Metformin: An Effective Treatment of Lung Cancer Among Patients With Obesity?

By: Chris Schimpf, MSW
Posted: Thursday, December 12, 2024

New research published in the Journal of the National Cancer Institute suggests that the diabetes drug metformin may yield an anticancer effect in patients with lung cancer who have obesity, improving lung cancer–specific clinical outcomes within this population. Sai Yendamuri, MD, MBA, FACS, of Roswell Park Comprehensive Cancer Center, Buffalo, New York, and colleagues identified obesity as a potential predictive biomarker of metformin’s anticancer and immunotherapy-enhancing properties among patients with lung cancer and reported on some of the underlying immunologic phenomena. A phase II clinical trial is under way.

“Metformin has been used for 30 years and has a long record of safety—and it’s one of the most widely accessible and affordable drugs of any kind. If we can repurpose it to fight cancer, that’s very exciting,” said Dr. Yendamuri in an institutional press release.

The study combined retrospective analyses of data from two clinical cohorts with complementary preclinical mouse models conducted by the investigators. One cohort included patients with non–small cell lung cancer (NSCLC) who underwent lobectomy, divided into those with an “overweight” body mass index (BMI) defined as 25 kg/m² or greater (n = 511) and a “nonoverweight” BMI defined as lower than 25 kg/m² (n = 232). The other cohort included patients with NSCLC who underwent treatment with immune checkpoint inhibitors, divided into the same overweight (n = 284) and nonoverweight (n = 184) categories.

The investigators reported that metformin was associated with increased recurrence-free survival in overweight patients after lobectomy (hazard ratio [HR] = 0.47; 95% confidence interval [CI] = 0.24–0.94]; P = .035). In diet-induced obese mouse models, they observed it corrected accelerated tumor growth in a lymphocyte-specific manner while reversing several mechanisms of immune suppression potentiated by obesity. In addition, PD-1 blockade coupled with metformin was more effective at limiting tumor burden in obese mice and correlated with progression-free survival only in patients with overweight given immunotherapy (HR = 0.60; 95% CI = 0.39-0.93]; P = .024).

Disclosure: The study authors reported no conflicts of interest.

Journal of the National Cancer Institute