Melanie J. Davies

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.

Inequalities in cancer mortality trends in people with type 2 diabetes: 20 year population-based study in England

Abstract Aims/hypothesis The aim of this study was to describe the long-term trends in cancer mortality rates in people with type 2 diabetes based on subgroups defined by sociodemographic characteristics and risk factors. Methods We defined a cohort of individuals aged ≥35 years who had newly diagnosed type 2 diabetes in the Clinical Practice Research Datalink between 1 January 1998 and 30 November 2018. We assessed trends in all-cause, all-cancer and cancer-specific mortality rates by age, gender, ethnicity, socioeconomic status, obesity and smoking status. We used Poisson regression to calculate age- and calendar year-specific mortality rates and Joinpoint regression to assess trends for each outcome. We estimated standardised mortality ratios comparing mortality rates in people with type 2 diabetes with those in the general population. Results Among 137,804 individuals, during a median follow-up of 8.4 years, all-cause mortality rates decreased at all ages between 1998 and 2018; cancer mortality rates also decreased for 55- and 65-year-olds but increased for 75- and 85-year-olds, with average annual percentage changes (AAPCs) of –1.4% (95% CI –1.5, –1.3), –0.2% (–0.3, –0.1), 1.2% (0.8, 1.6) and 1.6% (1.5, 1.7), respectively. Higher AAPCs were observed in women than men (1.5% vs 0.5%), in the least deprived than the most deprived (1.5% vs 1.0%) and in people with morbid obesity than those with normal body weight (5.8% vs 0.7%), although all these stratified subgroups showed upward trends in cancer mortality rates. Increasing cancer mortality rates were also observed in people of White ethnicity and former/current smokers, but downward trends were observed in other ethnic groups and non-smokers. These results have led to persistent inequalities by gender and deprivation but widening disparities by smoking status. Constant upward trends in mortality rates were also observed for pancreatic, liver and lung cancer at all ages, colorectal cancer at most ages, breast cancer at younger ages, and prostate and endometrial cancer at older ages. Compared with the general population, people with type 2 diabetes had a more than 1.5-fold increased risk of colorectal, pancreatic, liver and endometrial cancer mortality during the whole study period. Conclusions/interpretation In contrast to the declines in all-cause mortality rates at all ages, the cancer burden has increased in older people with type 2 diabetes, especially for colorectal, pancreatic, liver and endometrial cancer. Tailored cancer prevention and early detection strategies are needed to address persistent inequalities in the older population, the most deprived and smokers. Graphical abstract