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NEW ORLEANS — Elecoglipron, a novel oral GLP-1 receptor agonist (RA), led to significant reductions in A1c and moderate reductions in body weight in people with type 2 diabetes (T2D), according to the results of the phase 2b SOLSTICE trial. 

In addition, in the phase 2 VISTA trial, elecoglipron led to clinically meaningful weight loss and a safety profile consistent with GLP-1s in patients with overweight/obesity with at least one weight-related condition but without T2D.

Both trials were presented here at the American Diabetes Association (ADA) 2026 Scientific Sessions.

“Daily oral elecoglipron achieved clinically and statistically significant A1c and fasting glucose reductions across all doses,” said Vanita R. Aroda, MD, of the Department of Medicine, Division of Endocrinology, Diabetes and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, who presented the SOLSTICE findings.

More broadly, “development of next-generation oral small molecule GLP-1 receptor agonists might enhance patient care and support patient preferences by eliminating administration restrictions and by removing any existing barriers related to injectable delivery,” Aroda and her colleagues wrote in their paper, published concurrently in The Lancet.  

Notably, as a nonpeptide oral small molecule GLP-1 RA, similar to the recently approved oral GLP-1 orforglipron, elecoglipron’s ability to be taken without fasting or fluid restrictions is a benefit over oral semaglutide, which requires strict fasting and water-timing restrictions for optimal bioavailability, they pointed out.

SOLSTICE Trial in T2D 

In the phase 2b trial, the researchers focused on evaluating elecoglipron’s efficacy in controlling T2D. They enrolled 406 patients with T2D managed with diet and exercise alone or with monotherapy with metformin or an SGLT2 inhibitor.

The patients were randomized to either once-daily tablets of elecoglipron of 5 mg, 15 mg, or 25 mg, 1 of 3 different dose escalation regimens, or to placebo. The dose escalation regimens included target doses of 50 mg (dose escalation every 2 weeks), target doses of 75 mg (dose escalation every 2 weeks), and target doses of 75 mg (dose escalation every 4 weeks).

An exploratory group of open-label oral semaglutide titrated to 14 mg once daily for 26 weeks was also included.

The patients had a mean age of 58.4, 58% were male, their mean baseline A1c was 7.9%, and mean BMI was 34.9.

For the primary endpoint of A1c changes over 26 weeks, reductions in A1c were shown to be dose-dependent and greater in all doses vs placebo, ranging from a reduction of 0.91% with 5 mg elecoglipron to 1.88% with the highest dose of 75 mg, at the every 2-week escalation.

Meanwhile, reductions in body weight ranged from 2.54% with 5 mg elecoglipron to 7.61% with 75 mg with every 2-week dose escalation, over 26 weeks.

Increases in weight reduction based on dose were observed, with 72.3% of patients in the 75 mg elecoglipron group achieving at least a 5% weight reduction from baseline at week 26 compared with 20.2% in the placebo group meeting the same reduction threshold.

The results also showed improvements in blood pressure and liver biomarkers at week 26.

In an exploratory comparison with the oral GLP-1 receptor agonist, semaglutide, the results for the 75 mg dose of elecoglipron showed similar or greater glucose-lowering efficacy (-2.23 to -1.53 vs -1.58 to -0.98) as well as greater weight reduction at higher doses of elecoglipron at 26 weeks (7.61% vs 5.1%).

Safety and tolerability were consistent with other oral GLP-1 RAs, with the most common events including gastrointestinal events of nausea, constipation, diarrhea, and vomiting. 

Adverse events were reported in 87% of those in the 75 mg 4-week escalation group compared with 63% in the placebo group. Discontinuations related to adverse events occurred most commonly in the elecoglipron 25 mg fixed-dose group (17%) and the 75 mg every 4-week escalation group (16%). 

Patients in the study had a median duration of T2D of 6.2 years, with 22% treated only with diet and exercise, indicating that the study population “represents a relatively early [T2D] treatment population,” said Aroda.

Importantly, younger patients and those with shorter duration T2D often have higher levels of obesity, she added.

“With the greater recognition of the long-term consequences of hyperglycemia and

obesity, early treatment approaches that effectively target both glycemia and bodyweight can, in part, contribute to long-term benefits, as they have the potential to shift the longitudinal trajectory and risk of multiple long-term conditions that accompany these risk factors,” Aroda and colleagues wrote.

VISTA Trial Focusing on Weight Loss 

In the phase 2 VISTA trial, also published in The Lancet, researchers enrolled 310 patients with obesity or overweight, with at least one weight-related condition and without T2D. Study participants were randomized to receive either weekly titration of 5 mg, 15 mg, 50 mg, or 75 mg; a 75 mg group with an every 2-week titration; or to matching placebo. 

The patients, who had a mean age of 48.4 years, were 73% female, with a mean BMI of 38.2.

At week 26, with 93% of patients completing the study, the mean reduction from baseline bodyweight was between 2.6% for 5 mg elecoglipron to 10.5% with 75 mg weekly titration, compared with 0.6% placebo. 

For the co-primary endpoint of achievement of weight reductions of at least 5% at week 26, the rate was 88.8% in the elecoglipron group vs 15.6% in the placebo group.

Adverse events were similar to those observed in the SOLSTICE trial, with events ranging from 84% to 98% across elecoglipron doses compared with 84% in the placebo group, with the most common events being nausea, constipation, diarrhea, headache, and vomiting.

While the mean weight loss at the study’s endpoint of 26 week was 10.5% in the 75 mg weekly titration dose, the authors noted that the rate further increased to 11.8% at 36 weeks. 

This confirms that “a weight-reduction plateau was not reached at week 26, providing insight to durability beyond the traditional 6-month phase 2 evaluation,” said first author Melanie J. Davies, MD, of the Diabetes Research Centre, University of Leicester, and the NIHR Leicester Biomedical Research Centre, UK, in presenting the findings.

Furthermore, in addition to the 85% of participants treated with high elecoglipron doses who reached at least a 5% weight loss by the study’s cutoff of 26 weeks, 63% achieved a 10% weight loss at 36 weeks.

Overall, “we found that daily oral elecoglipron demonstrated clinically meaningful weight reductions in adults living with obesity or overweight without T2D,” Davies said.

The weight reduction observed with elecoglipron is comparable to other oral small-molecule GLP-1 RAs, although notably lower than rates seen with injectable incretin-based therapies, noted Davies. However, “the weight loss reported in this trial is expected to translate into meaningful improvements in cardiometabolic risk profiles including cardiovascular and renal risk factors, thereby conferring important health benefits in at‑risk populations.” 

‘Not Everyone Needs 30% Weight Loss’ 

In a separate overview of the study at the session, Klara Klein, MD, PhD, an assistant professor in the Division of Endocrinology and Metabolism and director of the Endocrine, Diabetes, and Obesity Clinical Research Unit at the University of North Carolina School of Medicine in Chapel Hill, said that elecoglipron, as a “middle potency drug,” will not compete with higher-potency injectable drugs such as tirzepatide, with its higher weight loss reports exceeding 20%. 

Nonetheless, it has a potentially important role as a treatment option she noted.

“While we look at population level data in these studies, [in real-world practice], we treat individuals. We treat the person that's sitting in front of us,” she said. That person might need glycemic management, or maximal weight loss, or cardiovascular risk reduction, or kidney protection, said Klein. 

“Having more options allows us to tailor” treatment to their needs. “Not everyone needs 30% weight loss, nor can they tolerate it, and having a menu of options allows us to explore the different therapies that work for the individual,” she explained.

Furthermore, “more options, more doses, and different delivery mechanisms will increase affordability and also adherence.”

On a broader level, injectable GLP-1 RAs require cold storage so “having easy-to-administer, shelf-stable medications that can be shipped and stored for the whole supply chain will enormously improve access and make it possible for us to prevent obesity-related comorbidities before they arise,” Klein said. 

Findings Justify Further Investigation 

Further commenting on the research in an editorial published along with the study, Matthias Blüher, a professor of clinical obesity research at the University of Leipzig, Leipzig, Germany, said that the two trials offer sound evidence warranting further investigation of full benefits in phase 3 trials.

“Notably, both trials provide the basis for advancing the elecoglipron study program to phase 3 trials with a longer duration, inclusion of a larger number of participants of varied ethnicities, relevant cardiometabolic outcomes, and the selection of optimal doses and dose-escalation regimens,” he wrote.

“Although the VISTA and SOLSTICE trials might not have an immediate clinical implication, they justify the need for long-term outcome trials with elecoglipron and demonstrate the increasing competition for superior efficacy and tolerability in the class of nonpeptide small-molecule GLP-1 receptor agonists.”

Blüher echoed Klein’s assertion that elecoglipron’s key importance is likely in expanding on treatment options to better meet and target the broad spectrum of patient characteristics and needs.

“As pharmacotherapy options for obesity and T2D are further expanding, there is a need to define patient profiles for tailored treatments, including the need to investigate combination therapies that take advantage of lower, better-tolerated doses of medications with complementary modes of action,” he said. 

The studies were funded by AstraZeneca. 

Davies reports relationships with Eli Lilly, Novo Nordisk, Sanofi, Kailera, AbbVie, Amgen, AstraZeneca, Biomea Fusion, Carmot Roche, Daewoong Pharmaceutical, Sanofi, Zealand Pharma, Regeneron, GSK, Innovent Bio, EktaH, Boehringer Ingelheim, and Zuellig Pharma. 

Aroda reports relationships with Amgen, Applied Therapeutics, AstraZeneca, Biomea, Boehringer Ingelheim, Corcept, Eli Lilly, Fractyl, Kailera, Novo Nordisk, Pfizer, Recordati, Rhythm, Servier, Baim Institute for Clinical Research, Mediflix, Sanofi, Structure, and Roche. 

Klein reported relationships with Antag Therapeutics, Metsera, Novo Nordisk, Roche Pharmaceuticals, vTv Therapeutics, Bayer, Boehringer-Ingelheim, Carmot, Diasome, Eli Lilly, GentiBio, and Rhythm Pharmaceuticals. 

Blüher’s disclosures include consulting and/or other relationships with Abbott, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Lilly, MSD, Novo Nordisk, Novartis, Pfizer, and Sanofi; and chairing a Clinical Trial Data Safety Monitoring Board for Boehringer Ingelheim.