The addition of eplerenone to optimal medical therapy reduces morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure.

The benazepril-amlodipine combination was superior to the benazepril-hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events. (ClinicalTrials.gov number, NCT00170950.)

OBJECTIVE -To evaluate the efficacy and tolerability of nateglinide and metformin alone and in combination in type 2 diabetic patients inadequately controlled by diet, focusing on changes in HbA 1c , fasting plasma glucose (FPG), and mealtime glucose excursions.RESEARCH DESIGN AND METHODS -In this randomized double-blind study, patients with an HbA 1c level between 6.8 and 11.0% during a 4-week placebo run-in received 24 weeks' treatment with 120 mg nateglinide before meals (n = 179), 500 mg metformin three times a day (n = 178), combination therapy (n = 172), or placebo (n = 172). HbA 1c and FPG were evaluated regularly, and plasma glucose levels were determined after Sustacal challenge at weeks 0, 12, and 24. Hypoglycemia and other adverse events were recorded.RESULTS -At study end point, HbA 1c was reduced from baseline with nateglinide and metformin but was increased with placebo (Ϫ0.5, Ϫ0.8, and ϩ0.5%, respectively; P Յ 0.0001). Changes in FPG followed the same pattern (Ϫ0.7, Ϫ1.6, and ϩ0.4 mmol/l; P Յ 0.0001). Combination therapy was additive (HbA 1c Ϫ1.4% and FPG Ϫ2.4 mmol/l; P Յ 0.01 vs. monotherapy). After Sustacal challenge, there was a greater reduction in mealtime glucose with nateglinide monotherapy compared with metformin monotherapy or placebo (adjusted area under the curve [AUC] 0-130min Ϫ2.1, Ϫ1.1, and Ϫ0.6 mmol и h Ϫ1 и l Ϫ1 ; P Յ 0.0001). An even greater effect was observed with combination therapy (AUC 0-130min Ϫ2.5 mmol и h Ϫ1 и l Ϫ1 ; P Յ 0.0001 vs. metformin and placebo). All regimens were well tolerated.CONCLUSIONS -Nateglinide and metformin monotherapy each improved overall glycemic control but by different mechanisms. Nateglinide decreased mealtime glucose excursions, whereas metformin primarily affected FPG. In combination, nateglinide and metformin had complementary effects, improving HbA 1c , FPG, and postprandial hyperglycemia.

OBJECTIVE -This study compared the effects of nateglinide, glyburide, and placebo on postmeal glucose excursions and insulin secretion in previously diet-treated patients with type 2 diabetes.RESEARCH DESIGN AND METHODS -This randomized, double-blind, placebocontrolled multicenter study was conducted in 152 patients who received either nateglinide (120 mg before three meals daily, n ϭ 51), glyburide (5 mg q.d. titrated to 10 mg q.d. after 2 weeks, n ϭ 50), or placebo (n ϭ 51) for 8 weeks. Glucose, insulin, and C-peptide profiles during liquid meal challenges were measured at weeks 0 and 8. At weeks Ϫ1 and 7, 19-point daytime glucose and insulin profiles, comprising three solid meals, were measured.RESULTS -During the liquid-meal challenge, nateglinide reduced the incremental glucose area under the curve (AUC) more effectively than glyburide (⌬ ϭ Ϫ4.94 vs. Ϫ2.71 mmol ⅐ h/l, P Ͻ 0.05), whereas glyburide reduced fasting plasma glucose more effectively than nateglinide (⌬ ϭ Ϫ2.9 vs. Ϫ1.0 mmol/l, respectively, P Ͻ 0.001). In contrast, C-peptide induced by glyburide was greater than that induced by nateglinide (⌬ ϭ ϩ1.83 vs. ϩ0.95 nmol ⅐ h/l, P Ͻ 0.01), and only glyburide increased fasting insulin levels. During the solid meal challenges, nateglinide and glyburide elicited similar overall glucose control (⌬ 12-h incremental AUC ϭ Ϫ13.2 vs. Ϫ15.3 mmol ⅐ h/l), but the insulin AUC induced by nateglinide was significantly less than that induced by glyburide (⌬ 12-h AUC ϭ ϩ866 vs. ϩ1,702 pmol ⅐ h/l, P ϭ 0.01).CONCLUSIONS -This study demonstrated that nateglinide selectively enhanced early insulin release and provided better mealtime glucose control with less total insulin exposure than glyburide. Diabetes Care 24:983-988, 2001