RESUMO
Despite the current guideline's recommendation of a timely stepwise intensification therapy, the "clinical inertia", termed as the delayed treatment intensification, commonly exists in the real world, which may be partly due to the relatively little substantial evidence and no clear consensus regarding the efficacy and safety of triple oral agents in patients inadequately controlled with dual therapy. In this clinical trial performed in 237 centers in China, 5,535 type 2 diabetic patients inadequately controlled by previous therapies were treated with a stable metformin/sitagliptin dual therapy for 20 weeks. The patients who did not reach the glycated hemoglobin A1c (HbA1c) goal were then further randomized into glimepiride, gliclazide, repaglinide, or acarbose group for an additional 24-week triple therapy. A mean HbA1c reduction of 0.85% was observed when sitagliptin was added to the patients inadequately controlled with metformin in 16 weeks. Further HbA1c reductions in the 24-week triple therapy stage were 0.65% in glimepiride group, 0.70% in gliclazide group, 0.61% in repaglinide group, and 0.45% in acarbose group. The non-inferiority criterion for primary hypotheses was met for gliclazide and repaglinide, but not for acarbose, compared with glimepiride, when added to metformin/sitagliptin dual therapy. The incidences of adverse events (AEs) were 29.2% in the dual therapy stage and 30.3% in the triple therapy stage. Metformin/sitagliptin as baseline therapy, with the addition of a third oral antihyperglycemic agent, including glimepiride, gliclazide, repaglinide, or acarbose, was effective, safe and well-tolerated for achieving an HbA1c <7.0% goal in type 2 diabetic patients inadequately controlled with previous therapies. The timely augmentation of up to three oral antihyperglycemic agents is valid and of important clinical benefit to prevent patients from exposure to unnecessarily prolonged hyperglycemia.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Fosfato de Sitagliptina/uso terapêutico , Acarbose/efeitos adversos , Acarbose/uso terapêutico , Adulto , Glicemia , Carbamatos/efeitos adversos , Carbamatos/uso terapêutico , Quimioterapia Combinada , Feminino , Gliclazida/efeitos adversos , Gliclazida/uso terapêutico , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Masculino , Metformina/efeitos adversos , Pessoa de Meia-Idade , Piperidinas/efeitos adversos , Piperidinas/uso terapêutico , Fosfato de Sitagliptina/efeitos adversos , Compostos de Sulfonilureia/efeitos adversos , Compostos de Sulfonilureia/uso terapêutico , Resultado do TratamentoRESUMO
OBJECTIVE: To perform meta-analyses evaluating the efficacy of adding Liuwei Dihuang Pills (, LDP) to Western medicine in improving treatment outcomes for type 2 diabetes. METHODS: Medline, PubMed, Cochrane Library, and Chinese databases, including the Chinese National Knowledge Infrastructure were searched to identify eligible studies; i.e., if the study involved a randomized clinical trial in which the experimental group combined LDP with Western drugs and the control group used the corresponding Western drugs alone to treat type 2 diabetes. Outcomes were measured in terms of fasting blood glucose (FBG), postprandial blood glucose (2hPG) and HbA1c level. Efficacy was also measured by using control and response rates. The combined odds ratio (OR), mean difference (MD), and 95% confidence intervals (95% CI) were calculated. RESULTS: Studies included in the analysis were less adequate than expected in terms of methodological quality. A total of 1,609 patients from 18 studies were included. We found that adding LDP can lower patients' FBG (MD=0.54 mmol/L, 95% CI [0.15, 0.93], P=0.007), 2hPG (MD=1.05 mmol/L, 95% CI [0.29, 1.81], P<0.01) and HbA1c (MD=0.23, 95% CI [0.02, 0.45], P=0.008). There were also improvements in treatment response rates (OR=3.41, 95% CI [2.38, 4.90], P<0.01) and control rates (OR=2.47, 95% CI [1.91, 3.20], P<0.01). CONCLUSION: Adding LDP to Western medicine might improve treatment outcomes of diabetes, including FBG, 2hPG, response rates and control rates.
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Hipoglicemiantes/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Glicemia/metabolismo , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/sangue , Medicamentos de Ervas Chinesas/efeitos adversos , Jejum/sangue , Gliclazida/efeitos adversos , Gliclazida/uso terapêutico , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Metformina/efeitos adversos , Metformina/uso terapêutico , Viés de Publicação , Resultado do Tratamento , OcidenteRESUMO
AIMS: Sulphonylureas promote insulin release by inhibiting pancreatic potassium channels. Older sulphonylureas such as glyburide (glibenclamide), but not newer ones such as gliclazide, antagonize similar channels in myocardium, interfering with the protective effects of ischaemic preconditioning. Whether this imparts a higher risk of adverse cardiac events is unknown. METHODS: We conducted a population-based cohort study of patients aged 66 years and older who were hospitalized for acute myocardial infarction or who underwent percutaneous coronary intervention between 1 April 2007 and 31 March 2010 while receiving either glyburide or gliclazide. We used a high-dimensional propensity score matching process to ensure similarity of glyburide- and gliclazide-treated patients. The primary outcome was a composite of death or hospitalization for myocardial infarction or heart failure. RESULTS: During the 2-year study period, we matched 1690 patients treated with glyburide to 984 patients treated with gliclazide at the time of hospitalization for acute myocardial infarction or percutaneous coronary intervention. We found no difference in the risk of the composite outcome among patients receiving glyburide (adjusted hazard ratio 1.01; 95% CI 0.86-1.18). We found similar results in secondary analyses of each outcome individually, and in two supplementary analyses (haemorrhage and pneumonia) in which we anticipated no difference between the two patient groups. CONCLUSIONS: Among older patients hospitalized for acute myocardial infarction or percutaneous coronary intervention, treatment with glyburide is not associated with an increased risk of future adverse cardiovascular events relative to gliclazide, suggesting that the effect of glyburide on ischaemic preconditioning is of little clinical relevance.
Assuntos
Angioplastia Coronária com Balão/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Gliclazida/administração & dosagem , Glibureto/administração & dosagem , Infarto do Miocárdio/tratamento farmacológico , Compostos de Sulfonilureia/administração & dosagem , Idoso , Estudos de Coortes , Diabetes Mellitus Tipo 2/mortalidade , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/mortalidade , Angiopatias Diabéticas/fisiopatologia , Feminino , Seguimentos , Gliclazida/efeitos adversos , Glibureto/efeitos adversos , Humanos , Incidência , Precondicionamento Isquêmico , Masculino , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Miocárdio , Ontário/epidemiologia , Fatores de Risco , Compostos de Sulfonilureia/efeitos adversos , Resultado do TratamentoRESUMO
The sulfonylurea gliclazide and the biguanide metformin have different mechanisms to reduce glycemia. We performed a randomized study to compare these two agents with respect to glycemic control and effects on lipid peroxidation markers in 36 adult patients with type 2 diabetes. Both agents significantly decreased glycosylated hemoglobin ([HbA1c] P < .05), fructosamine (P < .05), and the glucose-excursion curve during the oral glucose tolerance test ([OGTT] P < .01). With regard to the insulin curve during this test, no significant change was observed with metformin and a significant increase was measured with gliclazide (P < .05). Considering the small number of events, no significant difference was detected in the number of hypoglycemic episodes between the two agents. More upper-gastrointestinal (GI) symptoms were observed with metformin compared with gliclazide (P < .05). Even with no change in the standard lipid profile, both agents increased serum vitamin E (P < .01 for gliclazide and P < .05 for metformin) and decreased the level of lipid peroxidation markers in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles (P < .05). Despite different mechanisms of action, gliclazide and metformin demonstrated comparable levels of efficacy and complementary effects on lipid peroxidation markers.