Weight loss interventions and obesity‐associated cancers in people with type 2 diabetes and overweight/obesity: A real‐world observational study
Abstract
Aims
To evaluate whether weight‐loss interventions are associated with obesity‐associated cancers (OAC) in individuals with overweight/obesity and type 2 diabetes (T2D).
Materials and Methods
This retrospective cohort study utilised the TriNetX federated research network. Three cohorts of adults with overweight/obesity and T2D, treated with either semaglutide, tirzepatide or bariatric surgery (BS) between June 2005 and June 2025, were propensity score matched (1:1) to cohorts treated with dipeptidyl peptidase‐4 inhibitors (DPP‐4i) using potential confounding factors. Using Cox regression analysis, we estimated hazard ratios (HRs) of composite and individual OAC: breast, colorectal, gallbladder, liver, multiple myeloma, oesophageal, ovarian, pancreatic, renal, gastric cardia, thyroid and uterine cancers.
Results
In 64,178 matched pairs (mean follow‐up 911 days), semaglutide (vs. DPP‐4i) was associated with lower rates of composite OAC (HR: 0.88; 95% CI: 0.82–0.95), colorectal (0.80; 0.67–0.97), liver (0.75; 0.60–0.95) and pancreatic (0.76; 0.60–0.96) cancers. In 19,682 matched pairs (mean follow‐up 435 days), tirzepatide (vs. DPP‐4i) was associated with a non‐significant lower rate of composite OAC (0.84; 0.69–1.01) but a significant lower rate of ovarian cancer (0.31; 0.10–0.95). In 9642 matched pairs (mean follow‐up 1746 days), BS (vs. DPP‐4i) was associated with lower rates of composite OAC (0.85; 0.74–0.98), liver (0.56; 0.32–0.97) and uterine cancers (0.59; 0.38–0.90), and higher rates of gastric cardia cancer (10.54; 1.35–82.38) and oesophageal cancer (4.78; 1.04–21.87).
Conclusions
Semaglutide and BS were associated with lower cancer rates in individuals with overweight/obesity and T2D, with non‐significant lower rates also observed with tirzepatide. These findings suggest weight‐loss interventions may contribute to cancer prevention in this population.