澳大利亚悉尼大学Giovanni F M Strippoli团队研究了钠-葡萄糖共转运蛋白2（SGLT-2）抑制剂和胰高血糖素样肽-1（GLP-1）受体激动剂治疗2型糖尿病的效果。2021年1月13日，该研究发表在《英国医学杂志》上。

为了评估钠-葡萄糖共转运蛋白-2（SGLT-2）抑制剂和胰高血糖素样肽-1（GLP-1）受体激动剂治疗伴心血管和肾脏风险的2型糖尿病患者的效果，研究组在Medline、Embase和Cochrane CENTRAL数据库中检索截至2020年8月11日的文献，筛选出比较SGLT-2抑制剂或GLP-1受体激动剂与安慰剂、标准治疗或其他降糖治疗在2型糖尿病成人中的随机对照试验，随访时间为24周或更长时间。

将其汇总后进行随机效应网络荟萃分析，并使用GRADE评估证据的确定性。结果包括对极低风险（无心血管危险因素）、低风险（三个或以上心血管危险因素）、中等风险（心血管疾病）、高风险（慢性肾病）以及非常高的风险（心血管疾病和肾脏疾病）患者5年治疗的每1000名患者的估计绝对疗效。

研究组共纳入764项试验（包括421346名患者）。所有结果均涉及在现有糖尿病治疗中添加SGLT-2抑制剂和GLP-1受体激动剂。这两类药物均降低了全因死亡率、心血管疾病死亡率、非致命性心肌梗塞和肾衰竭率（高确定性证据）。两种药物之间发现了显著差异：SGLT-2抑制剂与比GLP-1受体激动剂相比，避免了更多患者死亡或因心力衰竭入院；而GLP-1受体激动剂与SGLT-2抑制剂相比，避免了更多患者发生非致命性中风。

SGLT-2抑制剂引发生殖器感染（高确定性），而GLP-1受体激动剂则可能引发严重的胃肠道事件（低确定性）。SGLT-2抑制剂和GLP-1受体激动剂可能会降低体重缺乏确定性的证据。几乎没有证明表明SGLT-2抑制剂或GLP-1受体激动剂对截肢、失明、眼病、神经性疼痛或健康相关生活质量有影响。这些药物的绝对益处在不同的患者中有很大的差异，从心血管和肾脏结局的低风险到非常高的风险不等。

总之，对于2型糖尿病患者，SGLT-2抑制剂和GLP-1受体激动剂可降低心血管和肾脏病风险，其利弊也有显著差异。

附：英文原文

Title: Sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials

Author: Suetonia C Palmer, Britta Tendal, Reem A Mustafa, Per Olav Vandvik, Sheyu Li, Qiukui Hao, David Tunnicliffe, Marinella Ruospo, Patrizia Natale, Valeria Saglimbene, Antonio Nicolucci, David W Johnson, Marcello Tonelli, Maria Chiara Rossi, Sunil V Badve, Yeoungjee Cho, Annie-Claire Nadeau-Fredette, Michael Burke, Labib I Faruque, Anita Lloyd, Nasreen Ahmad, Yuanchen Liu, Sophanny Tiv, Tanya Millard, Lucia Gagliardi, Nithin Kolanu, Rahul D Barmanray, Rita McMorrow, Ana Karina Raygoza Cortez, Heath White, Xiangyang Chen, Xu Zhou, Jiali Liu, Andrea Flores Rodríguez, Alejandro Díaz González-Colmenero, Yang Wang, Ling Li, Surya Sutanto, Ricardo Cesar Solis, Fernando Díaz González-Colmenero, René Rodriguez-Gutierrez, Michael Walsh, Gordon Guyatt, Giovanni F M Strippoli

Issue&Volume: 2021/01/13

Abstract:

Objective To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk.

Design Network meta-analysis.

Data sources Medline, Embase, and Cochrane CENTRAL up to 11 August 2020.

Eligibility criteria for selecting studies Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias.

Main outcome measures Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review.

Results 764 trials including 421346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced mortality and admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 5 to 48 fewer deaths in 1000 patients over five years; see interactive decision support tool (https://magicevidence.org/match-it/200820dist/#!/) for all outcomes.

Conclusions In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with notable differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review.

DOI: 10.1136/bmj.m4573

Source: https://www.bmj.com/content/372/bmj.m4573