ADA: AZ reveals oral GLP-1 data in obesity, diabetes

AstraZeneca is preparing to move its oral GLP-1 agonist elecoglipron into a phase 3 programme in obesity and type 2 diabetes, after reporting encouraging mid-stage results.

The results of the phase 2b VISTA and SOLSTICE studies, presented at the ADA congress in New Orleans and published in The Lancet, provide the first evidence that AZ may have a rival to the two currently-approved oral GLP-1 agonists – Novo Nordisk's Wegovy (semaglutide) and Eli Lilly's Foundayo (orforglipron) – which started to roll out into the market earlier this year.

Data from the 310-subject VISTA trial revealed average weight reductions of up to 10.5% at 26 weeks and 11.8% at 36 weeks in the highest-dose group (75 mg) in adults with obesity or overweight and at least one weight-related comorbidity. By that time point, nearly 40% of patients on that dose had lost at least 15% of their body weight.

In SOLSTICE, which enrolled 404 participants with T2D and followed them for 26 weeks, elecoglipron reduced A1C levels by up to 1.9% with an average weight loss of 7.7%. The majority of participants receiving elecoglipron 75 mg achieved guideline-recommended blood glucose target, with 90% reaching an A1C level of less than 7% and 85% attaining 6.5% or lower.

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, but treatment discontinuations due to adverse drug reactions were "infrequent," according to AZ.

The discontinuation rate was 8% with the 75 mg dose in VISTA, and 11% to 16% in SOLSTICE, depending on the speed at which doses were titrated up, and AZ said its phase 3 trials will take that into account with a dose-escalation regimen that will "further enhance the tolerability profile."

The phase 3 programme will include EMBOLD trials in overweight and obesity, with or without T2D, and the ELUMINATE programme that will test elecoglipron as a monotherapy and with AZ's SGLT2 inhibitor Farxiga (dapagliflozin) in people with T2D. Additional studies will focus on long-term cardiovascular and kidney outcomes, said AZ.

Commenting on the studies, Dr Marie Spreckley – a specialist in diabetes and related metabolic disorders at the University of Cambridge – said 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," she added.

The current oral GLP-1s both have restrictions on their labelling. Wegovy has to be taken first thing in the morning on an empty stomach, half an hour before eating or drinking, while Foundayo should not be taken alongside oral birth control or the widely used cholesterol-lowering drug simvastatin.

"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," said AZ's head of biopharma R&D, Sharon Barr.

Its pipeline also includes weekly injectable selective amylin receptor agonist AZD6234 and weekly injectable dual GLP-1/glucagon receptor agonist AZD9550, both in mid-stage testing, along with a battery of additional candidates stemming from its recent $18.5 billion R&D alliance with China's CSPC Pharma.