Johnson J L, Wolf S L, Kabadi U M
Carl T. Hayden Veterans Affairs Medical Center, Tucson, USA.
Arch Intern Med. 1996 Feb 12;156(3):259-64.
Numerous studies demonstrate the efficacy of the combination therapy of insulin and sulfonylurea in subjects with type II diabetes mellitus. However, two recent meta-analyses of randomized trials during the last decade provided inconsistent conclusions and failed to resolve the controversy.
To assess the efficacy of insulin and sulfonylurea combination therapy in type II diabetes mellitus by performing meta-analysis of only the controlled studies selected according to specific strict criteria.
A computerized literature survey was conducted using the MEDLINE database from January 1980 through March 1992 with the search headings of "sulfonylurea" and "insulin" and "combination therapy in diabetes mellitus. "A manual search was also performed using references from each retrieved report. Case reports, review articles, editorials, and citations reported in non-English-language journals without English translations were excluded. Forty-three citations were obtained. Four strict inclusion criteria were used to select studies: randomized, placebo-controlled trials (oral agent plus insulin vs placebo plus insulin); homogeneous target population (subjects with type II diabetes); intervention using the same sulfonylurea agent in a combination therapy; and uniform outcome measures to evaluate efficacy such as body weight; values for serum glucose, glycohemoglobin, and C peptide; daily insulin dosage; and lipid concentrations. More stringent qualitative subcriteria were then used to eliminate bias in the final unanimous selection by two blinded reviewers. Data were pooled and analyzed using Student's t test and Winer's combined test.
Sixteen studies satisfied the inclusion criteria. Metabolic control improved with the combination therapy as reflected by a significant lowering of fasting serum glucose values (P < .01) and glycohemoglobin concentrations (P < .025). Moreover, improved metabolic control was achieved with a significantly smaller daily insulin dose (P < .01) and without a significant change in body weight. Finally, the combination therapy enhanced the endogenous insulin secretion as expressed by an increase in fasting serum C peptide concentration (P < .05).
Combination therapy with insulin and sulfonylurea may be a more appropriate and a suitable option to insulin monotherapy in subjects with non-insulin-dependent diabetes in whom primary or secondary failure to sulfonylurea developed. It may also be a more cost-effective way of long-term management in this group of subjects, especially in the elderly.
大量研究证明胰岛素与磺脲类药物联合治疗对II型糖尿病患者有效。然而，最近对过去十年随机试验的两项荟萃分析得出了不一致的结论，未能解决这一争议。
通过仅对根据特定严格标准选择的对照研究进行荟萃分析，评估胰岛素与磺脲类药物联合治疗II型糖尿病的疗效。
使用MEDLINE数据库从1980年1月至1992年3月进行计算机文献检索，检索词为“磺脲类药物”、“胰岛素”和“糖尿病联合治疗”。还使用每份检索报告中的参考文献进行了手工检索。排除病例报告、综述文章、社论以及非英文期刊报道且无英文译文的文献。共获得43条引用文献。采用四条严格的纳入标准选择研究：随机、安慰剂对照试验（口服药物加胰岛素对比安慰剂加胰岛素）；同质目标人群（II型糖尿病患者）；联合治疗中使用相同的磺脲类药物；采用统一的疗效评估指标，如体重、血糖值、糖化血红蛋白和C肽值、每日胰岛素剂量以及血脂浓度。然后使用更严格的定性子标准消除两名盲法评审员最终一致选择中的偏差。采用学生t检验和维纳联合检验对数据进行汇总和分析。
16项研究符合纳入标准。联合治疗改善了代谢控制，空腹血糖值显著降低（P < 0.01）以及糖化血红蛋白浓度显著降低（P < 0.025）反映了这一点。此外，每日胰岛素剂量显著降低（P < 0.01）且体重无显著变化的情况下实现了代谢控制的改善。最后，联合治疗通过空腹血清C肽浓度升高（P < 0.05）表明内源性胰岛素分泌增加。
对于出现磺脲类药物原发性或继发性失效的非胰岛素依赖型糖尿病患者，胰岛素与磺脲类药物联合治疗可能是比胰岛素单一疗法更合适的选择。对于这组患者，尤其是老年患者，它也可能是一种更具成本效益的长期管理方式。
