Highlights from ADA 2025: Oral GLP-1s, Amylin combinations, muscle-sparing strategies in obesity treatment, and new frontiers in diabetes care

This week, we attended the American Diabetes Association (ADA) conference, which has firmly established itself as the world’s largest obesity-focused medical meeting. As one of the only investment managers with a conviction-driven thematic strategy targeting this space – the Bellevue Obesity Solutions Fund – we had the opportunity to engage extensively with key opinion leaders, clinical developers, and management teams.

This year’s ADA spotlighted the next generation of obesity and metabolic therapies. While nuanced differences exist across the pipeline, one thing is clear: the space is ripe for further innovation. Oral GLP-1 alternatives, muscle-sparing regimens, and combination hormone therapies all gained traction, pointing toward a maturing market still rich in unmet needs.

In summary, the ADA 2025 highlighted a rapidly evolving field: oral GLP-1s are becoming more competitive, combination therapies are targeting both weight and muscle preservation, China is emerging as a global innovator, and cell-based treatments are inching closer to real-world impact.

The industry is beginning to pivot from «how much weight can we lose» to «how can we lose it better» - with quality of weight loss, patient convenience, and long-term durability now taking center stage. For investors, this evolution opens the door to a second wave of innovation and value creation. As an active manager deeply embedded in the field, we remain committed to identifying and backing the next winners in metabolic health.

Our key takeaways:
A major highlight came from Eli Lilly, which presented full results from ACHIEVE-1, a Phase III trial of Orforglipron, its oral, non-peptide GLP-1 receptor agonist. The once-daily pill showed strong blood sugar and weight reduction in patients with type 2 diabetes, matching oral semaglutide, with no major liver concerns. Some side effects like nausea and constipation persisted, but overall tolerability was considered acceptable.

Novo Nordisk’s CagriSema - a fixed-dose combination of semaglutide and the amylin analogue cagrilintide - also took centre stage. The drug delivered robust weight loss (~23%), but tolerability remains a challenge, with higher rates of nausea, vomiting, and injection site reactions than semaglutide alone. While the combination has been positioned as a potential muscle-sparing therapy, DXA scans showed that about one-third of weight loss still came from lean mass, similar to GLP-1s alone - leaving the clinical benefit of amylin on body composition still unproven.

Amylin gained broader attention at the conference. Novo’s NN1213 and AstraZeneca’s AZD6234 are early-stage amylin candidates that aim to enhance satiety and potentially improve body composition when paired with GLP-1s. Preclinical data from AZD6234 suggested better fat loss with preserved lean mass - a promising direction as combination hormone therapies evolve.

Further emphasizing quality of weight loss, Lilly presented new Phase II results for Bimagrumab (Bima), a myostatin/activin inhibitor. In combination with semaglutide, Bima delivered up to 42.2% fat loss while preserving - or even increasing - lean mass. The highest combo dose achieved 20.2% weight loss, similar to tirzepatide, but with significantly improved body composition. A transient LDL-C rise was observed but is thought to reflect fat mobilization, not safety issues.

Amgen also provided deeper insight into MariTide, its Phase II GLP-1 agonist and GIPR antagonist. New data included breakdowns by dosing frequency and a Phase I titration study that aims to improve tolerability. While efficacy looks solid, investor debate focused on high nausea/vomiting rates, dropouts, and whether dose titration will improve the profile enough to compete.

Internationally, Chinese biotech companies had a strong presence. Ascletis showed some safety and pharmacokinetics for its oral GLP-1 ASC30, structurally similar to Orforglipron. Innovent reported positive Phase III results for Mazdutide, a GLP-1/glucagon dual agonist. Laekna is pursuing therapies aimed at muscle preservation during weight loss - an increasingly important metric in obesity treatment.

Finally, Vertex Pharmaceuticals shared new data from its early-stage cell therapy for type 1 diabetes, which uses lab-grown insulin-producing cells to replace lost pancreatic function. Patients maintained improved blood sugar control for over a year, though immunosuppressants are still required. Vertex is pushing ahead with pivotal trials and developing next-generation, immune-evasive versions.