Editor's Note: The 86th Scientific Sessions of the American Diabetes Association (ADA) is being held in New Orleans, USA. As one of the world's most important academic conferences in diabetes and metabolic diseases, this year's ADA meeting saw multiple biopharmaceutical companies report the latest clinical progress on next-generation glucose-lowering therapies. These developments cover glucagon-like peptide-1 (GLP-1) receptor agonists with less frequent dosing, as well as dual- and triple-mechanism therapies targeting multiple incretin and amylin signaling pathways. The long-acting design, stability optimization, CMC development, and scalable manufacturing capabilities of peptide drugs are becoming critical foundations for advancing next-generation metabolic therapies into the clinic and to patients. WuXi TIDES, a subsidiary of WuXi AppTec, has established an integrated CRDMO platform for peptide drugs, providing synthesis services for all types of peptides, including linear, cyclic, and highly modified peptides, as well as unnatural amino acids, linkers, toxins, and peptide-drug conjugates. The platform supports all stages from drug discovery, CMC development to commercial manufacturing, helping partners more efficiently advance the development of next-generation metabolic disease therapeutics, including GLP-1-related therapies. This article shares with readers several noteworthy clinical advances presented at the ADA Scientific Sessions.
Pfizer reported detailed results from multiple Phase 2b clinical studies of berobenatide at the ADA Scientific Sessions. Berobenatide is an investigational GLP-1 receptor agonist peptide that Pfizer says has the potential for once-monthly dosing. Unlike most current GLP-1 drugs that require weekly administration, a key focus of berobenatide's development is exploring less frequent dosing regimens while maintaining efficacy and tolerability, thereby improving the convenience and adherence of long-term weight management.
In the exploratory extension period of the VESPER-1 study, subjects receiving 2.4 mg once-weekly berobenatide achieved an average weight loss of nearly 16% at Week 32 (unadjusted for placebo), with no plateau observed at that time point. Pfizer stated that data from the VESPER-1, VESPER-2, and VESPER-3 studies support continued development of berobenatide under both weekly and monthly dosing regimens, and demonstrate favorable tolerability in terms of gastrointestinal adverse events and treatment discontinuation. Notably, the VESPER-2 study also showed that in adults with obesity or overweight and concomitant type 2 diabetes, berobenatide (1.6 mg) once weekly achieved a 2.2 percentage-point reduction in glycated hemoglobin (HbA1c) at Week 28, compared with a 0.2 percentage-point reduction in the placebo group.
Based on these results, Pfizer plans to advance a broad late-stage development program for berobenatide in 2026, including ten Phase 3 studies for chronic weight management and obesity-related comorbidities. Relevant indication explorations also include obesity-related diseases such as knee osteoarthritis and obstructive sleep apnea.
Roche's presence in the obesity treatment space also drew attention during the ADA meeting. Data from a Phase 2 clinical trial of Roche's investigational drug enicepatide showed that patients receiving the highest dose achieved an average weight loss of 22.7% at Week 48, with more than one-quarter of subjects in the highest-dose group achieving at least 30% weight loss. Enicepatide is a once-weekly subcutaneously injected investigational GLP-1/glucose-dependent insulinotropic polypeptide (GIP) dual receptor agonist. Its development rationale lies in the synergistic action of multiple metabolic pathways to further enhance therapeutic potential.
This Phase 2 study enrolled 469 adults with overweight or obesity, evaluating the efficacy and safety of enicepatide at multiple dose levels from 4 mg to 24 mg versus placebo. The results showed a clear dose-response relationship, and the weight loss curve had not yet shown a plateau at Week 48. In terms of safety, the rate of discontinuation due to adverse events was 5.9% in the enicepatide group versus 1.3% in the placebo group; most gastrointestinal adverse events were mild to moderate.
Novo Nordisk presented Phase 2 clinical data for its investigational drug zenagamtide at the ADA Scientific Sessions. Zenagamtide, also known as amycretin, is a single-molecule GLP-1 and amylin receptor agonist being developed for the treatment of type 2 diabetes and overweight or obesity in adults. Compared with GLP-1 receptor agonists alone, dual targeting of the GLP-1/amylin signaling pathway is expected to simultaneously affect glycemic control, appetite regulation, and weight management, offering a new combination strategy for metabolic disease treatment.
This Phase 2 dose-finding study evaluated the efficacy and safety of once-weekly subcutaneous zenagamtide in adults with type 2 diabetes. Enrolled patients had inadequate glycemic control, with baseline HbA1c of 7.0% to 10.0%, were receiving stable doses of metformin, and some were also using SGLT2 inhibitors. The results showed that at Week 36, all zenagamtide dose groups achieved statistically significant HbA1c reductions compared with placebo. The highest dose group (40 mg) achieved an estimated mean HbA1c reduction of up to 1.71 percentage points, with up to 89.1% of subjects achieving the treatment goal of HbA1c below 7%, and up to 76.2% achieving HbA1c ≤6.5%.
In terms of weight management, zenagamtide also demonstrated significant effects. At Week 36, subjects receiving the 40 mg dose achieved a mean weight loss of 14.6%, compared with 2.1% in the placebo group. In the higher-dose groups, investigators had not yet observed a clear weight loss plateau. In terms of safety, the most common adverse events were gastrointestinal reactions, and most were mild to moderate. Based on these results, Novo Nordisk plans to initiate a Phase 3 clinical development program for zenagamtide in adults with type 2 diabetes in the second half of 2026.
Eli Lilly and Company presented additional positive results from the pivotal Phase 3 clinical trials of retatrutide at the ADA Scientific Sessions. Retatrutide is a potential first-in-class investigational GIP, GLP-1, and glucagon triple hormone receptor agonist. Trial results showed that retatrutide produced significant weight loss while also delivering clinically meaningful improvements in common obesity-related conditions such as knee osteoarthritis pain, moderate-to-severe obstructive sleep apnea, and type 2 diabetes. Results from the TRIUMPH-1 and TRANSCEND-T2D-1 studies were presented at the ADA Scientific Sessions, with TRANSCEND-T2D-1 results published simultaneously in The Lancet .
TRIUMPH-1 included a clinical trial in adults with obesity, along with two nested basket trials: one for knee osteoarthritis pain and another for moderate-to-severe obstructive sleep apnea. At Week 80, retatrutide met the primary endpoint in each trial, delivering potent weight loss while significantly improving knee osteoarthritis pain and obstructive sleep apnea. Subjects receiving retatrutide at 9 mg and 12 mg achieved mean weight losses of 64.4 pounds (25.9%) and 70.3 pounds (28.3%), respectively. Notably, among subjects treated with retatrutide (12 mg), 65.3% achieved a body mass index (BMI) below 30, and 33.3% reached a BMI below 25, the healthy BMI range. In a prespecified extension study in subjects with baseline BMI ≥35, subjects who continued retatrutide (12 mg) treatment up to 104 weeks achieved a mean weight loss of 85.0 pounds (30.3%).
In addition to improving weight metrics, in subjects with knee osteoarthritis, retatrutide reduced WOMAC pain subscale scores from a baseline of 6.0 by up to 4.3 points (73.1%); in subjects with moderate-to-severe obstructive sleep apnea, retatrutide reduced the apnea-hypopnea index (AHI) from a baseline of 58.6 events per hour by up to 36.1 events per hour (60.6%).
It is worth noting that the multiple investigational therapies that received widespread attention at this year's ADA Scientific Sessions-including berobenatide, enicepatide, petrelintide, zenagamtide, and retatrutide-are all peptide drugs or innovations based on peptide design. At the same time, the combined targeting strategy of multiple metabolic regulatory pathways such as GLP-1, GIP, amylin, and glucagon is also driving peptide drug design toward more complex molecular structures and longer-acting dosing modalities. As an increasing number of next-generation metabolic therapies advance into late-stage clinical development, integrated platforms capable of unifying discovery, development, and manufacturing capabilities are becoming critical enablers for the efficient translation of innovative outcomes. As an enabler of pharmaceutical innovation, WuXi AppTec has leveraged synergies across its multi-business platforms to build a peptide drug R&D system covering drug discovery, mechanism research, pharmacokinetic evaluation, and development and manufacturing, providing end-to-end support for partners.
WuXi AppTec's Biology business platform (WuXi Biology) has built an integrated solution covering early peptide discovery and optimization, providing systematic support from lead compound discovery to candidate molecule advancement. The platform integrates complementary discovery technologies such as peptide DNA-encoded compound libraries (DEL) and display technologies (phage display and mRNA display), exploring over trillions of molecular diversity spaces within a single project to achieve efficient peptide lead compound discovery. Relying on a ready-made peptide library of over 300 billion molecules and highly customizable design capabilities, the platform supports the construction of linear peptides and cyclic peptides, and can introduce thousands of unnatural amino acids and multiple cyclization strategies to enhance molecular stability and druggability potential. During the "Hit-to-Lead" optimization phase, WuXi Biology combines high-throughput decoding, computational modeling, and machine learning, and systematically characterizes binding, permeability, stability, and function through biophysical, biochemical, structural biology, cellular, and DMPK assessment systems, accelerating structure-activity relationship (SAR) iteration and peptide performance optimization. By deeply connecting discovery technologies, functional biology, and downstream development capabilities, WuXi Biology helps clients reduce early R&D risks and accelerate the transformation of peptide innovations into clinical candidate drugs.
WuXi AppTec's Bioanalytical Services (BAS) leverages a highly mature bioanalytical technology platform to build a systematic analytical solution oriented toward the development needs of next-generation peptide drugs, effectively addressing the complex challenges of pharmacokinetic and immunogenicity studies for peptide molecules in clinical trials. As peptide drug molecular weights increase, structural modifications multiply, and conjugation forms become increasingly complex, their bioanalysis faces a series of unique challenges: on one hand, peptides typically exhibit multiple charge-state distributions and non-uniform ionization efficiency in liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, leading to signal dispersion and ion suppression, thereby affecting detection sensitivity and method robustness; on the other hand, peptides have limited epitopes and are highly homologous to endogenous peptide sequences, often exhibiting low immunogenicity and making specific antibody preparation difficult, while ligand-binding assays (LBA) are prone to endogenous interference and cross-reactivity, increasing the complexity of immunogenicity evaluation. In addition, structural modifications such as fatty acid conjugation, PEGylation, or protein fusion that extend half-life may also introduce new immunogenicity risks (such as anti-PEG antibodies), imposing higher requirements on anti-drug antibody and neutralizing antibody (NAb) detection.
Addressing these industry pain points, WuXi AppTec's Bioanalytical Services integrates high-sensitivity LC-MS/MS, immuno-capture mass spectrometry, ELISA/MSD platforms, and cell-based functional analysis methods to achieve integrated support for PK analysis, anti-drug antibody, and neutralizing antibody (NAb) evaluation. By optimizing sample pre-processing strategies, establishing immuno-capture mass spectrometry coupling techniques, and bottom-up analysis methods based on trypsin digestion, detection sensitivity can be significantly improved and matrix interference reduced, demonstrating good method specificity and robustness in the analysis of complex modified peptides and long-chain peptides. At the same time, addressing the detection difficulties caused by low immunogenicity and high homology in peptide drug immunogenicity evaluation, the team has established a tiered immunogenicity evaluation system, integrating bridging anti-drug antibody detection, confirmatory assays, and titer analysis, and combining strategies such as acid dissociation (ACE) and minimum required dilution (MRD) optimization to improve drug tolerance and detection sensitivity; by optimizing labeled reagent design and methodological conditions, endogenous interference and non-specific binding are effectively reduced, and combined with cell-based functional NAb analysis methods, full-process coverage from anti-drug antibody screening to neutralizing effect evaluation is achieved, thereby systematically supporting immunogenicity risk assessment for complex modified peptides and conjugated peptide drugs.
WuXi AppTec's bioanalytical technology platform has successfully supported clinical PK studies and immunogenicity assessments for next-generation peptide drugs such as GLP-1 analogs and insulin analogs, forming end-to-end capabilities covering method development, validation, and sample testing. Relying on standardized processes and multi-technology synergy advantages, WuXi AppTec's Bioanalytical Services can provide partners with high-sensitivity, high-reliability bioanalytical support for peptide drugs, accelerating the advancement of innovative peptide therapies from the research stage to clinical development.