GLP-1 agonists: moving towards disappointment?

Who remembers (how could you forget?) the slow drip, drip, drip of evidence that TZDs weren’t so wonderful as we had at first thought after all? I do because I had my head so firmly in the sand I could practically see all the way through to Australia (yes, yes, I know New Zealand is actually the antipode of the UK but it just doesn't work as well).

Now even I accept that pioglitazone should be used with great caution in patients with no history of heart failure, who aren’t post menopausal women (osteoporotic fracture risk) and who aren’t about to get a bladder cancer.

Could we be going the same way with the GLP-1 agonists? I do hope not. We are desperate for new drugs for people with T2DM and weight issues. Frankly, we are desperate for anything that isn’t insulin, metformin, or a sulphonylurea! So we have fallen on exenatide, liraglutide and the like and some of us have fallen on the DPP-IV inhibitors as well with unbridled enthusiasm.

However, I’ve started getting bad déjà vu: first GLP-1 agonists cause pancreatitis … “so what, there’s no such thing as a completely safe drug” we all chorus. Then we remember that there is as yet no long-term outcome data showing reduced mortality, reduced CV event rates and the like … “give it time, that’ll come” we all chant.

Then there are case reports of GLP-1 induced renal failure … “they probably already had CKD, the prescribing physicians should have been more careful” we console our selves.

But now in a Diabetes study of eight subjects, seven treated with DPP-IV inhibitors and 1 with a GLP-1 agonist, the first evidence in humans of exocrine and endocrine pancreatic proliferation and dysplasia has emerged … “It’s only one study, it’s only eight subjects, only one had received a GLP-1 agonist” I find myself saying, but how much longer can I keep re-assuring myself and my patients for?

I think we've been here before. 

Tags for this article: GLP1 agonists

The author - Dr Jeremy Turner

Jeremy Turner A consultant diabetologist and endocrinologist in Norfolk, and author of Diabetes Bible

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My blog expresses my personal views on the rapidly advancing field of diabetes. It is aimed at fellow physicians and is not offering medical advice to readers. I will not respond to requests for clinical advice. If you have health concerns please contact your GP or specialist.

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