was found in all patient groups

Basal insulin therapy in patients with type 2 diabetes mellitus and poor control of glycemia by oral hypoglycemic agents: results of direct comparative study of insulin analogs Lantus and Levemir

Aim. To compare efficiency of two regimes of basal therapy with human insulin analogs glargin (Lantus) once daily and detemir (Levemir) twicedaily based on their hypoglycemic action (HbA1