In two phase 2b trials, VISTA and SOLSTICE, an oral, small-molecule, non-peptide glucagon-like peptide-1 receptor agonist (GLP-1 RA) demonstrated clinically meaningful reductions in body weight and A1C.
Melanie Davies, CBE, MBChB, MD, FRCP, FRCGP, FMedSci
“Daily oral elecoglipron demonstrated clinically meaningful weight reductions in adults living with obesity and overweight without type 2 diabetes,” said Melanie Davies, CBE, MBChB, MD, FRCP, FRCGP, FMedSci, Professor at the University of Leicester, United Kingdom, who presented data from VISTA. “As a small molecule, it’s ideal for combination treatment in the future with other small molecules.”
In SOLSTICE, elecoglipron achieved clinically and statistically significant A1C and fasting glucose reductions, said Vanita R. Aroda, MD, Director of Diabetes Clinical Research at Brigham and Women’s Hospital and Associate Professor of Medicine at Harvard Medical School.
Drs. Davies and Aroda shared these findings on Monday, June 8, during the symposium, AZD5004, A Novel Oral Small Molecule GLP-1 Receptor Agonist: Overweight/Obesity (VISTA) and Type 2 Diabetes (SOLSTICE) Phase 2 Trial Results. On-demand access to recorded presentations will be available to registered participants of the 2026 Scientific Sessions through August 10.
VISTA: Elecoglipron in Adults Living with Obesity or Overweight
VISTA was a randomized, double-blind, placebo-controlled phase 2b trial that assessed the efficacy, safety, and tolerability of elecoglipron in adults living with obesity or overweight with at least one weight-related comorbidity. A total of 310 adults were randomized to six treatment arms, including five elecoglipron doses with different titration protocols and placebo. The primary endpoints were the percent change in body weight from baseline to week 26 and the achievement of ≥5% weight loss at week 26.
No indication of a plateau in weight loss was seen at 36 weeks, and no unexpected safety signals were noted with elecoglipron, Dr. Davies reported.
“It doesn’t have food or fluid dosing restrictions, which can be so important for our patients, generally because we need convenient, effective, and safe oral treatments for people living with overweight or obesity,” she said.
There was a dose-dependent reduction in weight, starting at 2.6% with elecoglipron 5 mg and increasing to 10.5% with elecoglipron 75 mg (once-weekly titration) versus 0.6% with placebo. At 36 weeks, patients treated with elecoglipron 75 mg (once-weekly titration) achieved an average of 11.8% reduction in body weight versus 0.3% with placebo. Treatment with elecoglipron also led to meaningful improvement in blood pressure and C-reactive protein levels.
SOLSTICE: Elecoglipron in Adults with Type 2 Diabetes
SOLSTICE was a randomized, multicenter, placebo-controlled phase 2b trial that assessed the efficacy, safety, and tolerability of elecoglipron in adults with type 2 diabetes. A total of 406 patients were randomized to eight treatment arms, including six elecoglipron doses with different titration protocols, placebo, and an exploratory arm of oral semaglutide.
The primary endpoint was the change in A1C from baseline to week 26, which was met across all doses.
“A high proportion of participants receiving elecoglipron achieved the diabetes treatment targets, and I would say even from the lowest dose of 5 mg all the way to 75 mg, there were respectable improvements and achievement of targets,” Dr. Aroda said. “Elecoglipron at doses of 25 mg or higher achieved significantly greater reductions in weight compared to placebo, and the safety and tolerability profile was consistent with what we know of the GLP-1 RA class.”
Participants who received the highest dose of elecoglipron (75 mg) achieved a mean reduction in A1C of 1.9%, compared with 0.2% in the placebo group, and 1.3% in the semaglutide group.
Overall, the SOLSTICE findings support advancement of elecoglipron into the phase 3 ELUMINATE program.
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