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This study compared the efficacy and tolerability of eplerenone and enalapril in 499 patients with stage 1 or 2 hypertension who were randomized to receive eplerenone or enalapril for 6 months in a 3-step titration-to-effect study. After 6 months, patients whose diastolic blood pressure (BP) was <90 mm Hg had their dosages down-titrated were followed for an additional 6 months. Diastolic BP was the primary end point. Eplerenone was as effective as enalapril in reducing both systolic BP (eplerenone, -14.5 mm Hg; enalapril, -12.7 mm Hg; p = 0.199) and diastolic BP (eplerenone, -11.2 mm Hg; enalapril, -11.3 mm Hg; p = 0.910) at 6 months. BP reductions at 12 months were also similar between groups (-16.5/-13.3 mm Hg for eplerenone, -14.8/-14.1 mm Hg for enalapril; p = 0.251 and 0.331, respectively). Withdrawal rates for adverse events (eplerenone 7.9%, enalapril 9.3% at 6 months) and treatment failures (eplerenone 23.3%, enalapril 22.8% at 6 months) were also equivalent. Approximately 2/3 of each group had normal BP with monotherapy treatment at 6 months. BP response was independent of renin levels in the eplerenone group, but not in the enalapril group. Both agents reduced albuminuria in patients who had an elevated value at baseline, with significantly greater improvement in patients treated with eplerenone versus enalapril (-61.5% vs -25.7%; p = 0.01). Both agents were similarly well tolerated, and there was no increased incidence of any sexual adverse events in the eplerenone group. Patients taking enalapril had a higher rate of cough. Both agents increased serum potassium levels, but <1% in each group reported adverse events from hyperkalemia. Eplerenone was as effective as enalapril as monotherapy in patients with stage 1 or 2 hypertension, was more effective in reducing albuminuria, and was well tolerated for 12 months.

Background: Coronary heart disease is the major cause of mortality in individuals with diabetes mellitus (DM). Given the increasingly aggressive low-density lipoprotein cholesterol (LDL-C) goals for patients with DM set by the National Cholesterol Education Program Adult Treatment Panel III and the American Diabetes Association, many patients remain above target. Treatment with thiazolidinediones (TZDs) improves glycemic control but does not lower (and may raise) LDL-C concentrations., Objective: This study assessed the lipid-modifying efficacy and tolerability of adding the hydroxymethylglutaryl coenzyme A-reductase inhibitor simvastatin to existing TZD therapy in patients with type 2 DM., Methods: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial. Patients with type 2 DM who were taking a stable dose of pioglitazone or rosiglitazone and had a glycosylated hemoglobin (HbA1c) value < or =9.0% and an LDL-C concentration > 100 mg/dL were randomized to receive simvastatin 40 mg (the recommended initial dose for patients with DM) or placebo for 24 weeks. The primary end point was the effect of treatment on LDL-C concentrations. Other lipid, lipoprotein, and safety measures were also assessed., Results: Two hundred fifty-three patients (127 [50.2%] men, 126 [49.8%] women; mean age, 56 years) were randomized to treatment (123 simvastatin, 130 placebo). At the end of the study, mean LDL-C concentrations were reduced 34.)% from baseline (from 134.3 to 89.5 mg/dL) in the simvastatin group and were unchanged in the placebo group (P<0.001). Simvastatin produced significant reductions in concentrations of total cholesterol, triglycerides (TG), non-high-density lipoprotein cholesterol, and apolipoprotein (apo) B compared with placebo (all, P<0.001 ) and significant increases in concentrations of high-density lipoprotein cholesterol (HDL-C) ( P=0.002 ) and apo A-I ( P=0.006 ). In patients who had not attained target concentrations of LDL-C (<100 mg/dL), TG (<150 mg/dL), or HDL-C (>45 mg/dL) at baseline, significantly more simvastatin recipients had achieved these goals at the end of the study compared with placebo recipients (LDL-C: 67.3% vs 5.2%, respectively, P<0.001; HDL-C: 95.3% vs 83.6%, P<0.05; TG: 40.8% vs 11.0%, P<0.001 ). Simvastatin was well tolerated, and no clinically meaningful differences in the incidence of serious adverse events, treatment-related adverse events, or discontinuations due to adverse events were observed between groups. There were no significant between-group differences in glycemic control (HbA1c) or concentrations of fasting insulin, creatine phosphokinase, or hepatic transaminases., Conclusion: Simvastatin was an effective and generally well tolerated treatment for hyperlipidemia when used in combination with TZD therapy in this population of patients with type 2 DM.

Purpose: To evaluate the efficacy and tolerability of pioglitazone in combination with a sulfonylurea in the treatment of type 2 diabetes mellitus., Subjects and Methods: This 16-week, double-blind study included patients on a stable regimen of a sulfonylurea for > or = 30 days and with a glycosylated hemoglobin (HbA1C) level > or = 8.0%. Patients were randomly assigned to receive once daily pioglitazone 15 mg (n = 184), pioglitazone 30 mg (n = 189), or placebo plus sulfonylurea (n = 187)., Results: Patients receiving pioglitazone + sulfonylurea had significant (P < 0.05) decreases from baseline in HbA1C and fasting plasma glucose levels compared with patients treated with placebo + sulfonylurea. As compared with placebo, HbA1C decreased by 0.9% (95% confidence interval [CI]: 0.06% to 1.2%) with pioglitazone 15 mg and 1.3% (CI: 1% to 1.6%) with 30 mg pioglitazone; fasting plasma glucose levels decreased by 39 mg/dL (95% CI: 27 to 52 mg/dL) with pioglitazone 15 mg and by 58 mg/dL (95% CI: 46-70 mg/dL) with 30 mg pioglitazone. Both pioglitazone + sulfonylurea groups had significant (P < 0.05) mean percent decreases in triglyceride levels (17%, 95% CI: 6% to 27% for 15 mg; 26%, 95% CI: 16% to 36% for 30 mg) and increases in high-density lipoprotein cholesterol levels (6%, 95% CI: 1% to 11% for 15 mg; 13%, CI: 8% to 18% for 30 mg) compared with placebo + sulfonylurea. There were small but statistically significant mean percent increases in low-density lipoprotein cholesterol levels in all groups. Pioglitazone was well tolerated, and the rates of adverse events were similar in all groups., Conclusion: In patients with type 2 diabetes, pioglitazone plus sulfonylurea significantly improves HbA1C and fasting plasma glucose levels with beneficial effects on serum triglyceride and HDL-cholesterol levels.

The effect of glipizide alone and glipizide preceded by a short course of insulin therapy (10 weeks) was studied in 69 patients with non-insulin-dependent diabetes mellitus (NIDDM) in a 10-month study. The patients were obese, had poor glycemic control, and, in all patients, first-generation sulfonylurea therapy had failed. The majority were Mexican-Americans, an ethnic population with a high incidence of NIDDM and insulin resistance. Plasma glucose levels were monitored using the eight-point [Saarstedt] series. In the group receiving glipizide alone, mean fasting plasma glucose levels decreased from 255.9 mg/dl at baseline to 228.7 mg/dl at the end of the study; two-hour postprandial glucose levels decreased from 280.1 to 260.5 mg/dl; glycosylated hemoglobin decreased from 9.1 to 7.4 percent; and post-Sustacal C-peptide levels increased from 0.7 to 1.0 pmol/ml. In the group receiving insulin/glipizide, mean fasting plasma glucose levels decreased from 241.1 mg/dl at baseline to 217.0 mg/dl; two-hour postprandial glucose levels increased from 267.2 to 279.0 mg/dl; glycosylated hemoglobin decreased from 9.1 to 7.5 percent; and post-Sustacal C-peptide levels increased from 0.6 to 1.0 pmol/ml. At the end of 10 weeks, insulin administration was associated with a more rapid decrease in the levels of fasting plasma glucose, two-hour postprandial glucose, and glycosylated hemoglobin, but there was no significant difference between the two therapies by the end of the study. Both regimens had a positive influence on reducing the total cholesterol/high-density lipoprotein ratio. More patients in the group receiving insulin/glipizide withdrew from the study, which may have been due to difficulties associated with insulin administration. In conclusion, there does not appear to be a prolonged effect of insulin treatment on the post-receptor defect. Some patients in whom first-generation oral agents fail may not have to be given permanent insulin therapy, especially those with fasting plasma glucose levels of less than 200 mg/dl. There was no overall difference between these treatments with respect to glycemic control or lipoprotein profiles. In the interests of simplifying both therapy and monitoring, enhancing patient compliance, and achieving cost reductions, therapy with glipizide alone ultimately may be sufficient for cases in which immediate control is unnecessary (for example, patients with asymptomatic hyperglycemia, and in the absence of hyperlipidemia and vascular disease).