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

Chronic Diabetic Complications: Current Challenges and Opportunities

The Special Issue, “Chronic Diabetic Complications: Current Challenges and Opportunities”, is rich in scientific content, covering a wide field of diabetic complications via both original studies and reviews [...

The Cost of Managing Type 2 Diabetes Mellitus in Greece: A Retrospective Analysis of 10-Year Patient Level Data “The HERCULES Study”

Objective. This study aimed to estimate the mean annual cost of treating type 2 diabetes mellitus patients (T2DM) including complications and comorbidities in Greece. Design. A noninterventional retrospective study was based on patient level data analysis (bottom-up approach) from medical records, with at least 10-year-follow-up data. Results. The total annual cost per patient for managing diabetes in Greece was estimated at € 7,111 and was, statistically significantly, higher for patients with inadequate glycemic control (Hba1c>7%) versus patients with adequate control (Hba1c=7%) (€ 7,783 versus € 6,366, resp.;   P=0.017). This was mainly attributed to difference in CV hospitalizations between groups 14/111 versus 4/100, respectively, OR=3.46 (95% CI: 1.10–10.9) for inadequately controlled patients. The largest component of cost was management of comorbidities, accounting for 48% of costs, and pharmaceutical treatment at 35.9% while only 14.9% was attributed to diabetes treatment per se. Obese men and patients with poor education are the groups with higher treatment costs. Conclusions. This is the first study to capture all cost components and the real burden of diabetes in Greece. Comorbidities were found to account for almost half of total cost, significantly higher in nonoptimally controlled diabetes patients

Spontaneous peritonitis caused by Leminorella grimontii

A case of spontaneous peritonitis caused by Leminorella grimontii in a 63-year-old man with cirrhosis is reported. To our knowledge, L. grimontii has never been reported as a cause of spontaneous bacterial peritonitis. The patient responded to antimicrobial therapy. Clinical and therapeutic implications are discussed. (c) 2006 Elsevier Inc. All rights reserved

B-cell chronic lymphocytic leukemia risk in association with serum leptin and adiponectin: a case-control study in Greece

Aim Leptin and adiponectin are two well-studied adipokines in relation to malignancies. In this study, we examined the association between leptin/adiponectin and risk of B-cell chronic lymphocytic leukemia (B-CLL), as well as the relationships between adipokines and several established prognostic factors of B-CLL. Methods Ninety-five patients with incident B-CLL and 95 hospital controls matched on age and gender were studied between 2001 and 2007, and blood samples were collected. Leptin, total and high molecular weight adiponectin, and prognostic markers of B-CLL were determined. Results Cases had a higher body mass index (BMI) than controls (p = 0.01) and lower levels of leptin (p < 0.01). Significantly more cases than controls presented a family history of lymphohematopoietic cancer (LHC) (p = 0.01). Higher serum leptin levels were associated with lower risk of B-CLL adjusting for age, gender, family history of LHC, BMI and serum adiponectin; the multivariate odds ratio comparing highest to lowest tertile was 0.05 (95% CI 0.01-0.29, p trend < 0.001); Adiponectin was not significantly different between cases and controls. Conclusion Leptin was found to be inversely associated with risk of CLL but in contrast to prior studies of CLL and hematologic malignancies, this study found no significant association between CLL and adiponectin

Hypertriglyceridemia and Other Risk Factors of Chronic Kidney Disease in Type 2 Diabetes: A Hospital-Based Clinic Population in Greece

Aims/Introduction: Several reports indicate an increasing prevalence of chronic kidney disease (CKD) in type 2 diabetes mellitus (T2DM). Hyperglycemia and hypertension are the main risk factors for CKD development and progression. However, despite the achievement of recommended targets for blood glucose and blood pressure (BP), the residual risk of diabetic chronic kidney disease (DCKD) remains relatively high. The aim of this study is to examine dyslipidemia and other major risk factors to provide support for the prevention and treatment of DCKD. Materials and Methods: Participants are from the Redit-2-Diag study that examines 1759 subjects within a period of 6 months. DCKD severity is staged according to KDIGO criteria. Results: An increase in hemoglobin A1c (1 unit) and systolic blood pressure (1 mm Hg) increases the probability of being classified into a higher CKD stage by 14% and 26%, respectively. Moreover, an increase of triglycerides by 88.5 mg/dL increases the risk of classification to a worse CKD stage by 24%. Conclusions: Elevated triglycerides, systolic blood pressure, and poor glycemic control increase the risk of CKD in T2DM and should be addressed in the treatment strategies