From June 20 to 23, 2025, the 85th Scientific Sessions of the American Diabetes Association (ADA) convened in Chicago, USA. As the world’s largest and most influential conference in the field of diabetes and metabolic diseases, the event brought together leading pharmaceutical companies and research institutions to showcase the latest clinical progress in innovative metabolic therapies.

Wegovy + Bimagrumab: A Dual Breakthrough in Fat Loss and Muscle Preservation

At the ADA meeting, Eli Lilly and Novo Nordisk unveiled new data from the Phase 2b BELIEVE trial, evaluating the combination of Wegovy (semaglutide) with Bimagrumab for the treatment of obesity. Bimagrumab is a first-in-class monoclonal antibody that targets activin type II receptors (ActRII), promoting muscle preservation and growth.

Results from the BELIEVE trial showed that after 72 weeks, participants receiving the combination therapy experienced an average weight reduction of 22.1%, significantly outperforming Bimagrumab alone (10.8%) and semaglutide alone (15.7%). Notably, 92.8% of the weight lost was attributed to fat mass, far exceeding the 71.8% observed with semaglutide monotherapy. Additionally, the combo therapy led to greater reductions in abdominal fat and inflammation-related biomarkers, highlighting its potential as a more sustainable and health-optimized obesity treatment strategy. [1]

Orforglipron: A Milestone in Oral GLP-1 RA Development

Eli Lilly also presented positive topline Phase 3 results from ACHIEVE-1, evaluating the safety and efficacy of orforglipron compared to placebo in adults with type 2 diabetes and inadequate glycemic control with diet and exercise alone. Orforglipron is the first small-molecule GLP-1 receptor agonist, taken without food and water restrictions, to successfully complete a Phase 3 trial.

At 40 weeks, all three doses (3 mg, 12 mg, 36 mg) of orforglipron achieved the primary endpoint of superior A1C reduction compared to placebo, lowering A1C by 1.3% to 1.6% from a baseline of 8.0%, with improvements seen as early as 4 weeks.

Figure 1. Efficacy Estimand Change from Baseline HbA1c, source: https://investor.lilly.com/static-files/36604492-7d65-4649-bc20-f7b4372c2b2b 

Additionally, the 12 mg and 36 mg doses demonstrated clinically meaningful and statistically significant reductions in body weight compared to the placebo. Participants taking the highest dose of orforglipron (36 mg) experienced a mean weight loss of 7.3 kg, or 7.9%, compared with 1.3 kg or 1.6% in the placebo group. [2]

The safety profile of Orforglipron was consistent with existing GLP-1 therapies, with the most common adverse events being mild to moderate gastrointestinal symptoms such as diarrhea, nausea, dyspepsia, and constipation. By overcoming the low oral bioavailability challenges of peptide GLP-1 RAs, Orforglipron represents a disruptive innovation that could reshape the treatment paradigm for type 2 diabetes.

CagriSema: A Dual-Target Therapy for Obesity and Type 2 Diabetes

Novo Nordisk unveiled the Phase 3 results from the REDEFINE 1 and REDEFINE 2 studies of CagriSema, a fixed-dose combination of cagrilintide (an amylin analog) and semaglutide. Designed to reduce appetite, decrease energy intake, and increase satiety, CagriSema has shown promising results in both weight management and type 2 diabetes.

• • In REDEFINE 1, which enrolled 3,400 adults without diabetes but with at least one weight-related condition, CagriSema led to an average weight loss of 20.4% at Week 68, compared to 14.9% with semaglutide, 11.5% with cagrilintide, and 3% with placebo. Among participants with full adherence, the weight loss reached 22.7%, with 40.4% losing more than 25% of their body weight and over 50% reducing their BMI below the obesity threshold.
• •In REDEFINE 2, which included 1,200 people with type 2 diabetes, the CagriSema group achieved a 13.7% average weight reduction (vs. 3.4% with placebo), rising to 15.7% with full adherence. Impressively, 83.6% lost more than 5%, and 22.9% lost more than 20% of their body weight. [3]

Next-Generation Dual and Multi-Targeted Therapies on the Rise

Amycretin: A Promising Dual GLP-1/Amylin Receptor Agonist

Also making headlines at ADA 2025 was Amycretin (NNC0487-0111), a novel, unimolecular GLP-1 and amylin receptor agonist under development by Novo Nordisk. By engaging two complementary pathways involved in appetite regulation and satiety, Amycretin is designed to offer superior weight loss outcomes.

In a 36-week Phase 1b/2a trial, participants receiving 60mg weekly of Amycretin reported body weight reductions of up to 24.3% versus 1.1% with placebo after 36 weeks of treatment.

Eloralintide (LY3841136): A Selective Amylin Receptor Agonist

Eli Lilly also shared Phase 1 data on Eloralintide (LY3841136), a selective amylin receptor agonist that mimics the natural hormone amylin to regulate appetite and blood glucose.

In a 12-week trial involving individuals with a BMI of 27–43 kg/m², the highest-dose group achieved an 11.3% average weight reduction, a top-tier result for early-stage trials. Eloralintide was well tolerated, with a low incidence of gastrointestinal side effects. The most commonly reported events were decreased appetite (19%), headache (12%), fatigue (11%), and COVID-19 infection (11%), most of which were mild.

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Figure 2. Eloralintide: Efficacy at 12 Weeks, source: https://investor.lilly.com/static-files/36604492-7d65-4649-bc20-f7b4372c2b2b 

Notably, Eli Lilly has initiated a Phase 2 trial evaluating Eloralintide in combination with tirzepatide, aiming to explore a multi-targeted approach to weight management.

Looking Ahead: The Future of Metabolic Therapies

The 2025 ADA Scientific Sessions reaffirmed the transformative potential of GLP-1–based innovations in managing metabolic diseases. From combination therapies that preserve muscle mass, to oral agents breaking bioavailability barriers, and dual-agonists redefining treatment strategies—each advancement marks a critical step forward for the millions living with obesity and type 2 diabetes.

With numerous promising therapies advancing through clinical pipelines and poised for regulatory review, the field is entering a new era of effective, convenient, and personalized metabolic care. The future looks brighter than ever for patients, and the science driving it.
 

References:
[1] https://diabetes.org/newsroom/press-releases/new-glp-1-therapies-enhance-quality-weight-loss-improving-muscle-0
[2] https://investor.lilly.com/news-releases/news-release-details/lillys-oral-glp-1-orforglipron-showed-compelling-efficacy-and
[3] https://diabetes.org/newsroom/press-releases/cagrisema-demonstrates-significant-weight-loss-adults-obesity
[4] https://www.prnewswire.com/news-releases/novo-nordisk-advances-early-stage-obesity-medication-amycretin-to-phase-3-clinical-development-based-on-early-phase-clinical-trial-results-in-people-with-obesity-or-excess-weight-published-in-the-lancet-302487500.html
[5] https://theaarterychronicles.com/blogs/eli-lillys-new-obesity-drug-shows-11-weight-loss/