BACKGROUND Considering the global burden of diabetes and associated cardiovascular disease, an urgent need exists for the best treatment, which should be based on the best available evidence. We examined the association between glucose-lowering medications and a broad range of cardiovascular outcomes, and assessed the strength of evidence for these associations. METHODS For this umbrella review we searched PubMed, Embase, and the Cochrane Library to identify systematic reviews and meta-analyses of randomised controlled trials examining the cardiovascular safety of glucose-lowering medications. Cardiovascular outcomes examined included major adverse cardiovascular events, cardiovascular death, myocardial infarction, stroke, heart failure, unstable angina, and atrial fibrillation. For each meta-analysis, we estimated the relative risk (RR) and 95% CI. We also created an evidence map showing the plausible benefits or harms of each intervention and the certainty of the evidence. FINDINGS We examined 232 meta-analyses evaluating ten classes of diabetes drugs. We identified six risk and 38 protective associations showing a high strength of evidence. Six associations increased the risk of cardiovascular disease, including glimepiride (stroke [RR 2·01; 95% CI 1·02-3·98]), rosiglitazone (myocardial infarction [1·28; 1·02-1·62] and heart failure [1·72, 1·31-2·27]), and pioglitazone (heart failure [1·40; 1·16-1·69]). 38 associations decreased the risk of cardiovascular disease, including glucagon-like peptide-1 receptor agonists as a class (major adverse cardiovascular events [RR 0·88; 95% CI 0·84-0·92], death from cardiovascular disease [0·87; 0·81-0·94], myocardial infarction [0·92; 0·86-0·99], stroke [0·84; 0·77-0·93], and heart failure [0·90; 0·83-0·99]), albiglutide (major adverse cardiovascular events [0·81; 0·68-0·96], myocardial infarction [0·77; 0·64-0·92], and heart failure [0·71; 0·55-0·93]), dulaglutide (stroke [0·78; 0·64-0·96]), exenatide (major adverse cardiovascular events [0·91; 0·83-1·00]), liraglutide (major adverse cardiovascular events [0·86; 0·77-0·96]), semaglutide (major adverse cardiovascular events [0·76; 0·62-0·92] and stroke [0·67; 0·45-1·00]), sodium-glucose co-transporter-2 inhibitors as a class (major adverse cardiovascular events [0·87; 0·82-0·93], death from cardiovascular disease [0·82; 0·75-0·90], myocardial infarction [0·86; 0·78-0·94], and heart failure [0·68; 0·63-0·73]), canagliflozin (major adverse cardiovascular events [0·84; 0·75-0·93], death from cardiovascular disease [0·82; 0·71-0·96], and heart failure [0·65; 0·54-0·78]), dapagliflozin (heart failure [0·70; 0·60-0·82]), empagliflozin (major adverse cardiovascular events [0·85; 0·77-0·94], death from cardiovascular disease [0·62; 0·50-0·78], and heart failure [0·64; 0·53-0·77]), and pioglitazone (major adverse cardiovascular events [0·84; 0·74-0·96], myocardial infarction [0·80; 0·67-0·95], and stroke [0·79; 0·65-0·95]). INTERPRETATION We found varied levels of evidence for the associations between diabetes drugs and cardiovascular outcomes; some drugs raised the risk of cardiovascular disease, whereas others showed benefit. FUNDING None.

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降糖药物与心血管预后的关联：综述和证据图。

背景技术考虑到糖尿病和相关心血管疾病的全球负担，迫切需要最好的治疗方法，该方法应基于最佳的现有证据。我们研究了降糖药物与广泛的心血管结局之间的关联，并评估了这些关联的证据强度。方法对于这项总括性综述，我们搜索了PubMed，Embase和Cochrane库，以鉴定检查降糖药物心血管安全性的随机对照试验的系统评价和荟萃分析。检查的心血管结局包括主要的不良心血管事件，心血管死亡，心肌梗塞，中风，心力衰竭，不稳定型心绞痛和心房颤动。对于每个荟萃分析，我们估算了相对风险（RR）和95％CI。我们还创建了一个证据图，显示了每种干预措施的合理利益或危害以及证据的确定性。结果我们检查了232项荟萃分析，评估了十类糖尿病药物。我们确定了六种风险关联和38种保护关联，它们具有很高的证据强度。有六个协会增加了心血管疾病的风险，包括格列美脲（中风[RR 2·01； 95％CI 1·02-3·98]），罗格列酮（心肌梗塞[1·28； 1·02-1·62]和心力衰竭[1·72、1·31-2·27]和吡格列酮（心力衰竭[1·40； 1·16-1·69]）。38个协会降低了心血管疾病的风险，包括胰高血糖素样肽1受体激动剂一类（严重的不良心血管事件[RR 0·88； 95％CI 0·84-0·92]，心血管疾病的死亡[0 ·87; 0·81-0·94]，心肌梗塞[0·92；0·86-0·99]，笔画[0·84; 0·77-0·93]和心力衰竭[0·90; 0 0·83-0·99]，阿比鲁肽（主要不良心血管事件[0·81； 0·68-0·96]，心肌梗塞[0·77； 0·64-0·92]和心力衰竭[ 0·71； 0·55-0·93]），杜拉鲁肽（中风[0·78； 0·64-0·96]），艾塞那肽（主要不良心血管事件[0·91； 0·83-1·00] ]），利拉鲁肽（主要不良心血管事件[0·86; 0·77-0·96]），司马鲁肽（主要不良心血管事件[0·76; 0·62-0·92]和中风[0·67; [0·45-1·00]），钠-葡萄糖共转运蛋白2抑制剂作为一类（重大不良心血管事件[0·87; 0·82-0·93]，心血管疾病死亡[0·82; 0]; 0·75-0·90]，心肌梗死[0·86; 0·78-0·94]和心力衰竭[0·68; 0·63-0·73]），canagliflozin（主要的不良心血管事件[ 0·84; 0·75-0·93]，死于心血管疾病[0·82; 0·71-0·96]和心力衰竭[0·65; 0·54-0·78]），达格列净（心力衰竭[0·70; 0·60-0·82]），依帕格列净（主要不良心血管事件[0·85; 0·77-0·94]，死亡源自心血管疾病[0·62; 0·50-0·78]和心力衰竭[0·64; 0·53-0·77]）和吡格列酮（主要不良心血管事件[0·84; 0·74] -0·96]，心肌梗死[0·80; 0·67-0·95]和中风[0·79; 0·65-0·95]）。解释我们发现糖尿病药物与心血管预后之间相关性的证据水平各不相同。一些药物增加了患心血管疾病的风险，而另一些药物则显示了获益。资金无。0·77-0·94]，死于心血管疾病[0·62; 0·50-0·78]和心力衰竭[0·64; 0·53-0·77]）和吡格列酮（主要不良心血管事件[0·84； 0·74-0·96]，心肌梗塞[0·80； 0·67-0·95]和中风[ 0·79； 0·65-0·95]）。解释我们发现糖尿病药物与心血管预后之间相关性的证据水平各不相同。一些药物增加了患心血管疾病的风险，而另一些药物则显示了获益。资金无。0·77-0·94]，死于心血管疾病[0·62; 0·50-0·78]和心力衰竭[0·64; 0·53-0·77]）和吡格列酮（主要不良心血管事件[0·84； 0·74-0·96]，心肌梗塞[0·80； 0·67-0·95]和中风[ 0·79； 0·65-0·95]）。解释我们发现糖尿病药物与心血管预后之间相关性的证据水平各不相同。一些药物增加了患心血管疾病的风险，而另一些药物则显示了获益。资金无。一些药物增加了患心血管疾病的风险，而另一些药物则显示了获益。资金无。一些药物增加了患心血管疾病的风险，而另一些药物则显示了获益。资金无。