胰高血糖素样肽-1 受体激动剂的长期获益和危害：系统评价和荟萃分析。
The Longer-Term Benefits and Harms of Glucagon-Like Peptide-1 Receptor Agonists: a Systematic Review and Meta-Analysis.
机构信息
Department of Medicine, University of Chicago, Chicago, IL, USA.
Centre for Health Economics and Policy Innovation, Imperial College Business School, London, UK.
出版信息
J Gen Intern Med. 2022 Feb;37(2):415-438. doi: 10.1007/s11606-021-07105-9. Epub 2021 Sep 10.
BACKGROUND
Previous meta-analyses of the benefits and harms of glucagon-like peptide-1 receptor agonists (GLP1RAs) have been limited to specific outcomes and comparisons and often included short-term results. We aimed to estimate the longer-term effects of GLP1RAs on cardiovascular risk factors, microvascular and macrovascular complications, mortality, and adverse events in patients with type 2 diabetes, compared to placebo and other anti-hyperglycemic medications.
METHODS
We searched PubMed, Scopus, and clinicaltrials.gov (inception-July 2019) for randomized controlled trials ≥ 52 weeks' duration that compared a GLP1RA to placebo or other anti-hyperglycemic medication and included at least one outcome of interest. Outcomes included cardiovascular risk factors, microvascular and macrovascular complications, all-cause mortality, and treatment-related adverse events. We performed random effects meta-analyses to give summary estimates using weighted mean differences (MD) and pooled relative risks (RR). Risk of bias was assessed using the Cochrane Collaboration risk of bias in randomized trials tool. Quality of evidence was summarized using the Grading of Recommendations, Assessment, Development, and Evaluation approach. The study was registered a priori with PROSPERO (CRD42018090506).
RESULTS
Forty-five trials with a mean duration of 1.7 years comprising 71,517 patients were included. Compared to placebo, GLP1RAs reduced cardiovascular risk factors, microvascular complications (including renal events, RR 0.85, 0.80-0.90), macrovascular complications (including stroke, RR 0.86, 0.78-0.95), and mortality (RR 0.89, 0.84-0.94). Compared to other anti-hyperglycemic medications, GLP1RAs only reduced cardiovascular risk factors. Increased gastrointestinal events causing treatment discontinuation were observed in both comparisons.
DISCUSSION
GLP1RAs reduced cardiovascular risk factors and increased gastrointestinal events compared to placebo and other anti-hyperglycemic medications. GLP1RAs also reduced MACE, stroke, renal events, and mortality in comparisons with placebo; however, analyses were inconclusive for comparisons with other anti-hyperglycemic medications. Given the high costs of GLP1RAs, the lack of long-term evidence comparing GLP1RAs to other anti-hyperglycemic medications has significant policy and clinical practice implications.
背景
先前关于胰高血糖素样肽-1 受体激动剂（GLP1RAs）的益处和危害的荟萃分析仅限于特定的结局和比较，且通常纳入了短期结果。我们旨在评估 GLP1RAs 与安慰剂和其他抗高血糖药物相比，在 2 型糖尿病患者中对心血管危险因素、微血管和大血管并发症、死亡率和不良事件的长期影响。
方法
我们在 PubMed、Scopus 和 clinicaltrials.gov（从创建到 2019 年 7 月）中检索了持续时间至少为 52 周的随机对照试验，这些试验比较了 GLP1RA 与安慰剂或其他抗高血糖药物，并纳入了至少一项感兴趣的结局。结局包括心血管危险因素、微血管和大血管并发症、全因死亡率和与治疗相关的不良事件。我们使用加权均数差（MD）和汇总相对风险（RR）进行随机效应荟萃分析，以给出汇总估计值。使用 Cochrane 协作组随机试验偏倚风险工具评估偏倚风险。使用推荐评估、制定与评价（GRADE）方法总结证据质量。该研究在 PROSPERO（CRD42018090506）预先进行了登记。
结果
纳入了 45 项平均持续时间为 1.7 年、包含 71517 例患者的试验。与安慰剂相比，GLP1RAs 降低了心血管危险因素、微血管并发症（包括肾脏事件，RR 0.85，0.80-0.90）、大血管并发症（包括中风，RR 0.86，0.78-0.95）和死亡率（RR 0.89，0.84-0.94）。与其他抗高血糖药物相比，GLP1RAs 仅降低了心血管危险因素。在这两种比较中均观察到因胃肠道事件导致治疗中断的增加。
讨论
与安慰剂和其他抗高血糖药物相比，GLP1RAs 降低了心血管危险因素并增加了胃肠道事件。GLP1RAs 还降低了与安慰剂相比的 MACE、中风、肾脏事件和死亡率；然而，与其他抗高血糖药物相比，分析结果尚无定论。鉴于 GLP1RAs 的高成本，缺乏长期证据比较 GLP1RAs 与其他抗高血糖药物对政策和临床实践有重大影响。
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