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Anti-Diabetic Pharmacotherapy and Cancer-Related Lymphedema: Mechanistic Rationale and Clinical Evidence
Stav Brown, MD, Sarah Fargey, BS, Geronimo Salcedo, BS, Rohan Kumaran, BS, Mehra Golshan, MD MBA, Siba Haykal MD PhD
1. Yale School of Medicineool, New Haven, CT, United States.
Background:Cancer-related lymphedema remains a chronic and largely incurable condition treated primarily with supportive therapies. Metabolic dysfunction"”including diabetes, obesity, and chronic inflammation"”has been implicated in lymphatic injury and impaired lymphatic repair. We synthesized the available evidence evaluating anti-diabetic pharmacotherapy in the context of cancer-related lymphedema.
Methods:A structured review of clinical studies evaluating anti-diabetic medications and lymphedema outcomes was performed. Quantitative pooling was conducted for cohort studies evaluating glucagon-like peptide-1 receptor agonists (GLP-1RAs) and lymphedema incidence.
Results:Seven studies met inclusion criteria representing
over 500,000 patients. Three anti-diabetic drug classes were evaluated.
Metformin was examined in
one retrospective cohort study involving
4,882 patients undergoing axillary lymph node dissection and was associated with a
38 percent reduction in BCRL risk (hazard ratio 0.62).
GLP-1 receptor agonists were evaluated in
4 clinical studies involving
over 495,000 patients. Exploratory quantitative synthesis of GLP-1RA cohort data (
n = 5,168 patients) demonstrated a pooled
risk ratio of 0.41 (95 percent CI, 0.26-0.65), corresponding to an approximate
59 percent relative reduction in lymphedema risk.
SGLT-2 inhibitors were evaluated in
1 clinical case report demonstrating improvement in systemic lymphedema in the setting of severe metabolic disease.
Conclusions:This is the first and largest study to summarize the evidence regarding the effect of anti-diabetic drugs on cancer related lymphedema. Across 7 studies including more than half a million patients, anti-diabetic pharmacotherapy"”particularly metformin and GLP-1 receptor agonists"”demonstrates consistent signals suggesting potential risk reduction and disease modification in cancer-related lymphedema. These findings support further prospective investigation of metabolic therapies for lymphedema prevention and management.
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