Strategies for Optimizing Glycemic Control and Cardiovascular Prognosis in Patients With Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (DM) is a major cardiovascular (CV) risk factor and, as such, is considered a coronary artery disease risk equivalent. Although glycemic control is associated with decreased CV events epidemiologically, many prospective clinical trials have failed to conclusively demonstrate that aggressive glycemic control improves the CV prognosis of patients with type 2 DM, especially those with long-standing DM. Many therapies for type 2 DM with widely divergent mechanisms of action are available. Some of these drugs, in addition to their glucose-lowering actions, have properties that may reduce or increase CV events. Agents that lower both insulin resistance and postprandial hyperglycemia while at the same time avoiding hypoglycemia may be beneficial for CV health. This article reviews the evidence regarding the use of these agents and appropriate glycemic control targets for improving the adverse CV prognosis associated with type 2 DM. We conducted a systematic review of English articles using MEDLINE and the Cochrane Controlled Trials Register (1970-2010) using the following search terms: cardiovascular disease, randomized trials, hypoglycemia, and insulin resistance

Nusinersen versus Sham Control in Later-Onset Spinal Muscular Atrophy

International audienceBACKGROUND Nusinersen is an antisense oligonucleotide drug that modulates pre-messenger RNA splicing of the survival motor neuron 2 (SMN2) gene. It has been developed for the treatment of spinal muscular atrophy (SMA). METHODS We conducted a multicenter, double-blind, sham-controlled, phase 3 trial of nusinersen in 126 children with SMA who had symptom onset after 6 months of age. The children were randomly assigned, in a 2: 1 ratio, to undergo intrathecal administration of nusinersen at a dose of 12 mg (nusinersen group) or a sham procedure (control group) on days 1, 29, 85, and 274. The primary end point was the least-squares mean change from baseline in the Hammersmith Functional Motor Scale-Expanded (HFMSE) score at 15 months of treatment; HFMSE scores range from 0 to 66, with higher scores indicating better motor function. Secondary end points included the percentage of children with a clinically meaningful increase from baseline in the HFMSE score (>= 3 points), an outcome that indicates improvement in at least two motor skills. RESULTS In the prespecified interim analysis, there was a least-squares mean increase from baseline to month 15 in the HFMSE score in the nusinersen group (by 4.0 points) and a least-squares mean decrease in the control group (by -1.9 points), with a significant between-group difference favoring nusinersen (least-squares mean difference in change, 5.9 points; 95% confidence interval, 3.7 to 8.1; P< 0.001). This result prompted early termination of the trial. Results of the final analysis were consistent with results of the interim analysis. In the final analysis, 57% of the children in the nusinersen group as compared with 26% in the control group had an increase from baseline to month 15 in the HFMSE score of at least 3 points (P< 0.001), and the overall incidence of adverse events was similar in the nusinersen group and the control group (93% and 100%, respectively). CONCLUSIONS Among children with later-onset SMA, those who received nusinersen had significant and clinically meaningful improvement in motor function as compared with those in the control group. (Funded by Biogen and Ionis Pharmaceuticals; CHERISH ClinicalTrials. gov number, NCT02292537.

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes