Oral GLP-1 medications have the potential to increase access to therapies that can help lower blood sugar and reduce bodyweight. Today, at the American Diabetes Association's Scientific Session, Mass General Brigham physician investigator Vanita Aroda, MD, presented findings from SOLSTICE, a phase 2b randomized, placebo-controlled clinical trial that tested the oral GLP-1 RA known as elecoglipron. Results, which are published simultaneously in The Lancet, show that the drug significantly reduced blood glucose and bodyweight among people with type 2 diabetes, paving the way for oral formulations to help bridge current gaps in type 2 diabetes treatment.
"Our study's findings underscore the expanding potential of oral GLP-1 receptor agonists for people with type 2 diabetes," said Aroda, who is the Director of Diabetes Clinical Research in the Division of Endocrinology, Diabetes & Hypertension in the Mass General Brigham Department of Medicine. "To date, GLP-1 therapies have largely been limited to injectable or oral peptide formulations, each with inherent delivery and dosing constraints. Rigorous clinical trials like SOLSTICE can help us evaluate oral medications that may be just as effective for patients with diabetes while overcoming these limitations."
Elecoglipron, the oral medication tested in the SOLSTICE clinical trial, has been developed for treating type 2 diabetes. Most available GLP-1 medications need to be administered via subcutaneous injection. Semaglutide, which is approved for type 2 diabetes, can be taken in pill form but must be taken on an empty stomach first thing in the morning, with food and water restricted for 30 minutes after. One GLP-1 oral non-peptide medication, orforglipron, has been approved in the U.S. for weight management.
SOLSTICE, which was sponsored by AstraZeneca, was conducted across nine countries, including the U.S. The study enrolled 406 participants with type 2 diabetes who were randomly assigned to treatment groups. The trial tested different starting doses, dose-escalation schemes, and maintenance doses.
The researchers found that, at all dose concentrations, the medication reduced glucose levels significantly more than the placebo arm after 26 weeks. Up to 89.6% of participants who took the medication achieved an HbA1c level of 7%—the standard target goal for average blood glucose levels over the past two to three months for most adults with diabetes. That's compared to 24.9% of people who received placebo. Up to 72.3% of participants in the treatment groups achieved at least 5% weight reduction compared to 20.2% in the placebo group. Safety and tolerability were similar to other GLP-1 medications at this stage of development.
Aroda is also the principal investigator of REIMAGINE 1, a randomized controlled trial that evaluated CagriSema, a novel combination therapy that combines the amylin receptor agonist cagrilintide with the injectable form of semaglutide. Those results, presented at the ADA meeting and published in The Lancet Diabetes and Endocrinology, were also positive, with up to 87% of participants reaching the target HbA1c level of 7%.
"At the center of every one of our clinical trials is the goal of improving outcomes for patients," said Aroda. "The studies being presented at this year's meeting highlight how essential carefully designed trials are for evaluating new therapies, refining existing approaches, and ensuring that advances in science translate into safer, more effective care for people living with diabetes."
Authorship: In addition to Aroda, authors include Melanie J Davies, Jill Maaske, Marcus Millegård, Víctor López Juan, Jens Aberle, Andreea Ciudin, Rory J McCrimmon, Olof Eklund, Judy L Shih, Mikaela Sjostrand, Donna Zarzuela, and Julio Rosenstock.
Disclosures: Aroda declares institutional contracts from Amgen, Applied Therapeutics, AstraZeneca, Biomea, Boehringer Ingelheim, Corcept, Eli Lilly, Fractyl, Kailera, Novo Nordisk, Pfizer, Recordati, Rhythm and Servier; and consulting fees from Baim Institute for Clinical Research, Mediflix, Sanofi, and Roche. Additional author disclosures can be found in The Lancet.
Funding: AstraZeneca.
Paper cited: Aroda VR et al. "Elecoglipron, an oral small molecule GLP-1 receptor agonist in adults with type 2 diabetes (SOLSTICE): a phase 2b, multicentre, randomised, placebo-controlled trial" The Lancet DOI: 10.1016/S0140-6736(26)00802-0
