Back to 2025 Abstracts
METFORMIN USE WAS CORRELATED WITH A LOWER LONGITUDINAL RISK OF A DIAGNOSIS OF MALIGNANT NEUROENDOCRINE TUMOR (NET) IN PATIENTS WITH A PREVIOUSLY BENIGN NET
Luis F. Lara
*, Milton Smith, Moamen Gabr, Muhammad H. Dawwas, Andrew Ofosu, Rosanne Danielson, Wei-Wen Hsu, Inuk Zandvakili, Mubarak Sayyar, Davendra Sohal, Jordan Kharofa, Sameer Patel, Gregory C. Wilson, Syed Ahmad
University of Cincinnati, Cincinnati, OH
Introduction
Neuroendocrine tumors (NET) are uncommon, but their incidence is increasing. They are mostly indolent and there is no strategy to prevent malignant transformation. Metformin is used to treat diabetes mellitus type 2 and regulates important cellular regulatory pathways such as AMPK and the mTOR complex which when dysregulated contributes to the progression of NET. We evaluated if metformin use affected the diagnosis of malignant NET in subjects with an initially benign NET diagnosis.
Methods
The international electronic medical database TriNetX (Cambridge, MA) was used to find patients > 18 y/o with a diagnosis of benign NET from 2014 to 2024. This is an international de-identified electronic database comprising over 315 million subjects, and mostly from the United States. Data from 66 health care organizations were included. Co-variates included age, sex, race, body weight, smoking status, alcohol related disorders and proton pump inhibitor (PPI) use, and comparison outcomes included 19 exclusion criteria (including previous pancreas surgeries and malignant neoplasm of the pancreas), 15 ICD-10 codes for malignant NET, and 16 CPT codes. Subjects in the study group had to be on metformin for at least one year, and the diagnosis of malignant NET was at least 3 years after the initial diagnosis of benign NET in both groups, on and off metformin. Subjects were followed longitudinally and were 1:1 propensity score matched. P <0.001 was significant.
Results
There were 1,478 patients with benign NET on metformin and 34,909 patients with benign NET not taking metformin. After propensity score matching there were 1,460 patients in each group. The average age was 63.4 ±13 in the NET and metformin group, and 67.3 ±13.2 in the group not taking metformin. There were 878 were females, 16.5% were African American and 7.5% were Hispanic. The risk of being diagnosed subsequently with a malignant NET while on metformin was significantly lower at 5.3% (78 patients) and it was 9.7% in patients not taking metformin (142 patients), RR 1.8 (95% CI 1.3,2.3), P<0.001.
Discussion
In this large database of subjects with an initial benign NET who were followed longitudinally the risk of subsequent diagnosis of malignant NET was significantly lower in the group taking metformin. Indication and lead-time biases were decreased be being on metformin for at least one year and the diagnosis of malignant NET was at least 3 years after the initial diagnosis of benign NET. Metformin concentrates much higher in the cytosol compared to serum. It inhibits the mTOR complex directly or indirectly via AMPK activation. There is a plausible biological explanation why metformin may play a role in NET growth, including malignant transformation. The effects of other confounders need to be considered, but metformin as a NET disease modifier merits further study.
Back to 2025 Abstracts
