Effect of ranolazine on glycaemic control in patients with type 2 diabetes treated with either glimepiride or metformin.

AIM: To report the results of two phase III trials assessing the efficacy of ranolazine for glycaemic control in patients with type 2 diabetes on metformin or glimepiride background therapy. METHODS: In two double-blind trials we randomized 431 and 442 patients with type 2 diabetes to ranolazine 1000 mg twice daily versus placebo added to either glimepiride (glimepiride add-on study) or metformin background therapy (metformin add-on study). Patients receiving ranolazine added to metformin had their metformin dose halved (with the addition of a metformin-matched placebo) relative to the placebo group to correct for a metformin-ranolazine pharmacokinetic interaction. The primary endpoint of the trials was the change from baseline in glycated haemoglobin (HbA1c) at week 24. RESULTS: When added to glimepiride, ranolazine caused a 0.51% least squares mean [95% confidence interval (CI) 0.71, 0.32] decrease from baseline in HbA1c at 24 weeks relative to placebo and roughly doubled the proportion of patients achieving an HbA1c of <7% (27.1 vs 14.1%; p = 0.001). When added to metformin background therapy, there was no significant difference in the 24-week HbA1c change from baseline [placebo-corrected LS mean difference -0.11% (95% CI -0.31, 0.1)]. CONCLUSIONS: Compared with placebo, addition of ranolazine in patients with type 2 diabetes treated with glimepiride, but not metformin, significantly reduced HbA1c over 24 weeks. The decreased dose of metformin used in the metformin add-on study complicates the interpretation of this trial. Whether an effective regimen of ranolazine added to metformin for glycaemic control can be identified remains unclear.

Oral manifestations of drug therapy.

Increasingly, patients with complicated medical problems are coming to dental offices for treatment. These patients report using a variety of medications to control one or more chronic conditions. Many of these medications produce changes in the mouth because of toxic overdoses, side effects, allergic reactions, or as a consequence of the primary action of the drug. These effects include: xerostomia, gingival hyperplasia, candidiasis, mucositis, stomatopyrosis, gingival bleeding, petechia, salivary gland problems, intrinsic stain, cheilitis, erythema multiforme, lichen planus, ulcerations, taste changes, tardive dyskinesias, and soft tissue pigmentation. This article discusses presentations and causes of oral changes secondary to systemic drug use.

Effects of pulsed external augmentation of diastolic pressure on coronary and systemic hemodynamics in patients with coronary artery disease.

The purpose of this study was to define the effects of pulsed external diastolic pressure augmentation on coronary and systemic hemodynamics in 14 men with coronary artery disease and normal left ventricular function. Coronary sinus and great vein blood flow (thermodilution) and systemic hemodynamics were measured before, during, and after timed lower extremity compression, augmenting peak diastolic pressure to within 5 mm Hg of systolic pressure. Systolic and diastolic pressure-time indices were calculated from the high-fidelity micromanometer left ventricular-aortic recordings. External counterpulsation increased mean arterial pressure (108 +/- 11 [1 SD] to 114 +/- 12 mm Hg, p less than 0.01) and the diastolic pressure-time index (440 +/- 51 to 498 +/- 82 units, p less than 0.01), with no change in the systolic pressure-time index, absolute coronary sinus, or great cardiac vein blood flow. External diastolic pressure augmentation did not affect heart rate, right heart hemodynamics, cardiac output, or calculated myocardial oxygen consumption. An unanticipated finding was a greater than or equal to 10% reduction in peak systolic pressure during external diastolic pressure augmentation in 8 of 14 patients. Despite minimal changes in absolute myocardial blood flow and oxygen consumption, the increase in the diastolic pressure-time/systolic pressure-time index ratio suggests that subendocardial perfusion may be favorably influenced by diastolic pressure augmentation and may explain the previously reported clinical benefits of external counterpulsation in some patients with ischemic heart disease.