Schwartz Sherwyn L
Cetero Research, San Antonio, Texas, USA.
Am J Geriatr Pharmacother. 2010 Oct;8(5):405-18. doi: 10.1016/j.amjopharm.2010.10.003.
Achievement of glycemic control in elderly patients with type 2 diabetes mellitus (DM) is complicated by many factors.
The aim of this article was to systematically review evidence on the effectiveness of dipeptidyl peptidase-4 (DPP-4) inhibitors (ie, lowering of glycosylated hemoglobin [HbA(1c)]), the risk of hypoglycemia associated with these agents, and the effects of these agents on body weight in elderly patients with type 2 DM.
The PubMed and Biosis databases were searched for reports of clinical trials and meeting presentations (eg, abstracts, posters) published in English between January 1, 2000, and October 25, 2009, that included elderly patients with type 2 DM who were treated with sitagliptin, saxagliptin, vildagliptin, alogliptin, BI-1356, DSP-7238, or PF-734200. Pharmacokinetic and pharmacodynamic studies were excluded from the review, as were studies that did not specifically provide quantitative clinical data on glycemic parameters or specifically list patients aged ≥65 years.
Eighty-five articles and 5 presentations were identified in the search; of those, 18 articles and 3 presentations were included in the review. These publications described studies of DPP-4 inhibitors administered as monotherapy or in combination with metformin, a thiazolidinedione, glimepiride, glibenclamide, or insulin. Quantitative data indicated that, in these elderly patients (generally defined as ≥65 years of age) with type 2 DM, DPP-4 inhibitors were associated with significant HbA(1c) reductions that ranged from ~0.7% (baseline HbA(1c) = 7.8%; P < 0.001) to 1.2% (baseline HbA(1c) = 8.3%; P < 0.05). Additional studies that did not quantify the number of elderly patients (as would a subanalysis), but did specify that elderly patients were included and that patient age did not influence the results, were incorporated in this review to support the quantitative results. No significant differences were noted in the HbA(1c)-lowering effects of these agents between elderly and younger patients. Less information about the incidence of hypoglycemia or weight gain in elderly patients was reported, but the available results suggested that the risk of hypoglycemia with DPP-4 inhibitors was not significantly different from that with placebo (sitagliptin 50 or 100 mg/d [0%] vs placebo [0%]; saxagliptin 5 mg/d [6.3%] vs placebo [8.0%]; vildagliptin 100 mg/d [2.32 events per patient-year] vs placebo [2.64 events per patient-year]; alogliptin 12.5 mg/d [8.0%] vs placebo [10.5%]) and that these agents were weight neutral (change, ≤0.9 kg).
For elderly patients with type 2 DM, reductions in HbA(1c) after treatment with a DPP-4 inhibitor were not significantly different from those in younger patients. Use of DPP-4 inhibitors in these studies was associated with a low risk of hypoglycemia, and these agents were weight neutral.
老年2型糖尿病患者实现血糖控制受多种因素影响。
本文旨在系统回顾二肽基肽酶-4（DPP-4）抑制剂在老年2型糖尿病患者中的有效性（即糖化血红蛋白[HbA(1c)]降低情况）、与这些药物相关的低血糖风险以及这些药物对体重的影响的证据。
检索PubMed和Biosis数据库，查找2000年1月1日至2009年10月25日期间以英文发表的临床试验报告和会议发言（如摘要、海报），这些研究纳入了接受西他列汀、沙格列汀、维格列汀、阿格列汀、BI-1356、DSP-7238或PF-734200治疗的老年2型糖尿病患者。药代动力学和药效学研究被排除在本综述之外，未专门提供血糖参数定量临床数据或未明确列出年龄≥65岁患者的研究也被排除。
检索到85篇文章和5个发言；其中，纳入本综述的有18篇文章和3个发言。这些出版物描述了DPP-4抑制剂作为单一疗法或与二甲双胍、噻唑烷二酮类、格列美脲、格列本脲或胰岛素联合使用的研究。定量数据表明，在这些老年（一般定义为≥65岁）2型糖尿病患者中，DPP-4抑制剂可使HbA(1c)显著降低，降幅在~0.7%（基线HbA(1c)=7.8%；P<0.001）至1.2%（基线HbA(1c)=8.3%；P<0.05）之间。本综述纳入了其他未对老年患者数量进行定量分析（如亚组分析那样），但明确纳入了老年患者且患者年龄不影响结果的研究，以支持定量结果。老年患者与年轻患者在这些药物降低HbA(1c)的效果上未观察到显著差异。关于老年患者低血糖发生率或体重增加的信息报道较少，但现有结果表明，DPP-4抑制剂导致低血糖的风险与安慰剂无显著差异（西他列汀50或100mg/d[0%]对比安慰剂[0%]；沙格列汀5mg/d[6.3%]对比安慰剂[8.0%]；维格列汀100mg/d[每位患者每年2.32次事件]对比安慰剂[每位患者每年2.64次事件]；阿格列汀12.5mg/d[8.日对比安慰剂[日]），且这些药物对体重无影响（变化≤0.9kg）。
对于老年2型糖尿病患者，DPP-4抑制剂治疗后HbA(1c)的降低与年轻患者无显著差异。这些研究中使用DPP-4抑制剂导致低血糖的风险较低，且这些药物对体重无影响。
