Obesity drugs mkt is expanding beyond GLP-1 to amylin and glucagon

Professor W. Timothy Garvey has presented an individualized approach in obesity treatment strategy at ICOMES

Therapeutics can be used depending on required weight-loss range, comorbidities, and tolerability

The obesity drug market, dominated by GLP-1 receptor agonists, is diversifying toward using novel hormonal pathways such as amylin and glucagon.

In the future, rather than administering the same drug to everyone with obesity, treatment strategies could evolve into tailored approaches that select GLP-1-based therapeutics, amylin agonists, and dual or triple agonists based on comorbid complications, required weight-loss range, and tolerability.

W. Timothy Garvey, Professor of the Department of Nutrition Sciences at the University of Alabama at Birmingham (UAB), attended the International Congress on Obesity and Metabolic Syndrome (ICOMES 2026) organized by the Korean Society for the Study of Obesity (KSSO) at the Conrad Hotel in Yeouido on the 4th, where he delivered a presentation titled "Incretin Targets to Multi-Hormonal Approaches: The Role of Amylin and Glucagon" and introduced future directions in the development of next-generation obesity therapies.

Professor Garvey distinguished newly emerged obesity drugs such as 'Wegovy (semaglutide)' and 'Mounjaro (tirzepatide)' from conventional agents, calling them "second-generation therapies." While conventional obesity treatments showed an average weight-loss efficacy of 10% or less, recent therapeutics have achieved an average reduction of 15% or more.

However, Professor Garvey noted that the significance of second-generation therapeutics does not lie merely in increasing weight-loss range. Professor Garvey explained that greater weight reduction expands the scope for preventing or improving various obesity-related complications. Therefore, obesity management should focus on improving patient health rather than body weight alone.

W. Timothy Garvey, Professor of the Department of Nutrition Sciences at the University of Alabama at Birmingham (UAB), attended the International Congress on Obesity and Metabolic Syndrome (ICOMES 2026) organized by the Korean Society for the Study of Obesity (KSSO) at the Conrad Hotel in Yeouido on September 4.

Expanding to amylin and glucagon…Diversification of targets for novel obesity drugs

Global development of obesity treatments is broadening its targets beyond the single GLP-1 pathway to diverse hormones regulated by nutritional status, including amylin, GIP, glucagon, and PYY.

In addition to single agonists, dual agonists targeting both GLP-1 ·glucagon triple agonists, are currently under development. This approach aims to maximize weight-loss efficacy by combining distinct mechanisms of action.

Boehringer Ingelheim's GLP-1·glucagon dual agonist survodutide demonstrated a weight-loss rate of 16.6% at week 76 in the maximum-dose 6 mg cohort, based on the efficacy estimand (assuming treatment adherence), in the Phase 3 SYNCHRONIZE-1 trial. Based on the treatment-regimen estimand, which reflects treatment discontinuations and other variables, the rate was 13.0%.

However, tolerability remains a challenge. The proportion of patients in the 6 mg group who discontinued the investigational drug due to adverse events was approximately 20%, and gastrointestinal adverse events such as nausea and vomiting were also relatively frequent.

Professor Garvey pointed out, "A discontinuation rate of 20% is concerning," noting that the burden of gastrointestinal adverse events was greater than in prior GLP-1 clinical trials. Conversely, he attributed positive significance to the findings showing reductions in liver fat and liver stiffness.

Eli Lilly's GLP-1·GIP·glucagon triple agonist retatrutide achieved a weight loss rate of 28.3% at the maximum dose of 12 mg based on the efficacy estimand in the Phase 3 TRIUMPH-1 trial. The 9 mg and 4 mg doses achieved reductions of 25.9% and 19.0%, respectively.

Describing the extent of weight reduction observed at the maximum dose, Professor Garvey remarked that it was "comparable with bariatric surgery." However, because paresthesia and hypotension were also observed, he noted that adverse event management would be necessary for real-world clinical use.

Amylin, potential differentiation in both weight loss efficacy and tolerability

At this presentation, Professor Garvey placed particular emphasis on amylin.

Amylin is a hormone cosecreted with insulin from pancreatic beta cells; it acts on regions such as the brainstem and hypothalamus to increase satiety and reduce food intake while delaying gastric emptying.

Preclinical studies have shown that amylin suppresses the decrease in energy expenditure during weight loss and reduces fat mass while potentially preserving muscle mass relatively well. Researchers are also investigating its potential to attenuate bone mass loss.

However, Professor Garvey drew a line by stating that because these effects on muscle and bone are still based on preclinical evidence, further confirmation is required to determine whether they can be replicated in patients.

In clinical settings, a relatively low incidence of gastrointestinal adverse events, along with robust weight loss efficacy, is cited as a major strength.

The long-acting amylin analog petrelintide, under development by Roche and Zealand Pharma, demonstrated a weight reduction exceeding 10% in the Phase 2 ZUPREME-1 trial.

Professor Garvey highlighted that nausea occurred in about 20% of patients, lower than levels typically reported in clinical trials of GLP-1-based agents, and that vomiting, diarrhea, and constipation were also relatively uncommon.

Novo Nordisk's CagriSema, a co-formulation of the amylin analog cagrilintide and semaglutide, demonstrated a weight loss rate of 22.7% at week 68 based on the efficacy estimand in the REDEFINE 1 trial. This exceeded the 16.1% observed with semaglutide monotherapy and 11.8% with cagrilintide monotherapy.

Eli Lilly's investigational selective amylin receptor agonist, eloralintide, also demonstrated weight loss of up to 20.1% based on the efficacy estimand in a 48-week Phase 2 study.

Professor Garvey said long-acting amylin agents show weight-loss efficacy sufficient to anticipate health benefits in short-term clinical trials, while carrying a relatively lower burden of gastrointestinal adverse events. He explained that this underpins the pharmaceutical industry's heightened focus on developing the amylin class.

Drug selection may vary depending on severe obesity and comorbidities

Professor Garvey anticipated that as the pipeline of obesity therapeutics expands, treatment algorithms will be established, much like those for hypertension or diabetes, where agents are tailored to patient conditions and additional medications are introduced as needed.

However, Professor Garvey clarified that this is not currently an established recommendation, but rather a hypothetical treatment strategy grounded in early clinical evidence.

Professor Garvey categorized patients broadly into three types. For patients with a high body mass index (BMI) accompanied by biomechanical complications such as impaired mobility, dual or triple agonists could be considered, as substantial weight reduction of 20% to 25% or more may be required.

For patients with specific comorbidities such as cardiovascular disease or obstructive sleep apnea, Professor Garvey considered administering agents proven effective in improving those complications in clinical trials first.

Conversely, for the broader population of individuals with obesity who do not have specific comorbidities, Professor Garvey mentioned the possibility of utilizing long-acting amylin agonists, which offer sufficient weight loss efficacy along with favorable tolerability, as an initial therapeutic option.

Professor Garvey stated, "In obesity, as in hypertension or diabetes, management can evolve by starting with a well-tolerated drug and then adding other agents if clinical targets are not met," concluding that "as treatment options expand, a more individualized approach will become possible for each patient."