Tang Huilin, Zhang Bingyu, Lu Yiwen, Donahoo William T, Singh Ospina Naykky, Kotecha Pareeta, Lu Ying, Tong Jiayi, Smith Steven M, Rosenberg Eric I, Kimmel Stephen E, Bian Jiang, Guo Jingchuan, Chen Yong
Department of Pharmaceutical Outcomes and Policy, University of Florida College of Pharmacy, Gainesville, Florida, USA.
The Center for Health AI and Synthesis of Evidence (CHASE), University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Diabetes Obes Metab. 2025 Mar;27(3):1444-1455. doi: 10.1111/dom.16147. Epub 2024 Dec 26.
To comprehensively evaluate the benefits and risks of glucagon-like peptide-1 receptor agonists (GLP-1RA), dipeptidyl peptidase 4 inhibitors (DPP4i), and sodium-glucose cotransporter 2 inhibitors (SGLT2i).
A systematic search of PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to November 2023 to identify randomized cardiovascular and kidney outcome trials that enrolled adults with type 2 diabetes, heart failure, or chronic kidney disease and compared DPP4i, GLP-1RAs, or SGLT2i to placebo. Twenty-one outcomes (e.g., major adverse cardiovascular events [MACE], stroke, and hospitalization for heart failure [HHF]) were assessed. Data were pooled using population-averaged odds ratios (ORs) with 95% CIs.
Twenty-six trials enrolling 198 177 participants were included. GLP-1RAs were most effective in lowering the risks of MACE (OR, 0.85, [95% CI, 0.79 to 0.92]) and stroke (0.84 [0.77, 0.91]), but increased the risk of thyroid cancer (1.58 [1.36, 2.50]). SGLT2i showed the greatest benefits in reducing the risk of HHF (0.68 [0.64, 0.73]) and improving composite renal outcomes (0.67 [0.58, 0.77]), but increased the risk of genital infections (3.11 [2.15, 4.50]). DPP4i were associated with a lower risk of certain psychiatric disorders, Parkinson's disease (0.54 [0.32, 0.92]), and amputation (0.70 [0.86, 0.93]), but an increased risk of neuropathy (1.10 [1.02, 1.18]) and pancreatitis (1.63 [1.40, 1.91]). The weighted origami plot suggested that GLP-1RAs were more suitable for reducing macrovascular and microvascular outcomes, while DPP4i might be better for neurodegenerative diseases and cancer concerns.
Given the distinct benefit-risk profiles, the selection of glucose-lowering drugs should be individualized based on patient characteristics and risk factors.
全面评估胰高血糖素样肽-1受体激动剂（GLP-1RA）、二肽基肽酶4抑制剂（DPP4i）和钠-葡萄糖协同转运蛋白2抑制剂（SGLT2i）的获益与风险。
对PubMed、EMBASE和Cochrane对照试验中心注册库（CENTRAL）进行系统检索，检索时间从建库至2023年11月，以确定纳入2型糖尿病、心力衰竭或慢性肾脏病成年患者并比较DPP4i、GLP-1RA或SGLT2i与安慰剂的随机心血管和肾脏结局试验。评估了21项结局（如主要不良心血管事件[MACE]、中风和心力衰竭住院[HHF]）。使用人群平均比值比（OR）及95%置信区间（CI）对数据进行汇总。
纳入了26项试验，共198177名参与者。GLP-1RA在降低MACE风险（OR，0.85，[95%CI，0.79至0.92]）和中风风险（0.84[0.77，0.91]）方面最有效，但增加了甲状腺癌风险（1.58[1.36，2.50]）。SGLT2i在降低HHF风险（0.68[0.64，0.73]）和改善复合肾脏结局（0.67[0.58，0.77]）方面显示出最大获益，但增加了生殖器感染风险（3.11[2.15，4.50]）。DPP4i与某些精神障碍、帕金森病（0.54[0.32，0.92]）和截肢（0.70[0.86，0.93]）风险较低相关，但增加了神经病变（1.10[1.02，1.
