Intended for healthcare professionals

Incretin mimetics


Incretin therapies—glucagon-like peptide-1 (GLP-1) agonists and dipeptidylpeptidase-4 (DPP-4) inhibitors—looked as if they might change the face of type 2 diabetes. Their dual action of switching on insulin and suppressing glucagon to help control blood glucose has been hailed as the biggest breakthrough since the discovery of insulin. And they may soon also be licensed for treating obesity.

But a BMJ investigation published in June 2013 and accompanying Channel 4 Dispatches programme found growing safety concerns linked to the drugs’ mechanism of action and asked why doctors and patients have not been told.

Concerns held by some specialists about the potential side effects emerged after the FDA and the European Medicines Agency announced in March 2013 that they would launch a review into whether the drugs may cause or contribute to the development of pancreatic cancer.

The saliva of the desert dwelling Gila monster (pictured) was the source for the first GLP-1 analogue on the market, exenatide. A heavy slow moving lizard, it eats once or twice a year, and uses the secretion of its salivary hormone exendin-4—which displays similar properties to GLP-1—to induce proliferation of its pancreas and gut to assimilate a meal.

This page links to the investigation and accompanying commentaries, a BMJ video about the science behind the story, and a timeline showing what happened when. You can also see the correspondence trail between BMJ investigations editor Deborah Cohen and the drug companies with an interest in developing insulin mimetic drugs.

See also