Elecoglipron Advances to Phase III in AstraZeneca Trials

Positive results from the VISTA and SOLSTICE Phase IIb trials of elecoglipron, an oral small molecule GLP-1 receptor agonist (GLP-1 RA), unlock the next chapter in AstraZeneca's ambition to develop therapies that improve cardiometabolic and kidney health and reduce weight-related complications. These results, presented today at the 2026 Scientific Sessions of the American Diabetes Association (ADA) and simultaneously published in The Lancet, mark an important step in building AstraZeneca's differentiated weight management portfolio of monotherapies and combinations, supported by the Company's broad CVRM pipeline and global commercial expertise. AstraZeneca is advancing elecoglipron into an extensive Phase III programme in obesity and type 2 diabetes, including cardiovascular and kidney outcome trials.

In VISTA (n=310), adults with obesity or overweight and at least one comorbidity receiving elecoglipron (75mg) achieved a clinically meaningful and statistically significant average reduction in body weight of 10.5% at 26 weeks compared to 0.6% with placebo, a dual primary endpoint. Weight loss in participants receiving elecoglipron did not plateau, reaching 11.8% at 36 weeks (75mg) versus 0.3% with placebo. The trial also met the dual primary endpoint of proportion of participants achieving at least 5% weight loss at 26 weeks, with up to 88.8% of participants receiving elecoglipron achieving this threshold. In addition, elecoglipron showed clinically meaningful improvements in several exploratory analyses of cardiometabolic risk factors including lower blood pressure and C-reactive protein levels, a marker of systemic inflammation.

In SOLSTICE (n=404), adults with type 2 diabetes receiving elecoglipron (75mg) achieved a clinically meaningful and statistically significant average reduction in HbA1c of 1.9% from baseline at 26 weeks compared to 0.2% with placebo, the trial's primary endpoint. The majority of participants receiving elecoglipron (75mg) achieved guideline recommended glycaemic targets by 26 weeks, with 90% reaching an HbA1c of less than 7% and 85% reaching an HbA1c of 6.5% or lower. Elecoglipron (75mg) also demonstrated a clinically meaningful average reduction in body weight of 7.7% at 26 weeks compared to 1.7% with placebo.

The safety profile of elecoglipron was consistent with the GLP-1 RA class. Adverse events were predominantly gastrointestinal and of mild to moderate severity. In VISTA, the most common adverse events with elecoglipron (75mg) compared to placebo respectively were nausea (55%, 20%), constipation (41%, 6%), diarrhoea (35%, 25%) and vomiting (29%, 5%). In SOLSTICE, the most common adverse events with elecoglipron (75mg) compared to placebo were nausea (37%, 3%), constipation (29%, 4%), diarrhoea (21%, 15%) and vomiting (18%, 1%). Adverse events leading to discontinuation were infrequent in both trials and no liver safety signals were observed. In participants with type 2 diabetes (SOLSTICE), hypoglycaemia was uncommon, and no serious adverse events or discontinuations were attributed to hypoglycaemia.

The Phase II tolerability data have informed the dose escalation schedule in the Phase III programme to further enhance the tolerability profile.

Melanie Davies, Professor of Diabetes Medicine at University of Leicester, Honorary Consultant Diabetologist at University Hospitals of Leicester NHS Trust and Principal Investigator for VISTA said: "Despite huge progress in the field of obesity management, significant opportunity remains to deliver broader, sustainable and more meaningful health benefits for the billions of people living with obesity or weight-related complications.The VISTA results show that people receiving once-daily oral elecoglipron achieved significant weight loss as well as lower blood pressure and systemic inflammation, demonstrating its potential to treat both obesity and its related complications."

Vanita Aroda, Director of Diabetes Clinical Research at Brigham and Women's Hospital, Associate Professor at Harvard Medical School and Principal Investigator for SOLSTICE, said: "In the SOLSTICE trial, the significant HbA1c and weight loss results achieved with elecoglipron show its potential to become an important treatment option for people with type 2 diabetes. As many as eight of every 10 patients who received elecoglipron reached their guideline-recommended glycaemic targets, which we know are linked with better outcomes and long-term health."

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca said: "Our ambition is to have a portfolio that can tackle many of the cardiovascular, renal and metabolic diseases that are leading causes of death worldwide. The progression of elecoglipron is an important step in delivering a differentiated weight management portfolio, offering monotherapies and combinations, designed to address the biological complexity of obesity and comorbidities that can be tailored to individual needs, enabling people to live healthier lives. These results give us confidence as we kick off our extensive Phase III programme."

The elecoglipron Phase III programme includes the EMBOLD Phase III trials which will evaluate elecoglipron as treatment for people with obesity or overweight, with and without type 2 diabetes. The ELUMINATE Phase III trials will evaluate elecoglipron, as monotherapy and in combination with dapagliflozin, as treatment for people with type 2 diabetes. Additional outcome trials will focus on long-term cardiovascular and kidney outcomes.

These results were presented today during a Symposium at the ADA's 2026 Scientific Sessions in New Orleans and simultaneously published in The Lancet (VISTA, SOLSTICE).

Notes

Obesity and weight-related comorbidities
Nearly three billion people worldwide are estimated to be living with obesity or overweight (BMI ≥ 27 kg/m²), and with rates rapidly rising, effective, accessible management options are urgently needed to address individual patient goals and the soaring impact on chronic disease and more broadly, healthcare systems.¹ Obesity is recognised as a chronic, relapsing, multifactorial disease that contributes to over 200 complications, with cardiovascular-renal-metabolic diseases among the most common comorbidities.² Approximately 60% of people diagnosed with obesity or overweight have at least one comorbidity.^3,4

Type 2 diabetes
Type 2 diabetes is a complex, chronic metabolic condition that extends beyond blood sugar regulation, frequently involving multiple organ systems and elevating the risk of cardiovascular disease, kidney disease and hypertension. Almost 90% of people newly diagnosed with type 2 diabetes are living with either overweight or obesity, which are both key drivers of the condition.⁵ The global diabetes prevalence rate in adults is estimated to be over 10% and is projected to rise to 643 million by 2030 and 783 million by 2045.⁵

VISTA trial
The VISTA Phase IIb trial was a global, randomised, parallel-group, double-blind, study evaluating the efficacy, safety and tolerability of elecoglipron compared to placebo in adults with obesity or overweight with at least one weight-related comorbidity. Elecoglipron was evaluated at fixed doses of 5mg and 15mg, and regimens of 50mg (reached following dose escalation every four weeks) and 75mg (reached following dose escalation either weekly or every two weeks). Elecoglipron, regardless of dose, and placebo were administered once daily as oral tablets. All participants received standardised diet and physical activity advice alongside study treatment. The trial was conducted across seven countries and enrolled 310 participants (mean baseline weight 106.9kg).

The trial's co-primary endpoints were percent change in body weight and the proportion of participants achieving at least 5% weight loss, both measured from baseline to 26 weeks. The total treatment duration of the trial was 36 weeks. The trial used the efficacy estimand to measure the full weight-loss potential of elecoglipron in patients who followed treatment as directed, providing the biological data needed to confirm optimal dosing for Phase III trials.

ⁱDose-escalated every four weeks until reaching 50mg once daily
ⁱⁱDose-escalated weekly until reaching 75mg once daily
ⁱⁱⁱDose-escalated every two weeks until reaching 75mg once daily

SOLSTICE trial
The SOLSTICE Phase IIb trial was a global, randomised, parallel-group, double-blind study evaluating the efficacy, safety and tolerability of elecoglipron compared to placebo in adults with type 2 diabetes. An open-label oral semaglutide arm was included for exploratory comparison. Elecoglipron was evaluated at fixed doses of 5mg, 15mg and 25mg, and regimens of 50mg (reached following dose escalation every two weeks) and 75mg (reached following dose escalation either every two or four weeks). Elecoglipron, regardless of dose, placebo and semaglutide were administered once daily as oral tablets. The trial was conducted in nine countries and enrolled 404 participants (mean baseline HbA1c 7.9%).

The trial's primary endpoint was change in HbA1c measured from baseline to 26 weeks. The trial used the efficacy estimand to measure the full glycaemic control potential of elecoglipron in patients who followed treatment as directed, providing the biological data needed to confirm optimal dosing for Phase III trials.

ⁱDose-escalated every two weeks until reaching 75mg once daily
ⁱⁱDose-escalated every four weeks until reaching 75mg once daily
^IiiOpen-label oral semaglutide titrated to 14mg once daily
^ivIn participants with HbA1c ≥7% at baseline

Elecoglipron
Elecoglipron is an investigational oral, once-daily, small molecule GLP-1 receptor agonist that mimics the natural GLP-1 hormone. It targets receptors in the gut and hypothalamus as part of the brain-gut axis to regulate food intake and metabolic function. Elecoglipron has potential to expand treatment options for many patients due to easier scalability compared to peptides and no food or fasting restrictions. AstraZeneca is exploring elecoglipron as monotherapy and in combinations to offer treatment regimens that can potentially help patients manage excess weight, its health complications and other interrelated diseases. AstraZeneca is also assessing the potential of elecoglipron in indications beyond type 2 diabetes and weight management.

AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca's main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys, liver and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection by slowing or stopping disease progression, and ultimately paving the way towards regenerative therapies. The Company's ambition is to improve and save the lives of millions of people, by better understanding the interconnections between CVRM diseases and targeting the mechanisms that drive them, so we can detect, diagnose and treat people earlier and more effectively.

AstraZeneca
AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Disease, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide.