A randomized, parallel group, double-blind, multicentre study comparing the efficacy and safety of Avandamet (rosiglitazone/metformin) and metformin on long-term glycaemic control and bone mineral density after 80 weeks of treatment in drug-naïve type 2 diabetes mellitus patients.

AIM: The purpose of this study was to evaluate if superior glycaemic control could be achieved with Avandamet® (rosiglitazone/metformin/AVM) compared with metformin (MET) monotherapy, and if glycaemic effects attained with AVM are durable over 18 months of treatment. Bone mineral density (BMD) and bone biomarkers were evaluated in a subgroup of patients. METHODS: This was a phase IV, randomized, double-blind, multi-centre study in 688, drug naÏve, male and female patients who had an established clinical diagnosis of type 2 diabetes mellitus (T2DM). Patients were randomized in a 1 : 1 ratio either to AVM or MET. RESULTS: As initial therapy in patients with T2DM, AVM was superior to MET in achieving statistically significant reductions in glycated haemoglobin (HbA1c) (p < 0.0001) and fasting plasma glucose (FPG) (p < 0.001), with more patients reaching recommended HbA1c and FPG targets for intensive glycaemic control. The glycaemic effects attained with AVM compared to MET monotherapy were durable over 18 months of treatment. In the bone substudy, AVM was associated with a significantly lower BMD in comparison with MET at week 80 in the lumbar spine and total hip (p < 0.0012 and p = 0.0005, respectively). Between-treatment differences were not statistically significant for distal one-third of radius BMD, femoral neck BMD or total BMD. CONCLUSION: Superior glycaemic control was achieved with AVM compared with MET monotherapy. The superior glycaemic effects were shown to be durable over 18 months of treatment. AVM was associated with a significantly reduced BMD in comparison with MET at week 80 in the lumbar spine and total hip.

Effect of carvedilol on survival and hemodynamics in patients with atrial fibrillation and left ventricular dysfunction: retrospective analysis of the US Carvedilol Heart Failure Trials Program.

BACKGROUND: Atrial fibrillation (AF) is present in a significant number of patients with congestive heart failure (CHF) caused by left ventricular dysfunction and is associated with significant morbidity and increased mortality rates. Thus it is necessary to establish therapy to improve the outcome in this high-risk population. METHODS: We conducted a retrospective analysis of data from the US Carvedilol Heart Failure Trials Program and identified patients with AF at the time of enrollment. In these trials, 1094 patients with at least 3 months of heart failure symptoms and an ejection fraction < or = 0.35 were randomly assigned to receive carvedilol or placebo in a double-blind, stratified program according to performance on an exercise test. RESULTS: One hundred thirty-six patients with concomitant AF and CHF were identified during the screening visit (84 assigned to carvedilol and 52 to placebo). Therapy with carvedilol resulted in a significant improvement in left ventricular ejection fraction (from 23% to 33% with carvedilol and from 24% to 27% with placebo, P =.001). The physician global assessment improved in a greater number of patients treated with carvedilol than in those treated with placebo (71% vs 48%, P =.025). A trend toward a reduction in the combined end point of death or CHF hospitalization was also observed (19% in patients treated with placebo and 7% in patients on carvedilol; relative risk, 0.35; 95% confidence interval, 0.12, 1.02; P =.055). CONCLUSIONS: In patients with AF complicating CHF, carvedilol significantly improves left ventricular ejection fraction and physician global assessment and probably reduces the combined end point of CHF hospitalizations or death.