Glucagon-like peptide 1 receptor agonists (GLP-1RAs) demonstrate glucose-lowering, weight-reducing, and favourable anti-inflammatory and metabolic effects.1 These emerging drug classes have been proven to reduce cardiovascular events in patients with type 2 diabetes mellitus (T2DM) who are at high cardiovascular risk or have established cardiovascular disease.2 In this context, current guidelines recommend GLP-1RAs as first-line antidiabetic therapies in patients with established cardiovascular disease or high/very high cardiovascular risk.3

Semaglutide is a potent GLP-1RA used in the treatment of T2DM, with demonstrated cardiovascular benefits. It is currently available in both subcutaneous and oral formulations.4 Furthermore, the impact of high doses of semaglutide on weight loss was explored in adults with overweight or obesity in the STEP programme.5 Recently, the cardiovascular benefit of high doses of semaglutide was also observed in patients with overweight or obesity at high cardiovascular risk but without T2DM.6

Despite the proven cardiovascular benefit of semaglutide, certain safety concerns still linger. A debate surrounds the potential association between semaglutide treatment and the risk of acute pancreatitis. This point is relevant since acute pancreatitis is an unpredictable and potentially life-threatening disease.7, 8 Previous systematic reviews have explored the risk of acute pancreatitis with these drugs.9, 10, 11 However, these studies have evaluated different GLP-1RAs, involved comparisons between different hypoglycaemic drugs without including a placebo arm, did not analyse the different administration regimens of semaglutide, or failed to include the latest published studies.

The objective of this updated meta-analysis is to ascertain the risk of acute pancreatitis with the use of semaglutide, with a specific focus on evaluating the results according to the different administration regimens.