Semaglutide use shows no significantly increased pancreatic cancer risk in meta-analysis of RCTs

GLP-1 receptor agonists like semaglutide are highly effective for type 2 diabetes and obesity, but concerns about potential links to pancreatic adverse events, including pancreatitis and pancreatic cancer, have persisted. Clarifying these risks is crucial for long-term patient safety and clinical decision-making, especially given the widespread and growing use of these medications. This meta-analysis aims to consolidate evidence from randomized trials to assess this specific risk.

Researchers conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the association between semaglutide use and the risk of pancreatic cancer. They systematically searched databases, identifying 1525 records and ultimately including 34 studies and reports. The primary endpoint was the incidence of pancreatic cancer, with secondary analysis on pancreatitis risk, assessing relative risks (RR) and 95% confidence intervals (CI).

The meta-analysis found no significantly increased risk of pancreatic cancer associated with GLP-1 RA use, including semaglutide. However, a statistically significant increased risk of pancreatitis was observed across all included trials, with a relative risk (RR) of 1.44 (95% CI 1.09-1.89, p = 0.009). This increased risk for pancreatitis did not remain significant when studies were stratified by background medications (RR: 1.28, 95% CI 0.87-1.87) or when considering only studies without background medications (RR: 1.37, 95% CI 0.91-2.05). This suggests the initial pancreatitis signal might be influenced by confounding factors or heterogeneity among studies.