RESUMEN
AIM: To assess and compare the efficacy and safety of liraglutide with those of glimepiride, both in combination with metformin for the treatment of type 2 diabetes in Asian population from China, South Korea and India. METHODS: A 16-week, randomized, double-blind, double-dummy, four-arm, active control trial was carried out. In total, 929 subjects with type 2 diabetes with a mean (±s.d.) age of 53.3 ± 9.5 years, HbA1(c) of 8.6 ± 1.0% and body weight of 68.1 ± 11.7 kg were randomized (liraglutide 0.6, 1.2 or 1.8 mg once daily or glimepiride 4 mg once daily all in combination with metformin: 1 : 1 : 1 : 1). One subject withdrew immediately after randomization and before exposure. RESULTS: HbA1(c) was significantly reduced in all groups compared with baseline. Treatment with liraglutide 1.2 and 1.8 mg was non-inferior to glimepiride (mean HbA1(c) reduction: 1.36% points, 1.45% points and 1.39% points, respectively). No significant difference was shown in the percentage of subjects reaching American Diabetes Association HbA1(c) target <7% or American Association of Clinical Endocrinologists target ≤6.5% between liraglutide 1.2 and 1.8 mg and glimepiride. Liraglutide was associated with a 1.8-2.4 kg mean weight reduction, compared with a 0.1 kg mean weight gain with glimepiride. Liraglutide led to a significantly greater reduction in systolic blood pressure (SBP) compared with glimepiride. Two subjects in the glimepiride group reported major hypoglycaemia while none in the liraglutide groups. Liraglutide was associated with about 10-fold lower incidence of minor hypoglycaemia than glimepiride. Gastrointestinal disorders were the most common adverse events (AEs) for liraglutide, but were transient and resulted in few withdrawals. CONCLUSIONS: In Asian subjects with type 2 diabetes, once-daily liraglutide led to improvement in glycaemic control similar to that with glimepiride but with less frequent major and minor hypoglycaemia. Liraglutide also induced a significant weight loss and reduced SBP and was generally well tolerated. The most frequently reported AE was transient nausea. The effect of liraglutide in this Asian population is comparable to the effects seen in Caucasian, African American and Hispanic populations in global liraglutide phase 3 trials.
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Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Péptido 1 Similar al Glucagón/análogos & derivados , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Compuestos de Sulfonilurea/administración & dosificación , Pérdida de Peso/efectos de los fármacos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Presión Sanguínea/fisiología , China , Diabetes Mellitus Tipo 2/fisiopatología , Método Doble Ciego , Quimioterapia Combinada , Femenino , Péptido 1 Similar al Glucagón/administración & dosificación , Humanos , India , Liraglutida , Masculino , Persona de Mediana Edad , República de Corea , Pérdida de Peso/fisiología , Adulto JovenRESUMEN
AIM: The Physicians' Routine Evaluation of Safety and Efficacy of NovoMix 30 Therapy (PRESENT) study aims to assess the safety and efficacy of biphasic insulin aspart 30 (BIAsp 30) in patients with type 2 diabetes mellitus in routine clinical practice. METHODS: This was a 6-month, prospective, multinational, multiethnic observational study involving 21 977 patients from 13 countries (India, Iraq, Jordan, Kuwait, Lebanon, Qatar, Romania, Russia, Saudi Arabia, South Africa, South Korea, Turkey and the United Arab Emirates). The patients were transferred to BIAsp 30 with or without oral antidiabetic drugs (OADs) from prior treatment with OAD (n = 8583), insulin (n = 5942), OAD + insulin (n = 4673) or diet (i.e. treatment naive) (n = 1707). One thousand and seventy-two patients had incomplete or no information on previous treatment. RESULTS: At 3 and 6 months, significant reductions from baseline were observed in the mean haemoglobin A(1c) (HbA(1c)) (-1.33 and -1.81%), fasting plasma glucose (-3.02 and -3.74 mmol/l) and postprandial plasma glucose (-4.76 and -5.82 mmol/l) (p < 0.001). A significantly greater proportion of patients achieved target HbA(1c) of less than 7% at 3 months (15.3%) and 6 months (27.7%) compared with baseline (4.8%) (p < 0.001). Overall, the mean HbA(1c) at 6 months was lowered in patients regardless of prior treatment: -2.15% (OAD), -1.45% (insulin), -1.47% (OAD + insulin) and -2.35% (treatment naive). In the overall cohort, the rate of total hypoglycaemia was reduced from 5.4 events per patient-year at baseline to 2.2 events per patient-year at study end (p < 0.001). Among prior treatment subgroups, the rates of total hypoglycaemia were reduced from 2.5 to 2.1 events per patient-year in the OAD group, from 9.6 to 2.2 events per patient-year in the insulin group and from 7.6 to 2.5 events per patient-year in the OAD + insulin group but were increased from 1.0 to 1.8 events per patient-year in the treatment-naive group (p < 0.001). There were 444 adverse drug reactions (ADRs), including 13 serious ADRs: lipodystrophy (three events), symptoms of generalized hypersensitivity (two events), acute painful neuropathy (one event), worsening of diabetic retinopathy (one event), oedema (one event) and unspecified ADRs (five events). CONCLUSION: The use of BIAsp 30 monotherapy or in combination with OADs in clinical practice was effective and safe in patients with poorly controlled type 2 diabetes mellitus.
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Glucemia/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Insulina/análogos & derivados , Insulinas Bifásicas , Diabetes Mellitus Tipo 2/sangre , Medicina Familiar y Comunitaria , Humanos , Hipoglucemia/metabolismo , Insulina/sangre , Insulina/uso terapéutico , Insulina Aspart , Insulina Isófana , Resultado del TratamientoRESUMEN
AIM: To evaluate the efficacy and safety of adding biphasic insulin aspart 30 (BIAsp30; NovoMix 30) to existing oral antidiabetic agents (OADs) vs. optimizing OADs in a subgroup of Western Pacific patients with type 2 diabetes inadequately controlled on oral monotherapy or oral combination therapy. METHODS: This 26-week, multi-centre, open-labelled, randomized, two-arm parallel trial consisted of a 2-week screening period, followed by 24 weeks of treatment. Subjects randomized to BIAsp30 treatment (n = 129) received BIAsp30 once daily (o.d.) at dinnertime between Week 2 and Week 14, and those not reaching treatment targets were switched to twice daily (b.i.d.) BIAsp30 at Week 14 (n = 50). Subjects randomized to the OAD-only arm (n = 63) continued with their previous OAD treatment and, in an attempt to reach treatment goals, the dose was optimized (but OAD unchanged) in accordance to local treatment practice and labelling. RESULTS: Significantly greater reductions in HbA(1c) over Weeks 0-13 with BIAsp30 (o.d.) vs. OAD-only treatment (1.16 vs. 0.58%; p < 0.001), and over Weeks 0-26, with BIAsp30 (o.d.) and BIAsp30 (b.i.d.) treatments vs. OAD-only treatment (1.24 vs. 1.34 vs. 0.67%; p < 0.01). Hypoglycaemic episodes were reported in 54% of the patients in BIAsp30 (o.d. and b.i.d. pooled) and 30% of the patients in OAD-only group. All episodes were minor or symptomatic, except for one in each treatment group, which was major. CONCLUSIONS: Initiating BIAsp30 treatment is a safe and more effective way to improve glycaemic control in Western Pacific patients with type 2 diabetes inadequately controlled with oral monotherapy or oral combination therapy compared with optimizing oral combination therapy alone. In patients not reaching treatment target on BIAsp30 (o.d.), treatment with BIAsp30 (b.i.d.) should be considered.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Insulina/análogos & derivados , Insulinas Bifásicas , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Hipoglucemiantes/efectos adversos , Insulina/administración & dosificación , Insulina/efectos adversos , Insulina Aspart , Insulina Isófana , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Eight patients with mild heart failure were treated in random order for 1 week with 2 mg bumethanide at 0800 and 1200 (treatment 1) h, 1 mg bumethanide at 0800, 1200, 1800, 2200 (treatment 2) and 5 mg bendroflumethiazide at 0800 and 1800 (treatment 3) h. The 'quality of life' did not differ significantly between the three treatment periods. At the presumed trough of the diuretic effect the circulating blood volume was largest during treatment 1; it was 6.3% smaller during treatment 2 (P < 0.02) and 6.7% lower during treatment 3 (P < 0.05). In comparison with treatment 1, the maximal increase in rate-pressure product during physical exercise was 24.6% higher in treatment 3. Compared with treatment 1 the area under the curve (AUC) for plasma lactate during physical exercise was 14% lower during treatment 2 (P < 0.05) and 18% lower during treatment 3 (P < 0.01). These findings suggest that the type of program for diuretic therapy influences the magnitude of inevitable diurnal fluctuations in body fluids, the ability of the heart to work and the ability of the body to adjust to the oxygen demand.
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Diuréticos/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Bendroflumetiazida/administración & dosificación , Bendroflumetiazida/uso terapéutico , Volumen Sanguíneo/efectos de los fármacos , Bumetanida/administración & dosificación , Bumetanida/uso terapéutico , Ritmo Circadiano , Diuréticos/administración & dosificación , Esquema de Medicación , Ejercicio Físico/fisiología , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/fisiopatología , Humanos , Lactatos/sangre , Ácido Láctico , Masculino , Persona de Mediana EdadRESUMEN
The effects of coenzyme Q10 (CoQ) and captopril on functional capacity, hemodynamics and survival were studied in 154 rats that recovered after experimental myocardial infarction. Rats were randomized into four groups receiving either CoQ, captopril, a combination of the two drugs or 1 ml of tap water once daily for 12 weeks from the day of coronary artery ligation. CoQ as well as captopril and the combined treatment significantly improved exercise capacity as evaluated by lactate production during a standardized treadmill exercise test. No significant changes in heart rate or mean blood pressure were observed during the study in the captopril-treated group. CoQ treatment increased the maximum heart rate significantly, whereas no effect on mean blood pressure was observed. Both captopril and CoQ decreased pulmonary congestion. Furthermore, the data may suggest that captopril prevents right ventricular hypertrophy seen in placebo-treated rats with large infarcts. This was not observed after CoQ treatment. Captopril treatment improved 3-month probability of survival (93%) as compared with placebo (74%) (P less than .05). CoQ and the combined treatment tended to improve survival, but this was, however, not statistically significant.
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Captopril/farmacología , Infarto del Miocardio/fisiopatología , Ubiquinona/farmacología , Animales , Peso Corporal/efectos de los fármacos , Captopril/administración & dosificación , Coenzimas , Sinergismo Farmacológico , Metabolismo Energético/efectos de los fármacos , Femenino , Insuficiencia Cardíaca/tratamiento farmacológico , Hemodinámica/efectos de los fármacos , Infarto del Miocardio/mortalidad , Tamaño de los Órganos/efectos de los fármacos , Ratas , Tasa de Supervivencia , Ubiquinona/administración & dosificación , Ubiquinona/sangreRESUMEN
The aim of this study was to investigate the time course of deterioration of functional capacity in the rat after ligation of the left coronary artery. Functional capacity was evaluated from the increase in blood lactate concentrations in 109 rats during a standardised treadmill test. Animals with myocardial infarction were compared with sham operated and normal controls. Functional capacity was followed during a 13 week period and estimations of the functional capacity were performed 1, 3, 7, 9 and 13 weeks after infarction. Coronary artery ligation produced a significant reduction in functional capacity, averaging 47% (p less than 0.01) over the first 3 weeks after myocardial infarction, irrespective of infarct size. In rats with large infarcts, functional capacity remained essentially unchanged throughout the observation period, but rats with small infarcts improved gradually until their measured exercise response was completely normal at the end of the 13 week period.
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Infarto del Miocardio/fisiopatología , Animales , Vasos Coronarios , Prueba de Esfuerzo , Femenino , Hemodinámica , Lactatos/sangre , Ácido Láctico , Ligadura , Infarto del Miocardio/sangre , Miocardio/patología , Ratas , Ratas Endogámicas , Factores de TiempoRESUMEN
The possible role of atrial natriuretic peptides (ANP) for the adaptive changes in renal Na excretion during chronic renal failure was studied in 5/6 nephrectomized (NX) rats maintained on a normal (100 mmol/kg) and a high (800 mmol/kg) Na diet. Atrial content of natriuretic substances was determined by bioassay and plasma ANP by radioimmunoassay. Nephrectomized rats showed a twofold increase in plasma ANP irrespective of their Na intake. Atrial ANP content was increased by high Na diet but unchanged by NX. Nephrectomized rats maintained on high Na diet showed partial depletion of atrial ANP stores. There were no significant changes in the volume fraction of atrial granules determined. The results suggest that ANP is involved in the regulation of renal Na excretion during chronic renal failure and acute Na loading; other mechanisms are probably involved in the adaption to chronic Na loading.