Diabetology, Careggi Hospital and University of Florence, Firenze, Italy.
Endocrinology and Metabolic Diseases Unit, AO SS. Antonio e Biagio e Cesare Arrigo, Alessandria, Italy.
Diabetes Obes Metab. 2023 Feb;25(2):444-453. doi: 10.1111/dom.14888. Epub 2022 Oct 24.
To investigate the effects of glucose-lowering agents on all-cause mortality, and cardiovascular and renal outcomes in adults with type 2 diabetes.
A MEDLINE and EMBASE search was performed to identify randomized controlled trials, published up to 28 February 2022, with a follow-up ≥52 weeks, in which glucose-lowering drugs were compared with either placebo or active comparators. We included only trials reporting formal external adjudication of events. All-cause mortality, 3-point MACE (major cardiovascular events), and hospitalization for heart failure (HHF) were considered as principal outcomes. Doubling of serum creatinine, worsening albuminuria, and renal death were considered as secondary endpoints.
We included randomized controlled trials performed on metformin (n = 17), pioglitazone (n = 20), alpha-glucosidase inhibitors (n = 9), insulin secretagogues (n = 42), dipeptidyl-peptidase-4 inhibitors (n = 67), glucagon-like peptide-1 receptor agonists (n = 45) or sodium-glucose co-transporter-2 inhibitors (SGLT-2i; n = 42) and insulin (n = 18). Glucagon-like peptide-1 receptor agonist and SGLT-2i were associated with a significant reduction in all-cause mortality [Mantel-Haenszel odds ratio (MH-OR), 95% confidence interval: 0.88 (0.83; 0.95) and 0.85 (0.79; 0.91), respectively] and MACE [MH-OR, 95% confidence interval: 0.89 (0.84; 0.94) and 0.90 (0.84; 0.96), respectively]. SGLT-2i was associated with a reduced risk of HHF [MH-OR 0.68 (0.62; 0.75)], worsening albuminuria [MH-OR 0.67 (0.55; 0.80)] and doubling of serum creatinine [MH-OR 0.58 (0.44; 0.79)]. Metformin and pioglitazone were associated with a significantly lower risk of MACE [MH-OR 0.60 (0.47; 0.80) and 0.85 (0.74; 0.97), respectively] and pioglitazone with a higher risk of HHF [MH-OR 1.30 (1.04; 1.62)]. Insulin secretagogues were associated with increased risk of all-cause mortality [MH-OR 1.12 (1.01; 1.24)] and MACE [MH-OR 1.19 (1.02; 1.39)].
The results of this updated meta-analysis need to be considered in the choice of drug treatment for type 2 diabetes mellitus, which cannot be merely based on the effect of glucose-lowering drugs on long-term glycaemic control.
探讨降糖药物对 2 型糖尿病患者全因死亡率以及心血管和肾脏结局的影响。
对 MEDLINE 和 EMBASE 进行了检索，以确定截至 2022 年 2 月 28 日、随访时间≥52 周、比较降糖药物与安慰剂或阳性对照的随机对照试验。我们仅纳入了报告正式外部事件裁决的试验。全因死亡率、3 点主要心血管事件（MACE）和心力衰竭住院（HHF）被视为主要结局。血清肌酐加倍、白蛋白尿恶化和肾脏死亡被视为次要终点。
我们纳入了在二甲双胍（n=17）、吡格列酮（n=20）、α-葡萄糖苷酶抑制剂（n=9）、胰岛素促分泌剂（n=42）、二肽基肽酶-4 抑制剂（n=67）、胰高血糖素样肽-1 受体激动剂（n=45）或钠-葡萄糖共转运蛋白-2 抑制剂（SGLT-2i；n=42）和胰岛素（n=18）上进行的随机对照试验。胰高血糖素样肽-1 受体激动剂和 SGLT-2i 与全因死亡率显著降低相关[Mantel-Haenszel 优势比（MH-OR），95%置信区间：0.88（0.83；0.95）和 0.85（0.79；0.91）]和 MACE[MH-OR，95%置信区间：0.89（0.84；0.94）和 0.90（0.84；0.96）]。SGLT-2i 与 HHF 风险降低相关[MH-OR 0.68（0.62；0.75）]、白蛋白尿恶化[MH-OR 0.67（0.55；0.80）]和血清肌酐加倍[MH-OR 0.58（0.44；0.79）]。二甲双胍和吡格列酮与 MACE 风险显著降低相关[MH-OR 0.60（0.47；0.80）和 0.85（0.74；0.97）]，吡格列酮与 HHF 风险增加相关[MH-OR 1.30（1.04；1.62）]。胰岛素促分泌剂与全因死亡率增加相关[MH-OR 1.12（1.01；1.24）]和 MACE[MH-OR 1.19（1.02；1.39）]。
本更新的荟萃分析结果需要在选择 2 型糖尿病药物治疗时加以考虑，而不能仅仅基于降糖药物对长期血糖控制的影响。
