Schott Gisela, Martinez Yolanda V, Ediriweera de Silva R Erandie, Renom-Guiteras Anna, Vögele Anna, Reeves David, Kunnamo Ilkka, Marttila-Vaara Minna, Sönnichsen Andreas
Drug Commission of the German Medical Association, Berlin, Germany.
NIHR School for Primary Care Research, Manchester Academic Health Science Centre, University of Manchester, Manchester, England.
BMC Geriatr. 2017 Oct 16;17(Suppl 1):226. doi: 10.1186/s12877-017-0571-8.
Preventable drug-related hospital admissions can be associated with drugs used in diabetes and the benefits of strict diabetes control may not outweigh the risks, especially in older populations. The aim of this study was to look for evidence on risks and benefits of DPP-4 inhibitors in older adults and to use this evidence to develop recommendations for the electronic decision support tool of the PRIMA-eDS project.
Systematic review using a staged approach which searches for systematic reviews and meta-analyses first, then individual studies only if prior searches were inconclusive. The target population were older people (≥65 years old) with type 2 diabetes. We included studies reporting on the efficacy and/or safety of DPP-4 inhibitors for the management of type 2 diabetes. Studies were included irrespective of DPP-4 inhibitors prescribed as monotherapy or in combination with any other drug for the treatment of type 2 diabetes. The target intervention was DPP-4 inhibitors compared to placebo, no treatment, other drugs to treat type 2 diabetes or a non-pharmacological intervention.
Thirty studies (reported in 33 publications) were included: 1 meta-analysis, 17 intervention studies and 12 observational studies. Sixteen studies were focused on older adults and 14 studies reported subgroup analyses in participants ≥65, ≥70, or ≥75 years. Comorbidities were reported by 26 studies and frailty or functional status by one study. There were conflicting findings regarding the effectiveness of DPP-4 inhibitors in older adults. In general, DPP-4 inhibitors showed similar or better safety than placebo and other antidiabetic drugs. However, these safety data are mainly based on short-term outcomes like hypoglycaemia in studies with HbA1c control levels recommended for younger people. One recommendation was developed advising clinicians to reconsider the use of DPP-4 inhibitors for the management of type 2 diabetes in older adults with HbA1c <8.5% because of scarce data on clinically relevant benefits of their use. Twenty-two of the included studies were funded by pharmaceutical companies and authored or co-authored by employees of the sponsor.
Other than the surrogate endpoint of improved glycaemic control, data on clinically relevant benefits of DPP-4 inhibitors in the treatment of type 2 diabetes mellitus in older adults is scarce. DPP-4 inhibitors might have a lower risk of hypoglycaemia compared to other antidiabetic drugs but data show conflicting findings for long-term benefits. Further studies are needed that evaluate the risks and benefits of DPP-4 inhibitors for the management of type 2 diabetes mellitus in older adults, using clinically relevant outcomes and including representative samples of older adults with information on their frailty status and comorbidities. Studies are also needed that are independent of pharmaceutical company involvement.
可预防的药物相关住院可能与糖尿病用药有关，严格控制糖尿病的益处可能并不大于风险，尤其是在老年人群中。本研究的目的是寻找有关二肽基肽酶-4（DPP-4）抑制剂在老年人中的风险和益处的证据，并利用这些证据为PRIMA-eDS项目的电子决策支持工具制定建议。
采用分阶段方法进行系统评价，首先检索系统评价和荟萃分析，只有在先期检索无定论时才检索单个研究。目标人群为65岁及以上的2型糖尿病老年人。我们纳入了报告DPP-4抑制剂治疗2型糖尿病的疗效和/或安全性的研究。无论DPP-4抑制剂是作为单一疗法还是与任何其他药物联合用于治疗2型糖尿病，研究均被纳入。目标干预措施是将DPP-4抑制剂与安慰剂、不治疗、其他治疗2型糖尿病的药物或非药物干预措施进行比较。
共纳入30项研究（发表于33篇出版物）：1项荟萃分析、17项干预研究和12项观察性研究。16项研究聚焦于老年人，14项研究报告了65岁及以上、70岁及以上或75岁及以上参与者的亚组分析。26项研究报告了合并症，1项研究报告了虚弱或功能状态。关于DPP-4抑制剂在老年人中的有效性存在相互矛盾的结果。总体而言，DPP-4抑制剂显示出与安慰剂和其他抗糖尿病药物相似或更好的安全性。然而，这些安全性数据主要基于短期结果，如在针对年轻人推荐的糖化血红蛋白（HbA1c）控制水平的研究中的低血糖情况。制定了一项建议，建议临床医生重新考虑在HbA1c<8.5%的老年2型糖尿病患者中使用DPP-4抑制剂，因为关于其使用的临床相关益处的数据稀缺。纳入的研究中有22项由制药公司资助，由赞助商的员工撰写或共同撰写。
除了血糖控制改善这一替代终点外，关于DPP-4抑制剂在老年2型糖尿病治疗中的临床相关益处的数据稀缺。与其他抗糖尿病药物相比，DPP-4抑制剂可能低血糖风险较低，但数据显示其长期益处存在相互矛盾的结果。需要进一步开展研究，以评估DPP-4抑制剂在老年2型糖尿病管理中的风险和益处，采用临床相关结局，并纳入具有虚弱状态和合并症信息的老年代表性样本。还需要开展独立于制药公司参与的研究。
