Body Weight Reduction
Participants on 50 mg amycretin lost an average of 10.4% of their body weight (estimated treatment difference vs placebo, –9.2; 95% CI, –12.0 to –6.5), whereas those on 2 × 50 mg amycretin lost 13.1% of their body weight (estimated treatment difference vs placebo, –11.8; 95% CI, –14.6 to –9.0). Placebo group participants lost 1.2% of their body weight over the 12 weeks.
Although no plateauing of weight loss was seen, said Dr. Gasiorek, it is important to consider the relatively short treatment duration and the limited time on the final dose, which could potentially introduce bias.
To date, weight loss medications based on GLP-1 RA technology are injectables. A combination of the injectable amylin analogue cagrilintide and the GLP-1 RA semaglutide is also being explored as a subcutaneous treatment solution.
In a comment, Martin Holst Lange, MD, PhD, executive vice president of development at Novo Nordisk, said that “amycretin is the first treatment to harness the two distinct biological pathways stimulated by amylin and GLP-1 in a single molecule.”
The safety and tolerability profiles and the magnitude of weight loss support further development of amycretin in patients with overweight or obesity, said Dr. Lange, who noted that the company was awaiting data from the ongoing phase 1 trial with subcutaneous amycretin, expected in 2025.
Having heard the presentation, co-moderator Timo Müller, PhD, professor at Ludwig Maximilian University of Munich, Germany, gave a considered response. “The drug was relatively well tolerated, with the typical GLP-1–induced GI [gastrointestinal] adverse effects being the most frequently reported.”
But he pointed out that questions remain. “We still need to know whether, at the given dose, the drug outperforms best-in-class drugs like semaglutide or tirzepatide at the highest approved doses. Furthermore, it warrants clarification if and to what extent the activation of the amylin receptor contributes to the shown effect and if and to what extent the glycemic benefits result from activation of the glucagon receptor (amylin improved glycemia by decreasing the secretion of glucagon). In any way, the current data remain friendly and support phase 2 development.”
Oral Meds Could Bring Down Cost
Commenting on the data, Nerys Astbury, PhD, associate professor of diet and obesity at Nuffield Department of Primary Health Care Sciences, University of Oxford, England, said, “It is important to note that whilst the participants in this trial did lose weight over the 12-week study — and this was statistically more weight than in the placebo group — this study was not designed or powered to detect differences in body weight over longer periods of time.”
If the results are confirmed in future studies, amycretin might widen the treatment options and introduce competition, probably bringing down the costs in the longer-term, said Dr. Astbury, who welcomes the prospect.
“It is possible that some people might find the oral medications more acceptable than the injectable GLP-1 agonists currently available,” she said. And the current options are expensive, “which raises challenges to a taxpayer-funded health system like the NHS [National Health Service].”
“Furthermore, if the growing number of oral obesity medications prove safe, tolerable, and effective ... they are likely to significantly reduce the risks of developing many complications of obesity.”
Naveed Sattar, MD, professor of cardiometabolic medicine and honorary consultant, University of Glasgow, Scotland, agreed. “The more medicines coming forward to treat obesity, the better,” he said. In particular, oral medications would be more easily available, and cheaper, “for the many millions around the world struggling with obesity and its complications.”
Dr. Gasiorek declares she is an employee of and a shareholder in Novo Nordisk. Dr. Astbury declares no financial disclosures. Dr. Sattar declares having consulted for several companies that make diabetes medicines but also contributed to several lifestyle trials. For Novo Nordisk, he has consulted for the company on advisory boards, but not on any of their weight loss drug trial committees, and he is on the steering committee for the ZEUS trial, which is not a weight loss trial product but an anti-inflammatory. He does not have any shares for any product in health etc. He declares consulting fees and/or speaker honoraria from Abbott Laboratories, Afimmune, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceuticals, Janssen, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi, and grant support paid to his university from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche Diagnostics. Dr. Müller received financial support or an honorarium from Novo Nordisk, Merck, Eli Lilly, Boehringer Ingelheim, and Mercodia; he further holds stocks at Novo Nordisk and Eli Lilly and is cofounder of Bluewater Biosciences.
A version of this article first appeared on Medscape.com.