Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus - Progressive requirement for multiple therapies (UKPDS 49)
Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus - Progressive requirement for multiple therapies (UKPDS 49)
复制标题
DOI：
10.1001/jama.281.21.2005
复制
发表时间：
1999-06-02
影响因子：
120.7
通讯作者：
Holman, RR
中科院分区：
文献类型：
--
作者：
Turner, RC;Cull, CA;Holman, RR
背景单纯饮食、胰岛素、磺脲或二甲双胍可改善2型糖尿病患者的血糖，但哪种治疗最常达到目标空腹血糖浓度低于7.8 mmol/L(140 mg/dL)或糖化血红蛋白A(1c)(HbA(1c))低于7%尚不清楚。目的评估每种治疗方法达到美国糖尿病协会设定的血糖控制目标水平的频率。新诊断的2型糖尿病患者4075例，年龄25~65岁，空腹血糖中位数11.5(9.0~14.4)mmol/L[207(162~259)mg/dL]，糖化血红蛋白(1c)9.1%(7.5%~10.7%)，在低脂肪、高碳水化合物、高纤维饮食的干预3个月后，患者被随机分为单纯饮食、胰岛素、磺脲类或二甲双胍治疗。主要观察指标为空腹血糖和糖化血红蛋白(1c)水平，以及在诊断后3、6或9年达到目标水平低于7%HbA(1c)或低于7.8mmoL/L(140 mg/dL)空腹血糖的患者比例。在饮食、胰岛素或磺脲类药物治疗9年后，分别有8%、42%和24%的患者空腹血糖水平低于7.8 mmol/L(140 mg/dL)，9%、28%和24%的患者HbA(1c)水平低于7%。在随机服用二甲双胍的肥胖症患者中，18%的患者空腹血糖低于7.8 mmol/L(140 mg/dL)，13%的患者糖化血红蛋白(1c)水平低于7%。不太可能达到目标水平的患者比其他患者更年轻、更肥胖或更高血糖。结论每种治疗药物作为单一疗法，与单独饮食相比，达到HBA(1c)低于7%的患者比例增加了2-3倍。然而，糖尿病控制的逐渐恶化是这样的，在3年后，大约50%的患者可以通过单一疗法达到这一目标，到9年，这一比例下降到大约25%。大多数患者需要多种疗法才能在较长时间内达到这些血糖目标水平。
Context Treatment with diet alone, insulin, sulfonylurea, or metformin is known to improve glycemia in patients with type 2 diabetes mellitus, but which treatment most frequently attains target fasting plasma glucose (FPG) concentration of less than 7.8 mmol/L (140 mg/dL) or glycosylated hemoglobin A(1c) (HbA(1c)) below 7% is unknown.Objective To assess how often each therapy can achieve the glycemic control target levels set by the American Diabetes Association.Design Randomized controlled trial conducted between 1977 and 1997. Patients were recruited between 1977 and 1991 and were followed up every 3 months for 3, 6, and 9 years after enrollment.Setting Outpatient diabetes clinics in 15 UK hospitals.Patients A total of 4075 patients newly diagnosed as having type 2 diabetes ranged in age between 25 and 65 years and had a median (interquartile range) FPG concentration of 11.5 (9.0-14.4) mmol/L [207 (162-259) mg/dL], HbA(1c) levels of 9.1% (7.5%-10.7%), and a mean (SD) body mass index of 29 (6) kg/m(2).Interventions After 3 months on a low-fat, high-carbohydrate, high-fiber diet, patients were randomized to therapy with diet alone, insulin, sulfonylurea, or metformin.Main Outcome Measures Fasting plasma glucose and HbA(1c) levels, and the proportion of patients who achieved target levels below 7% HbA(1c) or less than 7.8 mmol/L (140 mg/dL) FPG at 3, 6, or 9 years following diagnosis.Results The proportion of patients who maintained target glycemic levels declined markedly over 9 years of follow-up. After 9 years of monotherapy with diet, insulin, or sulfonylurea, 8%, 42%, and 24%, respectively, achieved FPG levels of less than 7.8 mmol/L (140 mg/dL) and 9%, 28%, and 24% achieved HbA(1c) levels below 7%. In obese patients randomized to metformin, 18% attained FPG levels of less than 7.8 mmol/L (140 mg/dL) and 13% attained HbA(1c) levels below 7%. Patients less likely to achieve target levels were younger, more obese, or more hyperglycemic than other patients.Conclusions Each therapeutic agent, as monotherapy, increased 2- to 3-fold the proportion of patients who attained HbA(1c) below 7% compared with diet alone. However, the progressive deterioration of diabetes control was such that after 3 years approximately 50% of patients could attain this goal with monotherapy, and by 9 years this declined to approximately 25%. The majority of patients need multiple therapies to attain these glycemic target levels in the longer term.