Asmal A C, Marble A
Drugs. 1984 Jul;28(1):62-78. doi: 10.2165/00003495-198428010-00004.
Despite the availability of oral hypoglycaemic agents for nearly 30 years, their precise mode of action and role in the management of diabetes mellitus remains poorly defined and controversial. They are regarded by many, though not all, clinicians as helpful adjuncts in the treatment of patients with non-insulin-dependent diabetes who have failed to respond satisfactorily to an adequate programme of dietary treatment. Their initial effectiveness is greatest in those patients who have had diabetes for less than 5 years, are overweight at the time of initiation of therapy, and whose fasting blood glucose levels are not unduly raised (less than 200 mg/dl). If they are receiving treatment with insulin and a shift to oral compounds is contemplated, success in the changeover is more likely if the daily dose has been less than 20 to 30 units daily. While their efficacy in maintaining adequate glycaemic control over the short term in responsive patients is unquestioned, the long term benefit of oral hypoglycaemic agents in reducing morbidity and mortality of late complications remains to be substantiated. In this regard, where long term efficacy is difficult to quantify, physician vigilance for chronic toxicity assumes a special importance. Notwithstanding the potential for interaction between sulphonylureas and numerous other drugs, significant adverse effects are uncommon. Hypoglycaemia is the major health concern associated with the use of sulphonylureas, and lactic acidosis has been the major problem with biguanides. Careful patient selection is thus the key to ensuring efficacy and avoiding toxicity. Recent evidence suggests that while the insulinotropic action of the sulphonylureas may explain the short term hypoglycaemic effect of these compounds, their reported action in enhancing insulin sensitivity, both at the receptor and post-receptor levels, more likely accounts for the long term maintenance of improved carbohydrate tolerance. The relatively new ('second generation') sulphonylurea compounds have not been shown to possess clearly defined advantages over the older preparations; the potentially beneficial effects of gliclazide on the microangiopathic changes of diabetes require considerable further evaluation.
尽管口服降糖药已问世近30年，但其确切的作用方式以及在糖尿病管理中的作用仍不清楚且存在争议。许多（并非所有）临床医生认为，对于非胰岛素依赖型糖尿病患者，在饮食治疗方案效果不佳时，口服降糖药是有用的辅助治疗手段。对于糖尿病病程少于5年、开始治疗时超重且空腹血糖水平没有过度升高（低于200mg/dl）的患者，口服降糖药的初始疗效最佳。如果患者正在接受胰岛素治疗且考虑改用口服降糖药，若每日胰岛素剂量小于20至30单位，换药成功的可能性更大。虽然口服降糖药在短期内对有反应的患者维持血糖良好控制的疗效是毋庸置疑的，但口服降糖药在降低晚期并发症的发病率和死亡率方面的长期益处仍有待证实。在这方面，由于长期疗效难以量化，医生对慢性毒性的警惕就显得尤为重要。尽管磺脲类药物与许多其他药物之间存在相互作用的可能性，但严重不良反应并不常见。低血糖是使用磺脲类药物主要的健康问题，而乳酸酸中毒一直是双胍类药物的主要问题。因此，谨慎选择患者是确保疗效和避免毒性的关键。最近的证据表明，虽然磺脲类药物的促胰岛素分泌作用可能解释了这些化合物的短期降糖作用，但它们在受体水平和受体后水平增强胰岛素敏感性的作用，更有可能是碳水化合物耐受性长期改善得以维持的原因。相对较新的（“第二代”）磺脲类化合物并未显示出比旧制剂有明确的优势；格列齐特对糖尿病微血管病变的潜在有益作用需要进一步大量评估。
