SGLT-2抑制劑和GLP-1受體激動劑可降低2型糖尿病患者的心血管和腎臟病風險
作者：
小柯機器人發布時間：2021/1/17 16:12:02
澳大利亞雪梨大學Giovanni F M Strippoli團隊研究了鈉-葡萄糖共轉運蛋白2（SGLT-2）抑制劑和胰高血糖素樣肽-1（GLP-1）受體激動劑治療2型糖尿病的效果。2021年1月13日，該研究發表在《英國醫學雜誌》上。
為了評估鈉-葡萄糖共轉運蛋白-2（SGLT-2）抑制劑和胰高血糖素樣肽-1（GLP-1）受體激動劑治療伴心血管和腎臟風險的2型糖尿病患者的效果，研究組在Medline、Embase和Cochrane CENTRAL資料庫中檢索截至2020年8月11日的文獻，篩選出比較SGLT-2抑制劑或GLP-1受體激動劑與安慰劑、標準治療或其他降糖治療在2型糖尿病成人中的隨機對照試驗，隨訪時間為24周或更長時間。
將其匯總後進行隨機效應網絡薈萃分析，並使用GRADE評估證據的確定性。結果包括對極低風險（無心血管危險因素）、低風險（三個或以上心血管危險因素）、中等風險（心血管疾病）、高風險（慢性腎病）以及非常高的風險（心血管疾病和腎臟疾病）患者5年治療的每1000名患者的估計絕對療效。
研究組共納入764項試驗（包括421346名患者）。所有結果均涉及在現有糖尿病治療中添加SGLT-2抑制劑和GLP-1受體激動劑。這兩類藥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腎衰竭率（高確定性證據）。兩種藥物之間發現了顯著差異：SGLT-2抑制劑與比GLP-1受體激動劑相比，避免了更多患者死亡或因心力衰竭入院；而GLP-1受體激動劑與SGLT-2抑制劑相比，避免了更多患者發生非致命性中風。
SGLT-2抑制劑引發生殖器感染（高確定性），而GLP-1受體激動劑則可能引發嚴重的胃腸道事件（低確定性）。SGLT-2抑制劑和GLP-1受體激動劑可能會降低體重缺乏確定性的證據。幾乎沒有證明表明SGLT-2抑制劑或GLP-1受體激動劑對截肢、失明、眼病、神經性疼痛或健康相關生活質量有影響。這些藥物的絕對益處在不同的患者中有很大的差異，從心血管和腎臟結局的低風險到非常高的風險不等。
總之，對於2型糖尿病患者，SGLT-2抑制劑和GLP-1受體激動劑可降低心血管和腎臟病風險，其利弊也有顯著差異。
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