Metformin for Melanoma Holds Potential Benefits for Patients

A metformin (Glucophage) intervention showed promise for improving the overall survival (OS) rate of patients with melanoma, according to a recent study published in Frontiers Oncology. However, this result may be an indirect consequence of the drug as researchers were unable to conclude that metformin acted as a protective mechanism against melanoma.¹

Originally, metformin—an oral hypoglycemic—was indicated as a first-line treatment for patients with diabetes. Prior research eventually began recognizing the potential of metformin to protect against numerous cancers, including skin cancer. For example, in the last year a study conducted by Augustin et al found that patients with diabetes and melanoma saw significant 5-year improvements in disease recurrence (stage I/II: P = .012; stage III: P = .013) and reductions in brain metastases (P = .039) after exposure to metformin.²

Melanoma from sun exposure concept | image credit: bertys30 - stock.adobe.com

“Based on the progress of research on new targets and mechanisms of action of metformin, the target diseases of pharmacoepidemiological studies on this drug have gradually increased. The efficacy of metformin in various diseases has been confirmed by clinical studies, making metformin regarded as a ‘miracle drug’; its benefits include anti-aging, treatment of cognitive impairment, anti-cancer, and cardiovascular disease improvement,” the current authors wrote.¹

At present, the anti-cancer mechanism of metformin remains unclear. Additionally, analyses and studies conducted over recent years on metformin and skin cancer outcomes have been conflicting and overall inconclusive. Therefore, researchers conducted a meta-analysis to assess and update available evidence on the link between melanoma outcomes and metformin exposure.

Data were gathered from the Embase, Web of Science, PubMed and Cochrane Library systems through November 2023 using the keywords “metformin” and “melanoma.” A total of 12 studies were identified for the purpose of this analysis. Throughout these studies, 74,060/111,036 patients with melanoma across 9 countries received metformin.

Patients’ ages ranged from 57.6 to 73.4 years. There were 14,072 patients diagnosed with stage I melanoma, 7139 with stage II, 15 with stage III, and 253 with stage IV, respectively. Follow-ups were conducted for a range of 4.1 to 42.4 years and 3 (25%) of the included studies featured patients with type 2 diabetes.

Across 5 studies, data were available for the OS of 1521 patients. The administration of metformin was correlated with significant OS benefits in those treated (HR: 0.64; 95% CI, 0.42-1.00; P = .0004).

The 4 studies that included 933 patients with melanoma treated with metformin featured progressive-free survival (PFS) data. The HR of patients treated with metformin vs those who were not was not statistically significant (0.89; 95% CI 0.70-1.12). Recurrence-free survival, mortality rates, and objective response rates followed a similar trend.

In the realm of immune-related adverse events (irAEs), the authors noted that the differences between metformin groups and those without also was not statistically significant (OR: 1.01; 95% CI, 0.42-2.41). This trend continued as researchers analyzed melanoma incidence rates between groups treated and not treated with metformin (OR: 0.84; 95% CI, 0.40-1.78); however, a significant impact on HR was observed with incidence rates (0.94; 95% CI, 0.55-1.61; P = .005).

“These results also lead us to consider that metformin may indirectly affect disease survival through its protective effects on cell metabolism, anti-hyperglycemia, enhanced insulin sensitivity, reduced oxidative stress, and cardiovascular function,” the authors concluded.

References

1. Feng H, Shang S, Chen K, Sun X, Yue X. Impact of metformin on melanoma: a meta-analysis and systematic review. Front Oncol. 2024;14:1399693. doi:10.3389/fonc.2024.1399693

2. Augustin RC, Huang Z, Ding F, et al. Metformin is associated with improved clinical outcomes in patients with melanoma: a retrospective, multi-institutional study. Front Oncol. 2023;13:1075823. doi:10.3389/fonc.2023.1075823