John Buse, MD: PIONEER 7 Trial of Oral Semaglutide

With an FDA decision expected in September, the results of the Pioneer trials were among the most anticipated presentations at the American Diabetes Association (ADA) 2019 Scientific Sessions in San Francisco, CA.

PIONEER 7 was one of several Pioneer trials presented at ADA 2019 and it examined the effect and safety of flexible dose adjustment of oral semaglutide versus sitagliptin in patients with type 2 diabetes.

John Buse, MD, PhD, led the trial, which found that flexible dose adjustment with oral semaglutide was superior in glycemic control and in weight loss at 52 weeks. Unlike other PIONEER trials, which sought to compare efficacy and safety of oral semaglutide in 14mg doses compared to other leading treatments, PIONEER 7 examined a flexible dosage of oral semaglutide in patients.

At week 52, the cohort receiving flexible doses of oral semaglutide had greater average weightloss, a higher percentage of patients with HbA1c of 7 or less, and a greater change from baseline HbA1c than patients in the sitagliptin group. At ADA 2019, Buse sat down with MD Magazine® to discuss PIONEER 7, oral semaglutide, and the clinical impact of the findings.

MD Mag: What were the results of the PIONEER 7 trial?

Buse: So, the thing is different about Pioneer 7 than the other trials with oral semaglutide we tried to look at a way that semaglutide might be used in the community and so instead of titrating up from 3 milligrams to 7 milligrams to 14 milligrams just in a lockstep monthly basis, we decided to do a slower titration in hopes that that would enhance tolerability and we only had the patients increase the dose if they needed greater a1c reduction. So, if their a1c was greater than 7% or if they tolerated the drug well. So, if they had persistent nausea over the three last days before the titration step would only occur no titration occurred or even back titration occurred.

So, what we showed in the trial was that oral semaglutide with this flexible titration approach was superior to sitagliptin with regards to the proportion of patients achieving an a1c less than 7 and weight loss. That's not unexpected there are other head-to-head trials versus sitagliptin that had been done and I think you know I would characterize overall is that we were in a way a little bit disappointed that this more flexible system didn't even give us better results, that more people with a slower titration would be able to get to the full dosing level.

I think part of that is because we didn't allow titration for patients who already achieved an a1c of less than 7. So, in that way we kind of minimized thenpotential effect. I think the bottom line is that in patients who tolerate the 3 milligram dose of oral semaglutide in general they are going to tolerate the 7 and 14 milligram dose. With the bigger dose we get more weight loss and you know that's an opportunity for patients.