Ko Hwa Yeon, Bea Sungho, Yoon Dongwon, Hong Bin, Bae Jae Hyun, Cho Young Min, Shin Ju-Young
School of Pharmacy, Sungkyunkwan University, Suwon-si, South Korea.
Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Lancet Reg Health West Pac. 2025 Mar 10;56:101242. doi: 10.1016/j.lanwpc.2024.101242. eCollection 2025 Mar.
Despite emerging evidence of gallbladder or biliary tract diseases (GBD) risk regarding incretin-based drugs, population-specific safety profile considering obesity is lacking. We aimed to assess whether stratification by body mass index (BMI) modifies the measures of association between incretin-based drugs and the risk of GBD.
We conducted an active-comparator, new-user cohort study using a nationwide claims data (2013-2022) of Korea. We included type 2 diabetes (T2D) patients stratified by Asian BMI categories: Normal, 18.5 to <23 kg/m; Overweight, 23 to <25 kg/m; Obese, ≥25 kg/m. The primary outcome was a composite of GBD, including cholelithiasis, cholecystitis, obstruction of the gallbladder or bile duct, cholangitis, and cholecystectomy. We used 1:1 propensity score (PS) matching and estimated hazard ratios (HR) with 95% confidence intervals (CI) using Cox models.
New users of DPP4i and SGLT2i were 1:1 PS matched (n = 251,420 pairs; 186,697 obese, 39,974 overweight, and 24,749 normal weight pairs). The overall HR for the risk of GBD with DPP4i vs. SGLT2i was 1.21 (95% CI 1.14-1.28), with no effect modification by BMI (p-value: 0.83). For the second cohort, new users of GLP1RA and SGLT2i were 1:1 PS matched (n = 45,443 pairs; 28,011 obese, 8948 overweight, and 8484 normal weight pairs). The overall HR for the risk of GBD with GLP1RA vs. SGLT2i was 1.27 (1.07-1.50), with no effect modification by BMI (p-value: 0.73).
The increased risks of GBD were presented in both cohorts with no evidence of effect heterogeneity by BMI.
Ministry of Food and Drug Safety, Health Fellowship Foundation.
尽管有新证据表明基于肠促胰岛素的药物存在胆囊或胆道疾病（GBD）风险，但缺乏考虑肥胖因素的特定人群安全性概况。我们旨在评估按体重指数（BMI）分层是否会改变基于肠促胰岛素的药物与GBD风险之间的关联度量。
我们使用韩国全国范围的索赔数据（2013 - 2022年）进行了一项活性对照、新使用者队列研究。我们纳入了按亚洲BMI类别分层的2型糖尿病（T2D）患者：正常，18.5至<23kg/m²；超重，23至<25kg/m²；肥胖，≥25kg/m²。主要结局是GBD的复合结局，包括胆结石、胆囊炎、胆囊或胆管梗阻、胆管炎和胆囊切除术。我们使用1:1倾向评分（PS）匹配，并使用Cox模型估计风险比（HR）及95%置信区间（CI）。
DPP4i和SGLT2i的新使用者进行了1:1 PS匹配（n = 251,420对；186,697对肥胖、39,974对超重和24,749对正常体重）。DPP4i与SGLT2i相比，GBD风险的总体HR为1.21（95% CI 1.14 - 1.28），BMI无效应修饰（p值：0.83）。对于第二个队列，GLP1RA和SGLT2i的新使用者进行了1:1 PS匹配（n = 45,443对；28,011对肥胖、8,948对超重和8,484对正常体重）。GLP1RA与SGLT2i相比，GBD风险的总体HR为1.27（1.07 - 1.50），BMI无效应修饰（p值：0.73）。
两个队列均显示GBD风险增加，且无BMI效应异质性的证据。
食品药品安全部、健康奖学金基金会。
