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expert reaction to two studies looking at AstraZeneca’s GLP 1 pill, elecoglipron, for reducing weight and lowering blood-sugar in adults with and without type 2 diabetes

Two studies published in The Lancet look at AstraZeneca’s GLP-1 pill elecoglipron for weight loss and lowering blood-sugar in adults with and without type 2 diabetes. 

 

Prof Martin Whyte, Professor of Metabolic Medicine, University of Surrey, said:

“Two new Phase 2 randomised trials – VISTA (in obesity without diabetes) and SOLSTICE (in type 2 diabetes) – highlight the emergence of ‘small‑molecule’ GLP‑1 receptor agonists.  These are tablets that unlike peptide-based injectables, do not require cold storage or injection, potentially widening access, and acceptance.  In VISTA, people living with overweight or obesity achieved around 10–12% weight loss at six to nine months, with up to 90% reaching clinically meaningful reductions of at least 5%.  In SOLSTICE, those with type 2 diabetes experienced meaningful glucose lowering alongside weight loss of around ~5–7%.

“While these effects do not yet fully match the most potent injectable therapies, they are clinically very effective, with much greater convenience.  From a practical perspective, a once‑daily tablet could enable earlier and wider use of GLP‑1–based treatment, including in settings where injectables are less feasible.  Studies are also evaluating small molecule GLP-1 drugs as a means of transitioning off injectables.  As expected, VISTA and SOLSTICE showed that nausea and diarrhoea were common but generally manageable.  Overall, these findings suggest small‑molecule GLP‑1 therapies could broaden access to effective treatments, although longer‑term data will be key to confirm durability and safety.

“The studies were of high-quality and across a number of countries.  The main limitation is that they were Phase 2 trials (i.e. smaller and shorter than a phase 3 trial).  There will be Phase 3 trials following, I am sure.”

 

Dr Marie Spreckley, Prevention of Diabetes and Related Metabolic Disorders in High Risk Groups, University of Cambridge, said:

“These are well-conducted phase 2 randomised, placebo-controlled trials that provide early evidence for elecoglipron, a once-daily oral small-molecule GLP-1 receptor agonist.  The obesity trial enrolled 310 participants and followed them for 36 weeks, while the type 2 diabetes trial enrolled 406 participants and followed them for 26 weeks.

“In adults with obesity or overweight without diabetes, elecoglipron produced dose-dependent weight loss, with average weight reductions of up to 10.5% at 26 weeks and 11.8% at 36 weeks in the highest-dose group.  In adults with type 2 diabetes, elecoglipron reduced HbA1c by up to 1.88 percentage points and produced average weight loss of 7.7% at 26 weeks.  These findings show substantial improvements in both weight and glycaemic control and support further investigation in phase 3 trials.

“One potentially important feature of elecoglipron is that it is taken orally without food or fluid restrictions.  If future studies confirm its efficacy and safety, this could offer a convenient alternative for some patients and could help overcome some practical barriers associated with injectable treatments or oral therapies that require specific dosing conditions.

“The safety profile observed in these trials was broadly consistent with the GLP-1 receptor agonist class, with gastrointestinal side effects such as nausea, constipation, diarrhoea and vomiting reported most commonly.

“However, it is important to recognise that these are phase 2 studies and were primarily designed to compare elecoglipron with placebo.  Although the diabetes trial included an exploratory semaglutide arm, neither study was designed or powered to make definitive comparisons with currently available GLP-1 receptor agonists.  Larger and longer phase 3 trials will therefore be needed to confirm the durability of these effects, establish longer-term safety and tolerability, and determine its place within the growing range of obesity and diabetes treatments.

“Notably, weight loss in the obesity trial continued through the end of follow-up, and a clear weight-loss plateau was not observed during the study period.  Whether these effects are sustained over longer periods, and how they compare with existing therapies, remains to be established.

“Overall, these findings support the continued clinical development of elecoglipron and add to the growing evidence supporting the development of oral GLP-1 receptor agonists for obesity and type 2 diabetes.”

 

 

Paper 1: ‘Elecoglipron, an oral small molecule GLP-1 receptor agonist in adults with obesity or overweight (VISTA): a multicentre, phase 2, randomised, placebo-controlled clinical trial’ by Melanie J Davies et al. will be published in the Lancet at 21:15 UK time on Monday 8 June 2026, which is when the embargo will lift.

 

DOI: 10.1016/S0140-6736(26)00748-8

 

Paper 2: ‘Elecoglipron, an oral small molecule GLP-1 receptor agonist in adults with type 2 diabetes (SOLSTICE): a multicentre, phase 2b, randomised, placebo-controlled trial’ by Vanita R Aroda et al. will be published in the Lancet at 21:15 UK time on Monday 8 June 2026, which is when the embargo will lift.

 

DOI: 10.1016/S0140-6736(26)00802-0

 

 

 

Declared interests

Prof Martin Whyte: “I have previously received consultation fees from Boehringer and NovoNordisk and speaker fees from AstraZeneca.”

Dr Marie Spreckley: “Dr Marie Spreckley is a postdoctoral researcher at the University of Cambridge specialising in obesity, nutrition and weight management research.  She declares no personal financial interests, consultancy agreements, advisory roles, speaker fees, stock ownership, honoraria, or pharmaceutical industry employment related to incretin-based therapies.”

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