First Time: Orally Available GLP-1 Agonist More Effective than DPP-IV Inhibitor

With the participation of researchers from the Paul Langerhans Institute Dresden (PLID), a GLP-1 receptor agonist in the form of tablets was compared for the first time with the most common second-line therapy of T2D, a DPP-IV inhibitor. The investigations were carried out in parallel in Japan, France, England, Mexico, Denmark, the USA and Germany as part of the international, randomised double-blind study PIONEER-3. The results are considered to point the way for future therapy of type 2 diabetes.


Patients with diabetes still die 2-3 times more frequently from cardiovascular diseases than people without diabetes. Against this background, so-called incretin analogues have been developed in recent years, i.e. drugs that, like the intestinal hormone GLP-1, lead to the release of insulin in the beta cells of the pancreas and at the same time reduce the feeling of hunger in the brain. "Unfortunately, these drugs, like all peptide-based drugs due to their chemical structure, have to be administered by subcutaneous injection and cannot be taken orally as tablets," said Prof. Dr. Andreas Birkenfeld, PLID, co-author of the study. "Fortunately, the GLP-1 receptor agonist (GLP-1RA) semaglutide is now available as a tablet in combination with an absorption enhancer for the first time."

The 78-week PIONEER-3 study compared 1864 adults with diagnosed type 2 diabetes who took either metformin (with or without sulfonylurea), oral semaglutide in three different doses or sitagliptin (100 mg/d). Oral semaglutide was found to be superior to sitagliptin (at the highest dose) in terms of blood glucose lowering and body weight reduction. The most frequent side effects of GLP-1RA were gastrointestinal effects such as nausea. Although these were more common with semaglutide than with sitagliptin, they are already known from other GLP-1RA and in many cases temporary, so that GLP-1RA are considered safe.

Original publication:
Rosenstock J, Allison D, Birkenfeld AL, Blicher TM, Deenadayalan S, Jacobsen JB, Serusclat P, Violante R, Watada H, Davies M; PIONEER 3 Investigators. Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea: The PIONEER 3 Randomized Clinical Trial.   JAMA. 2019 Mar 23. doi: 10.1001/jama.2019.2942. [Epub ahead of print]

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