Nateglinide alone and in combination with metformin improves glycemic control by reducing mealtime glucose levels in type 2 diabetes.

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 HbA1c, fasting plasma glucose (FPG), and mealtime glucose excursions. RESEARCH DESIGN AND METHODS: In this randomized double-blind study, patients with an HbA1c 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). HbA1c 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, HbA1c was reduced from baseline with nateglinide and metformin but was increased with placebo (-0.5, -0.8, and +0.5%, respectively; P < or = 0.0001). Changes in FPG followed the same pattern (-0.7, -1.6, and +0.4 mmol/l; P < or = 0.0001). Combination therapy was additive (HbA1c -1.4% and FPG -2.4 mmol/l; P < or = 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]0-130 min -2.1, -1.1, and -0.6 mmol x h(-1) x l(-1); p < or = 0.0001). An even greater effect was observed with combination therapy (AUC0-130 min -2.5 mmol x h(-1) x l(-1); P < or = 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 HbA1c, FPG, and postprandial hyperglycemia.

Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy, tolerability and safety compared to an angiotensin-converting enzyme inhibitor, lisinopril.

OBJECTIVE: To compare the efficacy, safety and tolerability of valsartan to an angiotensin-converting enzyme (ACE) inhibitor, lisinopril, and placebo in patients with mild-to-moderate essential hypertension. DESIGN: A total of 734 men and women were randomised in this multicentre, double-blind, optional titration, parallel group trial. Volunteers received valsartan 80 mg (n = 364), lisinopril 10 mg (n = 187) or placebo (n = 183) daily for 4 weeks, with subsequent titration of dose depending on response to treatment (valsartan 80 mg titrated to valsartan 160 mg once daily or valsartan 80 mg twice daily, lisinopril 10 mg titrated to lisonopril 20 mg once daily). Patients were assessed at 4, 8 and 12 weeks. MAIN OUTCOME MEASURES: The primary variable was change from baseline in mean sitting diastolic blood pressure (SDBP). Other efficacy variables included sitting systolic blood pressure (SSBP) and percentage of 'successful' responders (SDBP <90 mm Hg or > or =10 mm Hg reduction from baseline). RESULTS: All active treatment groups were shown to demonstrate significant reductions in SDBP compared to placebo at endpoint of therapy (least mean square reduction from baseline: valsartan 80/160 mg: -5.25 mm Hg (Cl -7.17, -3.34, P< 0.001); valsartan 80/80 mg twice daily: -5.63 mm Hg (Cl -7.51, -3.75, P< 0.001); lisinopril 10/20 mg: -6.93 mm Hg, (Cl -8.81, -5.05, P< 0.001). There were no statistically significant differences between the active treatment groups at endpoint of therapy. In patients requiring titration to a higher dose (placebo n = 142, valsartan 80/80 twice daily n = 124, valsartan 80/160 n = 114, lisinopril 10/20 n = 120), there were no significant treatment differences between valsartan 160 mg given as a single daily dose or as 80 mg twice daily (P = 0.658). Both valsartan and lisinopril produced similarly high percentages of 'successful' responders at endpoint of therapy. A somewhat higher frequency of drug related cough was observed in lisinopril treated patients (8%) compared to valsartan (1.1%) or placebo (0.5%). CONCLUSIONS: Valsartan 80 mg daily, with titration to 160 mg daily as required, provides similar antihypertensive efficacy to lisinopril 10 mg daily with titration to 20 mg daily. Valsartan provides a new antihypertensive agent with comparable efficacy to lisinopril and appears to be associated with a reduced incidence of cough.

Safety profile of benazepril in essential hypertension.

Data from clinical trials with benazepril suggest that the safety profile of benazepril is similar to that of other angiotensin-converting enzyme (ACE) inhibitors. Treatment-related side effects occurred in 20% of benazepril-treated patients and in 18% of patients receiving placebo. The most commonly reported side effects with benazepril were headache, dizziness, and fatigue. The incidence of side effects was not affected by the degree of hypertension, age, gender, race, dosage, or the degree of renal impairment. Side effects believed to be related to the pharmacologic action of ACE inhibitors as a class include symptomatic hypotension, which occurred at a relatively low rate with benazepril, and hyperkalemia and elevation of serum creatinine, which occurred to the same extent with benazepril as has been noted with other ACE inhibitors. The mechanism of cough as an ACE inhibitor side effect is unknown; the incidence was similar to that with other ACE inhibitors. Rash and taste disturbance have occurred rarely with benazepril. The incidence of neutropenia and of proteinuria was the same in both the benazepril and placebo groups. Renal failure in hypertensive patients treated with benazepril has not been reported. Overall, benazepril is generally well tolerated by hypertensive patients. The incidence of most side effects is comparable to that with other ACE inhibitors and placebo.

Benazepril en el tratamiento de pacientes hipertensos de edad madura y ancianos / Benazepril of the treatment the hypertensive patients the mature age and elderly

Se examinaron la eficacia y la tolerabilidad del benazepril en 95 pacientes hipertensos de edad madura (>55 años) y 235 ancianos (>65 años). El grupo de edad madura participó en un estudio randomizado en doble-ciego, de 6 semanas de duración, comparando el benazepril (10-20 mg una vez al día) con hidroclorotiazida (25-50 mg una vez al día). El grupo de los ancianos participó en un total de 13 estudios randomizados en doble-ciego de hasta 24 semanas de duración, comparando el benazepril (10-80 mg/día) con otras drogas antihipertensivas. También se evaluaron benazepril e hidroclorotiazida, en combinación, en 32 pacientes ancianos y 209 no ancianos. En los pacientes de edad madura, el benazepril redujo sustancialmente la presión sanguínea sistólica y diastólica, al cabo de una terapéutica de 6 semanas de duración, la proporción de pacientes, que exitosamente lograron obtener el objetivo de presión arterial ha sido significativamente superior que en el grupo de hidroclorotiazida. En el grupo de los ancianos, el benazepril, en un régimen de una o dos veces al día, también redujo sustancialmente la presión sistólica y diastólica. Su efecto antihipertensivo fue mejorado mediante la adición de hidroclorotiazida una vez al día y comparado favorablemente con el resultado obtenido en pacientes más jóvenes, tanto en monoterapia como en tratamientos combinados. La tolerancia y la inocuidad globales del benazepril en los pacientes de edad madura y ancianos fueron buenas y similares a las observadas en pacientes más jóvenes.