The first study was an international, multicentre cohort study comparing incretin therapies (DPP-4 inhibitors or glucagon-like peptide-1 receptor agonists) with sulfonylureas in terms of pancreatic cancer risk in 972 384 people with diabetes. Over a median follow-up ranging from 1.3 to 2.8 years in the different centres (maximum follow-up, 8 years), 1221 participants were diagnosed with pancreatic cancer (incidence rate 0.60 per 1000 person-years). Compared with sulfonylurea users, the pooled adjusted hazard ratio was 1.02 (95% confidence interval [CI], 0.84–1.23). Risk did not vary by class of drug and there was no evidence of a duration–response relationship.
The second study was a meta-analysis of 43 randomised controlled trials (n=68 775) and 12 observational studies (n=1 777 358) comparing DPP-4 inhibitors against placebo, lifestyle modification or other antidiabetes drugs in terms of HF risk. Moderate-quality evidence from five randomised controlled trials showed that, compared with controls, DPP-4 inhibitors increased the risk of hospital admission for HF among people with known cardiovascular disease (odds ratio [OR], 1.13; 95% CI, 1.00–1.26). Low-quality evidence from the 38 randomised controlled trials evaluating risk of HF not limited to hospital admissions demonstrated no significant risk (OR, 0.97; 95% CI, 0.61–1.56), and the evidence from observational studies was of very low quality.
While these findings are reassuring about pancreatic cancer risk, clinicians may want to exercise caution when offering DPP-4 inhibitors to people who are at high risk of heart failure.
