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.

Harmony Outcomes: A randomized, double-blind, placebo-controlled trial of the effect of albiglutide on major cardiovascular events in patients with type 2 diabetes mellitus-Rationale, design, and baseline characteristics.

Background: Albiglutide is a long-acting glucagon-like peptide-1 receptor agonist that improves glycemic control in patients with type 2 diabetes mellitus (T2DM). Harmony Outcomes is a randomized, double-blind, placebo-controlled trial of the effect of albiglutide on major adverse cardiovascular (CV) events in patients with T2DM and established CV disease.

Methods: The trial was designed to recruit 9,400 patients aged ≥40 years with T2DM, prior atherosclerotic CV disease, and suboptimal glycemic control.

Cancer and bone fractures in observational follow-up of the RECORD study.

Aims: The RECORD study evaluated the effects of rosiglitazone on cardiovascular outcomes. A 4-year observational follow-up was added to the study to monitor the occurrence of cancer and bone fractures. We present the cancer and bone fracture data aggregated across the main study and its observational follow-up.

Lipid effects of peroxisome proliferator-activated receptor-δ agonist GW501516 in subjects with low high-density lipoprotein cholesterol: characteristics of metabolic syndrome.

Objective: Peroxisome proliferator-activated receptor-δ-induced upregulation in skeletal muscle fatty acid oxidation would predict the modulation of lipid/lipoproteins.

Methods And Results: GW501516 (2.5, 5.

Incidence and prevalence of unrecognized myocardial infarction in people with diabetes: a substudy of the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) study.

Objective: To examine the prevalence and incidence of unrecognized myocardial infarction in a contemporary population with type 2 diabetes.

Research Design And Methods: We performed a retrospective analysis of the electrocardiograms (ECGs) recorded at baseline and after 2 years for the first 1,004 type 2 diabetic individuals to be randomized in the Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of Glycemia in Diabetes (RECORD) study.

Results: ECGs suitable for analysis were obtained from 669 participants.

Heart failure events with rosiglitazone in type 2 diabetes: data from the RECORD clinical trial.

Aims: Thiazolidinediones are insulin sensitizers, and are associated with fluid retention and increased risk of heart failure (HF) in people with type 2 diabetes. We assessed fatal and non-fatal HF events and their outcome, and identified HF predictors in the RECORD (Rosiglitazone Evaluated for Cardiac Outcomes and Regulation of glycaemia in Diabetes) trial population.

Methods And Results: In a multicentre, open-label study, we randomized 4447 people with type 2 diabetes on metformin or sulfonylurea monotherapy with a mean HbA(1c) of 7.

Effect of rosiglitazone, metformin, and glyburide on bone biomarkers in patients with type 2 diabetes.

Context: An increase in bone fractures has been observed in women taking thiazolidinediones.

Objective: The objective of the study was to examine whether changes in circulating bone biomarkers provide insight into the underlying mechanisms responsible for the increase in bone fractures in female participants randomized to rosiglitazone in A Diabetes Outcome Progression Trial (ADOPT).

Research Design And Methods: Paired stored baseline and 12-month serum samples were available from 1605 participants (689 women, 916 men) in ADOPT, a long-term clinical trial comparing the effects of rosiglitazone, glyburide, and metformin on glycemic control in patients with type 2 diabetes.

Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial.

Background: Rosiglitazone is an insulin sensitiser used in combination with metformin, a sulfonylurea, or both, for lowering blood glucose in people with type 2 diabetes. We assessed cardiovascular outcomes after addition of rosiglitazone to either metformin or sulfonylurea compared with the combination of the two over 5-7 years of follow-up. We also assessed comparative safety.

Effect of the addition of rosiglitazone to metformin or sulfonylureas versus metformin/sulfonylurea combination therapy on ambulatory blood pressure in people with type 2 diabetes: a randomized controlled trial (the RECORD study).

Background: Hypertension and type 2 diabetes are common co-morbidities. Preliminary studies suggest that thiazolidinediones reduce blood pressure (BP). We therefore used ambulatory BP to quantify BP lowering at 6-12 months with rosiglitazone used in combination with metformin or sulfonylureas compared to metformin and sulfonylureas in people with type 2 diabetes.

Rosiglitazone evaluated for cardiovascular outcomes--an interim analysis.

Background: A recent meta-analysis raised concern regarding an increased risk of myocardial infarction and death from cardiovascular causes associated with rosiglitazone treatment of type 2 diabetes.

Methods: We conducted an unplanned interim analysis of a randomized, multicenter, open-label, noninferiority trial involving 4447 patients with type 2 diabetes who had inadequate glycemic control while receiving metformin or sulfonylurea, in which 2220 patients were assigned to receive add-on rosiglitazone (rosiglitazone group), and 2227 to receive a combination of metformin plus sulfonylurea (control group). The primary end point was hospitalization or death from cardiovascular causes.

A one-year study comparing the efficacy and safety of rosiglitazone and glibenclamide in the treatment of type 2 diabetes.

Background And Aim: This study was designed to compare the efficacy of rosiglitazone and glibenclamide in individuals with type 2 diabetes over a 12-month period.

Methods And Results: A total of 598 patients were randomized to double-blind treatment for 52 weeks with rosiglitazone 4 mg/d (n=200), rosiglitazone 8 mg/d (n=191) or glibenclamide (n=207; dose adjusted up to 15 mg/d over the first 12 weeks according to clinical response). Changes in fasting plasma glucose (FPG), haemoglobin A1c (HbA1c), fasting insulin and its precursor peptides, and lipids were measured and safety was evaluated.

Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy.

Background: The efficacy of thiazolidinediones, as compared with other oral glucose-lowering medications, in maintaining long-term glycemic control in type 2 diabetes is not known.

Methods: We evaluated rosiglitazone, metformin, and glyburide as initial treatment for recently diagnosed type 2 diabetes in a double-blind, randomized, controlled clinical trial involving 4360 patients. The patients were treated for a median of 4.

Obesity is a major determinant of the association of C-reactive protein levels and the metabolic syndrome in type 2 diabetes.

The inflammatory factor C-reactive protein (CRP) and the fibrinolytic variables fibrinogen and plasminogen activator-1 (PAI-1) are associated with long-term cardiovascular morbidity. To determine the contribution of body adiposity (BMI), insulin sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR], and glycemia (HbA(1c) [A1C]) to the levels of these inflammatory and fibrinolytic variables in recently diagnosed ( View Article and Find Full Text PDF

Effects of rosiglitazone maleate when added to a sulfonylurea regimen in patients with type 2 diabetes mellitus and mild to moderate renal impairment: a post hoc analysis.

Background: Patients with type 2 diabetes mellitus (DM) and renal impairment whose disease is inadequately controlled on a sulfonylurea (SU) have limited oral combination treatment options.

Objective: This post hoc analysis assesses the efficacy and tolerability of the insulin sensitizer rosiglitazone maleate (RSG) when added to an SU treatment regimen in patients with type 2 DM with mild to moderate renal impairment that is inadequately controlled by SU monotherapy.

Methods: Data were pooled from 3 randomized, double-blind, placebo-controlled, parallel-group studies in which RSG or placebo was added to an SU (glibenclamide, gliclazide, or glipizide) treatment regimen for a period of 6 months.

Effect of rosiglitazone on insulin sensitivity and body composition in type 2 diabetic patients [corrected].

Objective: To investigate the effects of rosiglitazone (RSG) on insulin sensitivity and regional adiposity (including intrahepatic fat) in patients with type 2 diabetes.

Research Methods And Procedures: We examined the effect of RSG (8 mg/day, 2 divided doses) compared with placebo on insulin sensitivity and body composition in 33 type 2 diabetic patients. Measurements of insulin sensitivity (euglycemic hyperinsulinemic clamp), body fat (abdominal magnetic resonance imaging and DXA), and liver fat (magnetic resonance spectroscopy) were taken at baseline and repeated after 16 weeks of treatment.

A diabetes outcome progression trial (ADOPT): an international multicenter study of the comparative efficacy of rosiglitazone, glyburide, and metformin in recently diagnosed type 2 diabetes.

Objective: Therapies with metformin, sulfonylureas, or insulin improve glycemic control in the short term but do not prevent progressive islet beta-cell failure or long-term deterioration in glycemia. Our goal was to evaluate, in patients recently diagnosed with type 2 diabetes (<3 years), the long-term efficacy of monotherapy with rosiglitazone on glycemic control and on the progression of pathophysiological abnormalities associated with type 2 diabetes as compared with metformin or glyburide monotherapy.

Research Design And Methods: A Diabetes Outcome Progression Trial (ADOPT) is a randomized, double-blind, parallel-group study consisting of a screening visit, a 4-week placebo run-in, a 4-year treatment period, and an observational follow-up of approximately 3,600 drug-naïve patients with type 2 diabetes diagnosed within the previous 3 years.