Metformin: diamonds are forever

Metformin has now been established as the drug of choice for the first-line management of type 2 diabetes mellitus. It reduces insulin resistance, improves glycaemic control, and can be safely combined with other classes of oral hypoglycaemic agents. Equally important, metformin has been shown to have a significant beneficial effect on cardiovascular morbidity. Moreover, this agent acts favourably on blood pressure, lipids, haemostasis and other features of the metabolic syndrome. Metformin also contributes to weight reduction and diabetes prevention.     

二甲双胍治疗不同糖代谢状态肥胖儿童效果评价

【目的】 比较单纯生活方式和加用二甲双胍对肥胖儿童血糖血脂相关指标治疗效果 【方法】 肥胖儿童101例根据OGTT分为组1,糖代谢正常高胰岛素血症组50例,组2,糖代谢异常组51例。组1A单纯生活方式治疗,组1B和组2二甲双胍加生活方式干预治疗1年。 【结果】 组1A治疗前后的体重指数,糖代谢指数,血脂,没有明显的改善(P>0.05)。组1B及组2治疗前后的体重指数,糖代谢指数,血脂,有明显的改善(P<0.01)。 【结论】 二甲双胍加用生活方式的干预优于单纯生活方式的干预。     

Glyburide/metformin tablets: a new therapeutic option for the management of Type 2 diabetes

Oral antidiabetic combination therapy is a proven means of establishing glycaemic control in the hyperglycaemic, Type 2 diabetic patient, but co-administering two oral antidiabetic agents separately may hinder compliance with therapy. A new single-tablet of glyburide/metformin combination therapy (Glucovance^®, Bristol-Myers Squibb, Inc.) has recently been developed, which addresses the primary defects of Type 2 diabetes: β-cell dysfunction and insulin resistance. The glyburide/metformin tablet, taken with meals, is designed to optimise the absorption of glyburide and to address the postprandial glucose rise. Glyburide/metformin tablets are more effective in controlling fasting and postprandial glycaemia than its component monotherapies, at lower doses of metformin and glyburide compared with monotherapy because of the synergy between its glyburide and metformin components. Moreover, a double-blind study showed that glyburide/metformin tablets are more effective than a free combination of glyburide co-administered with metformin in controlling postprandial glucose. Retrospective analyses suggested that glyburide/metformin tablets control glycated haemoglobin (A1C) more effectively than a free combination of glyburide co-administered with metformin, at lower mean doses of glyburide and metformin. The incidence of side effects is lower than separate component therapy for any given A1C. Glyburide/metformin tablets are an effective option for optimising the control of blood glucose in Type 2 diabetic patients and appear to enhance adherence to therapy.     

二甲双胍对糖基化终末产物诱导的成纤维细胞凋亡及相关蛋白caspase-3、Bax及Bcl-2表达的影响

目的探讨晚期糖基化终末产物（AGEs）对原代人皮肤成纤维细胞凋亡的影响,以及二甲双胍（Metformin）对原代皮肤成
纤维细胞凋亡是否存在保护作用。方法取对数生长期的皮肤成纤维细胞,分为空白组,BSA对照组（300 μg/mL）,AGEs刺激组
（100、200、300 μg/mL）,药物组（AGEs 300 μg/mL+Metformin 1 mmol/L）,采用CCK-8检测24、48、72 h细胞凋亡情况;Western
Blot检测细胞培养72 h后凋亡相关蛋白caspase-3、Bax、Bcl-2表达情况。结果CCK-8结果显示AGEs诱导皮肤成纤维细胞凋
亡呈浓度及时间依赖性,AGEs 300 μg/mL诱导72 h后可见细胞凋亡明显增多（0.72±0.02 vs 1±0.04,P<0.05）,加入二甲双胍后可
对成纤维细胞起一定保护作用（0.98±0.02 vs 0.72±0.02,P<0.05）。Western Blot显示AGEs 300 μg/mL刺激成纤维细胞72 h后,
caspase-3、Bax 蛋白表达增加（P<0.05）,而Bcl-2 蛋白表达下降（P<0.05）,Bcl-2/Bax 比值下降（P<0.05）,二甲双胍作用后
caspase-3、Bax蛋白表达水平较刺激组明显下降（P<0.05）,而Bcl-2及Bcl-2/Bax比值则明显上升（P<0.05）。结论AGEs可诱导
人皮肤成纤维细胞凋亡增加,二甲双胍可以通过调控caspase-3、Bax及Bcl-2表达,从而起到抗凋亡作用。
     

Metformin‐associated risk of acute dialysis in patients with type 2 diabetes: A nationwide cohort study

Recent guidelines governing anti‐diabetic medications increasingly advocate metformin as first‐line therapy in all patients with type 2 diabetes. However, metformin could be associated with increased risk of acute kidney injury (AKI), acute dialysis and lactate acidosis in marginal patients. In a retrospective nationwide cohort study, a total of 168 443 drug‐naïve patients with type 2 diabetes ≥50 years, initiating treatment with either metformin or sulphonyl in Denmark between 2000 and 2012 were included in this study (70.7% initiated treatment with metformin); calculation of 1‐year risk of acute dialysis was based on g‐standardization of cause‐specific Cox regression models for acute dialysis, end‐stage renal disease and death. One‐year risks of acute dialysis were 92.4 per 100 000 (95% CI, 67.1‐121.3) and 142.7 per 100 000 (95% CI, 118.3‐168.0) for sulphonylurea and metformin, respectively. The metformin‐associated 1‐year risk of acute dialysis was increased by 50.3 per 100 000 (95% CI, 7.9‐88.6), corresponding to a risk ratio of 1.53 (95% CI, 1.06‐2.23), and a number needed to harm of 1988, thus providing evidence of potential concerns pertaining to the increasing use of metformin.