Ayoub Mark, Aibani Rafi, Dodd Tiana, Ceesay Muhammed, Bhinder Muhammad, Faris Carol, Amin Nisar, Daglilar Ebubekir
Department of Internal Medicine, Charleston Area Medical Center, West Virginia University, Charleston, WV 25304, USA.
Department of Internal Medicine, Bayonne Medical Center, Bayonne, NJ 07002, USA.
Cancers (Basel). 2024 Sep 22;16(18):3224. doi: 10.3390/cancers16183224.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are becoming more popular in managing type 2 diabetes mellitus (T2DM). Concerns linger over potential links to malignancies like pancreatic and thyroid cancers, requiring more research to clarify their safety profiles. Additionally, evidence suggests GLP-1 RAs may lower colorectal and pancreatic cancer risk, especially in obese and overweight individuals, indicating a protective effect beyond weight loss. Current studies leave a gap in comprehensively understanding cancer risks associated with GLP-1 RAs, which prompts further research to enhance our understanding of their overall safety.
We queried the US Collaborative Network (63 health care organizations) of the TriNetX research database. Patients with T2DM were identified and divided into two cohorts: patients on GLP-1 RAs and patients not on GLP-1 RAs. We excluded tobacco use and alcohol use disorders, obese patients with a body mass index (BMI) of >25 kg/m, and those with a family history of gastrointestinal malignancy, infectious mononucleosis, chronic gastritis, pernicious anemia, helicobacter pylori infection, or gastroesophageal reflux disease (GERD). We used a 1:1 propensity score matching (PSM) model using patients' baseline characteristics, medications, labs, and genetics. We compared the rate of gastric cancer and esophageal cancer at the seven-year mark.
A total of 2,748,431 patients with T2DM were identified. Of those, 6% ( = 167,077) were on a GLP-1 RA and 94% ( = 2,581,354) were not on a GLP-1 RA. After PSM, both cohorts included 146,277 patients. Patients with T2DM who were on a GLP-1 RA, compared to those who were not, had a statistically significant lower risk of both gastric cancer (0.05% vs. 0.13%, < 0.0001) and esophageal cancer (0.04% vs. 0.13%, < 0.0001) at the seven-year mark.
The use of GLP-1 RAs in patients with T2DM does not significantly increase the risk of gastric or esophageal cancer. This finding supports the continued use of GLP-1 analogues as a therapeutic option in managing T2DM, considering their well-established benefits and low risk of complications. Based on the study results, these medications may even have a protective effect against these malignancies.
胰高血糖素样肽-1受体激动剂（GLP-1 RAs）在2型糖尿病（T2DM）管理中越来越受欢迎。人们对其与胰腺癌和甲状腺癌等恶性肿瘤的潜在联系仍存担忧，需要更多研究来阐明其安全性。此外，有证据表明GLP-1 RAs可能降低结直肠癌和胰腺癌风险，尤其是在肥胖和超重个体中，这表明其保护作用不仅仅是体重减轻。目前的研究在全面了解与GLP-1 RAs相关的癌症风险方面存在差距，这促使进一步研究以增进我们对其整体安全性的理解。
我们查询了TriNetX研究数据库的美国协作网络（63个医疗保健组织）。识别出T2DM患者并将其分为两个队列：使用GLP-1 RAs的患者和未使用GLP-1 RAs的患者。我们排除了吸烟和酒精使用障碍、体重指数（BMI）>25 kg/m²的肥胖患者以及有胃肠道恶性肿瘤、传染性单核细胞增多症、慢性胃炎、恶性贫血、幽门螺杆菌感染或胃食管反流病（GERD）家族史的患者。我们使用1:1倾向评分匹配（PSM）模型，依据患者的基线特征、药物、实验室检查和基因情况进行匹配。我们比较了七年时胃癌和食管癌的发生率。
共识别出2,748,431例T2DM患者。其中，6%（n = 167,077）使用GLP-1 RA，94%（n = 2,581,354）未使用GLP-1 RA。经过PSM后，两个队列各有146,277例患者。与未使用GLP-1 RA的T2DM患者相比，使用GLP-1 RA的患者在七年时患胃癌（0.05%对0.13%，P < 0.0001）和食管癌（0.04%对0.13%，P < 0.0001）的风险在统计学上显著更低。
在T2DM患者中使用GLP-1 RAs不会显著增加胃癌或食管癌风险。考虑到GLP-1类似物已确立的益处和较低的并发症风险，这一发现支持继续将其作为治疗T2DM的一种选择。基于研究结果，这些药物甚至可能对这些恶性肿瘤有保护作用。
