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Concerns of pancreatic damage with incretins unwarranted, says drugs regulator

The European drugs regulator has concluded there is not enough evidence to support concerns that incretins significantly increase the risk of pancreatic adverse events.

The EMA said current safety advice for prescribing the drugs is adequate, although it will consider changing the warnings in product information to make them more consistent across all gliptins and other GLP-1 based therapies.

The ruling comes following an EMA Committee for Medicinal Products for Human Use (CHMP) investigation into pancreatic adverse effects of GLP-1 (glucagon-like peptide 1) agonists, also known as incretins, after a number of reports linking the drugs to increased cases of acute pancreatitis, as well as pathology findings suggesting the drugs cause inflammation and precancerous changes in pancreatic tissue.

The CHMP found no increased concern over the risk of pancreatitis or pancreatic cancer from available clinical trials data, while the pathological study data was judged to have too many limitations, particularly due to potential of bias in patient characteristics, to draw meaningful conclusions.

The EMA says: ‘A small number of cases of pancreatitis have been reported in clinical trials. In addition, through spontaneous reports a significant number of cases have been observed, although these need to be interpreted cautiously.

‘All these medicines already carry warnings in their product information, but the CHMP considered that there would be value in harmonising the wording of these warnings across all GLP-1 based therapies so that patients and healthcare professionals receive consistent advice.’

Concerns over the potential pancreatic side effects of GLP-1 based therapies have been ramped up in recent months. Most recently, a US safety review alerted patients to a large increase in reports of pancreatic adverse events associated with the drugs.

GPs are already advised to warn patients about the potential for pancreatic side effects with GLP-1 agonists and to monitor them regularly for any signs of low-grade pancreatitis.

According to the EMA, companies marketing GLP-1 based therapies are continuing to monitor their adverse effects closely and feed back the results, while several studies including large outcomes trials are planned or ongoing to better understand the risks.

‘Marketing authorisation holders will update the risk management plans for these medicines accordingly,’ the regulator says.