Diabetes treatments and risk of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia: open cohort study in primary care
Diabetes treatments and risk of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia: open cohort study in primary care
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DOI：
10.1136/bmj.i1450
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发表时间：
2016-03-30
影响因子：
105.7
通讯作者：
Coupland, Carol
中科院分区：
文献类型：
--
作者：
Hippisley-Cox, Julia;Coupland, Carol
目的评估与处方糖尿病药物相关的2型糖尿病患者截肢、失明、严重肾衰竭、高血糖和低血糖的风险，特别是包括格列汀类或格列酮类的新药剂研究对象：469688例年龄在25- 30岁的2型糖尿病患者，2007年4月1日至2015年1月31日期间年满84岁。暴露降血糖药物（格列酮、格列汀类、二甲双胍、磺脲类、胰岛素等）单独使用和联合使用。主要结果测量首先记录截肢、失明、严重肾衰竭、高血糖和低血糖的诊断，记录在患者的初级保健、死亡率或医院记录中。考克斯模型估计糖尿病治疗的风险比，调整潜在的混杂因素。在随访期间，分别有21 308（4.5%）和32 533（6.9%）例患者接受格列酮和格列汀类药物处方。与不使用格列酮相比，（调整后的风险比为0.71，95%置信区间为0.57 - 0.89;发生率为14.4/10000人年暴露）和低血糖风险增加（1.22，1.10 - 1.37; 65.1）;格列汀类与低血糖风险降低相关（0.86，0.77 - 0.96; 45.8）。尽管接受格列酮单药治疗或格列酮类单药治疗的患者数量相对较少，但与二甲双胍单药治疗相比，重度肾衰竭的风险显著增加（校正风险比2.55，95%置信区间1.13 - 5.74）。我们发现，与二甲双胍单药治疗相比，二甲双胍与格列汀（0.78，0.62 - 0.97）或格列酮（0.60，0.45 - 0.80）联合治疗的患者发生高血糖症的风险显著降低。患者接受二甲双胍、磺脲类药物和格列汀类药物三联治疗（校正风险比5.07，95%置信区间4.28 - 6.00）或格列酮（6.32，5.35 - 7.45）的低血糖风险显著高于二甲双胍单药治疗，但这些风险与二甲双胍和磺脲类药物双重治疗的风险相似（6.03，5.47至6.63）。与二甲双胍单药治疗（0.67，0.48至0.94）相比，二甲双胍、磺脲类和格列酮三联治疗的患者失明风险显著降低。CONCLUSIONSWe发现，与二甲双胍单药治疗相比，二甲双胍与格列汀类或格列酮三联治疗的患者高血糖风险较低。与二甲双胍单药治疗相比，二甲双胍、磺脲类药物和格列汀类或格列酮三联治疗与低血糖风险增加相关，这与二甲双胍和磺脲类药物双联治疗的风险相似。与二甲双胍单药治疗相比，二甲双胍、磺脲类和格列酮三联治疗与失明风险降低相关。这些结果，虽然受到残余混杂，可能有影响的处方降血糖药物。
OBJECTIVETo assess the risks of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia in patients with type 2 diabetes associated with prescribed diabetes drugs, particularly newer agents including gliptins or glitazones (thiazolidinediones).DESIGNOpen cohort study in primary care.SETTING1243 practices contributing data to the QResearch database in England.PARTICIPANTS469 688 patients with type 2 diabetes aged 25-84 years between 1 April 2007 and 31 January 2015.EXPOSURESHypoglycaemic agents (glitazones, gliptins, metformin, sulphonylureas, insulin, and other) alone and in combination.MAIN OUTCOME MEASURESFirst recorded diagnoses of amputation, blindness, severe kidney failure, hyperglycaemia, and hypoglycaemia recorded on patients' primary care, mortality, or hospital records. Cox models estimated hazard ratios for diabetes treatments adjusting for potential confounders.RESULTS21 308 (4.5%) and 32 533 (6.9%) patients received prescriptions for glitazones and gliptins during follow-up, respectively. Compared with non-use, glitazones were associated with a decreased risk of blindness (adjusted hazard ratio 0.71, 95% confidence interval 0.57 to 0.89; rate 14.4 per 10 000 person years of exposure) and an increased risk of hypoglycaemia (1.22, 1.10 to 1.37; 65.1); gliptins were associated with a decreased risk of hypoglycaemia (0.86, 0.77 to 0.96; 45.8). Although the numbers of patients prescribed gliptin monotherapy or glitazones monotherapy were relatively low, there were significantly increased risks of severe kidney failure compared with metformin monotherapy (adjusted hazard ratio 2.55, 95% confidence interval 1.13 to 5.74). We found significantly lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins (0.78, 0.62 to 0.97) or glitazones (0.60, 0.45 to 0.80) compared with metformin monotherapy. Patients prescribed triple therapy with metformin, sulphonylureas, and either gliptins (adjusted hazard ratio 5.07, 95% confidence interval 4.28 to 6.00) or glitazones (6.32, 5.35 to 7.45) had significantly higher risks of hypoglycaemia than those prescribed metformin monotherapy, but these risks were similar to those involving dual therapy with metformin and sulphonylureas (6.03, 5.47 to 6.63). Patients prescribed triple therapy with metformin, sulphonylureas, and glitazones had a significantly reduced risk of blindness compared with metformin monotherapy (0.67, 0.48 to 0.94).CONCLUSIONSWe have found lower risks of hyperglycaemia among patients prescribed dual therapy involving metformin with either gliptins or glitazones compared with metformin alone. Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and either gliptins or glitazones was associated with an increased risk of hypoglycaemia, which was similar to the risk for dual therapy with metformin and sulphonylureas. Compared with metformin monotherapy, triple therapy with metformin, sulphonylureas, and glitazones was associated with a reduced risk of blindness. These results, while subject to residual confounding, could have implications for the prescribing of hypoglycaemic drugs.