Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)
Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)
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DOI：
10.1016/s0140-6736(98)07037-8
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发表时间：
1998-09-12
期刊：
影响因子：
168.9
通讯作者：
Hadden, D
中科院分区：
文献类型：
--
作者：
Turner, RC;Holman, RR;Hadden, D
背景：在2型糖尿病患者中，胰岛素或磺脲类药物强化血糖控制可减少微血管疾病的进展，还可降低心脏病发作的风险。方法在15个中心的4075例患者中，1704例超重(理想体重120%)的新诊断的2型糖尿病患者，平均年龄53岁，在3个月的初始饮食后空腹血糖(FPG；6.1-15.0 mmol/L)升高，无高血糖症状。753例纳入随机对照试验，中位持续时间为10.7年，主要采用常规饮食策略(n=411)和强化血糖控制策略(目标为空腹血糖<6 mm ol/L)(n=342)。二次分析比较了342名服用二甲双胍的患者和951名接受强化血糖控制的超重患者，氯丙胺(n=265)、格列本脲(n=277)或胰岛素(n=409)。主要结果衡量指标是任何糖尿病相关临床终点、糖尿病相关死亡和全因死亡率的总和。在一项补充的随机对照试验中，537名非超重和超重的患者，平均年龄59岁，已经接受最大剂量磺脲类药物治疗，但空腹血糖升高(6.1-15.0 mmol/L)，被分配到继续接受磺脲类药物治疗(n=269)或加用二甲双胍(n=268)。结果发现，二甲双胍组糖化血红蛋白(HbA(1c))的中位数为7.4%，而常规组为8.0%。与常规治疗组相比，服用二甲双胍的患者糖尿病相关终点风险降低32%(95%可信区间13-47，p=0.002)，糖尿病相关死亡风险降低42%(9-63，p=0.017)，全因死亡率降低36%(9-55，p=0.011)。在接受强化血糖控制的患者中，二甲双胍在糖尿病相关终点(p=0.0034)、全因死亡率(p=0.021)和中风(p=0.032)方面显示出比氯丙胺、格列本脲或胰岛素更大的效果。在接受磺酰尿素治疗的患者中，早期使用二甲双胍与糖尿病相关死亡的风险增加有关(与继续使用磺脲类药物相比，风险增加96%[95%可信区间2-275]，p=0.039)。对主要研究和补充研究的综合分析表明，服用二甲双胍的糖尿病相关终点患者较少(风险降低19%[2-33]，p=0.033)。在4416名患者中，对糖尿病相关原因死亡与同时治疗糖尿病的可能相关性的流行病学评估没有显示磺脲类药物和二甲双胍联合治疗的患者糖尿病相关死亡的风险没有增加(风险降低5%[-33至32]，p=0.78)。解释由于二甲双胍强化血糖控制似乎可以降低超重糖尿病患者糖尿病相关终点的风险，并且与胰岛素和磺脲类药物相比，它与体重增加和低血糖发作较少相关，因此它可能是这些患者的一线药物治疗选择。
Background In patients with type 2 diabetes, intensive blood-glucose control with insulin or sulphonylurea therapy decreases progression of microvascular disease and may also reduce the risk of heart attacks. This study investigated whether intensive glucose control with metformin has any specific advantage or disadvantage.Methods Of 4075 patients recruited to UKPDS in 15 centres, 1704 overweight (>120% ideal bodyweight) patients with newly diagnosed type 2 diabetes, mean age 53 years, had raised fasting plasma glucose (FPG; 6.1-15.0 mmol/L) without hyperglycaemic symptoms after 3 months' initial diet. 753 were included in a randomised controlled trial, median duration 10.7 years, of conventional policy, primarily with diet alone (n=411) versus intensive blood-glucose control policy with metformin, aiming for FPG below 6 mmol/L (n=342). A secondary analysis compared the 342 patients allocated metformin with 951 overweight patients allocated intensive blood-glucose control with chlorpropamide (n=265), glibenclamide (n=277), or insulin (n=409). The primary outcome measures were aggregates of any diabetes-related clinical endpoint, diabetes-related death, and all-cause mortality. In a supplementary randomised controlled trial, 537 non-overweight and overweight patients, mean age 59 years, who were already on maximum sulphonylurea therapy but had raised FPG (6.1-15.0 mmol/L), were allocated continuing sulphonylurea therapy alone (n=269) or addition of metformin (n=268).Findings Median glycated haemoglobin (HbA(1c)) was 7.4% in the metformin group compared with 8.0% in the conventional group. Patients allocated metformin, compared with the conventional group, had risk reductions of 32% (95% CI 13-47, p=0.002) for any diabetes-related endpoint, 42% for diabetes-related death (9-63, p=0.017), and 36% for all-cause mortality (9-55, p=0.011). Among patients allocated intensive blood-glucose control, metformin showed a greater effect than chlorpropamide, glibenclamide, or insulin for any diabetes-related endpoint (p=0.0034), all-cause mortality (p=0.021), and stroke (p=0.032). Early addition of metformin in sulphonyl urea-treated patients was associated with an increased risk of diabetes-related death (96% increased risk [95% CI 2-275], p=0.039) compared with continued sulphonylurea alone. A combined analysis of the main and supplementary studies showed fewer metformin-allocated patients having diabetes-related endpoints (risk reduction 19% [2-33], p=0.033). Epidemiological assessment of the possible association of death from diabetes-related causes with the concurrent therapy of diabetes in 4416 patients did not show an increased risk in diabetes-related death in patients treated with a combination of sulphonylurea and metformin (risk reduction 5% [-33 to 32], p=0.78).Interpretation Since intensive glucose control with metformin appears to decrease the risk of diabetes-related endpoints in overweight diabetic patients, and is associated with less weight gain and fewer hypoglycaemic attacks than are insulin and sulphonylureas, it may be the first-line pharmacological therapy of choice in these patients.