Dipeptidyl peptidase-4

Well, Abstract 1445, presented by Ibis and colleagues, brings some Trigand filings.

Using the TriNetX database, researchers compared GLP-1 receptor agonists with DPP-4 inhibitor in patients with rheumatoid arthritis and type 2 diabetes.

After propensity score matching, more than 3,000 patients were included with three years of follow-up.

And the results were striking.

15 instances in total across 134,000 patients.

And we're talking about 10 people versus five people on SGLT2 inhibitors, DPP4 inhibitors.

But I think the number to hone in on is the 15 total cases, the 10 versus five.

It is extremely rare that this is happening.

So I want you to hear this from me.

A large 2025 database study found more shingles and more cold sores on a GLP-1 than on a DPP-4 inhibitor.

That's stuff like Genuvia.

Shingles was about 29% more likely and cold sore is about 39% more likely.

That takes us nicely to autoimmune diseases.

You'll see a lot of headlines that GLP-1s raise the risk of autoimmune diseases like rheumatoid arthritis, psoriasis, or thyroiditis.

Those come from large database studies that found risks 8% to 30% higher on a GLP-1 than on a DPP-4 inhibitor.

But the DPP-4 inhibitors are not a neutral comparison.

So that was the first clinical evidence.

But, you know, at the same time, Other groups, and particularly Novo Nordisk, were working with the natural peptide and trying to see what could be done to rescue that, and discovered that the big thing was to attach a fatty acid to the molecule and make it bind to albumin in the circulation, avoid elimination in the kidneys, and then also stabilize it towards the DPP4 enzyme that we had demonstrated was completely deleterious to the hormone.

It was ready for a long time, but it was then approved in 2009 and

2010.

that? Yes, to see whether hospitalization is disruptive to the continued use of these medicines.

To do that, we also studied another common tablet known as DPP-4 inhibitors used for type 2 diabetes that don't have those same concerns.

That's Tamara Mildred.

So what they did was they used dispensing data, in other words, data from pharmacies about whether or not they dispensed these drugs and hospitalization data, so linking hospitalization to dispensing data over a period of 90 days to link these two drugs to see what the 90-day use looked like.

And so we did indeed find that people using these medicines were 83% more likely to discontinue the medicine around the time of hospitalisation compared with other times.

And surprisingly, we weren't expecting to have a positive finding for the other medicine without those safety concerns.

There was a 55% increased risk of discontinuing the DPP-4 inhibitor around the time of hospitalisation compared to other times, suggesting that this is not just limited to SGLT2 inhibitors, which may be paused around the hospitalisation, but potential implications for other medicines.

You've already said earlier that there's a risk to discontinuation.

And then the authors bring in another layer that I find really interesting.

Certain oral bacteria produce DPP4-like enzymes.

DPP4 is relevant because the human DPP4 enzyme degrades endogenous GLP-1.

So now we're starting to ask whether there could actually be a bidirectional relationship between incretin signaling and the oral microbiome.

Things look pretty similar.

Best study, which used three national insurance databases, found about 1.6 fewer flare-ups per 100 patients every year on a GLP-1 than on a DPP-4 inhibitor.

That's medicines like Genuvia.

And also the SDLT2 pills inhibitors did at least as well.

So that comes up because of the cancer headlines that generally have surrounded GLP-1s.

The short answer is that there is no sign that GLP-1s raise lung cancer risk.

Two large database studies found less lung cancer on a GLP-1 than on a DPP-4 inhibitor.

But that gap was about two cases per 1,000 patients over a period as long as 10 years.