The Next Chapter Of Obesity And Type 2 Diabetes Care: ADA 2026 Signals A More Personalized Future

By Karen Zhu, Ph.D., business analyst; Austin Jeffries, Ph.D., consultant; and Erin Law, MS, consultant, Lifescience Dynamics

For more than 15 years, Novo Nordisk and Eli Lilly have shaped the obesity and type 2 diabetes (T2D) treatment landscape through successive waves of GLP-1 innovation. The market has progressed from first-generation agents, such as liraglutide and dulaglutide, to the blockbuster successors, semaglutide and tirzepatide, and more recently to the emergence of oral therapies, including oral semaglutide (approved December 2025) and orforglipron (approved April 2026). Against this backdrop, the American Diabetes Association 2026 conference shined a spotlight on the next wave of innovation in obesity and T2D care, as established leaders and emerging competitors presented pivotal registrational data for next-generation candidates expected to enter the market over the coming years.

At the European Congress on Obesity (ECO) 2026, Lilly presented the first data on treatment deescalation approaches to maintain patients on therapy as the chronicity of obesity is increasingly recognized. Treatment goals are evolving beyond efficacy alone and now also emphasize long-term adherence and overall improvements to health. In response, companies are pursuing differentiated strategies to address diverse patient needs and preferences, positioning themselves within an increasingly competitive market. Dosing and tolerability profiles, given their impact on adherence, are becoming important differentiators in messaging. Additionally, given the persistent presence of non-responders across clinical trials and the lack of predictive tools to identify them, efforts to develop novel non-incretin therapies, including amylin-targeting therapies, are accelerating.

Continued Exploration Of Oral Options

Oral therapies may appeal to patients seeking a convenient daily pill alternative to the weekly injectable treatments that currently dominate the obesity market, potentially improving accessibility and treatment uptake.

Data from the Phase 3 ACHIEVE program, presented at ADA 2026 (CT-SY19-1.5; 1253-OR; 1254-OR; 1715-P), demonstrated superior glycemic control of orforglipron in T2D compared with placebo and active comparators, including SGLT2 inhibitors and semaglutide (A1C reduction with orforglipron vs. dapagliflozin: 1.7% vs. 0.8%; vs. semaglutide 2.2% vs. 1.4%). These data are expected to support the ongoing regulatory review of orforglipron for T2D in the EU (following filing in January 2026) and anticipated U.S. submission.

Beyond this, a growing pipeline of oral GLP-1 therapies is advancing through clinical development, with several competitors also presenting data at ADA 2026. Notable examples included ribupatide (Hengrui/Kailera; 2816-LB), elecoglipron (AstraZeneca; CT-SY22-1; 2844-LB), aleniglipron (Structure Therapeutics; 3101-LB; 3061-LB), and ASC30 (Ascletis; 1672-P), highlighting the next wave of entrants poised to intensify competition in the oral obesity and T2D treatment landscapes.

Long-Acting GLP-1s: Less Frequent Dosing

While oral therapies may appeal to patients who prefer pills over injections, the requirement for daily administration may not align with all patient lifestyles. An alternative strategy is to reduce dosing frequency through longer acting injectable therapies. This approach has been pursued by Pfizer, with the company presenting Phase 2b data from the VESPER program evaluating berobenatide for the treatment of obesity (CT-SY25-1.5). Berobenatide is being developed as an ultra-long-acting GLP-1 receptor agonist with the potential for once-monthly maintenance dosing, compared with the current standard of once-weekly administration. Based on efficacy data (12.3% placebo-adjusted weight loss at week 28 with the medium [4.8 mg] monthly maintenance dosing regimen), berobenatide may offer an effective alternative to both daily oral and weekly injectable treatments and could support long-term adherence.

Holistic Health Benefits Of Dual Agonists And Alternative Mechanisms Of Action

While GLP-1 receptor agonists have defined the modern therapeutic landscape for the treatment of obesity, interest is increasingly shifting toward combination approaches that build on the established GLP-1 paradigm. Presentations at ADA 2026 highlighted two prominent strategies: GLP-1/glucagon (GCG) dual agonism and GLP-1/amylin-based therapies.

The addition of glucagon receptor agonism to GLP-1 is believed to provide broader metabolic benefits, particularly in the liver, making this approach attractive for the treatment of obesity-related comorbidities, such as metabolic dysfunction-associated steatohepatitis (MASH). Data presented for survodutide (Boehringer Ingelheim; CT-SY16-1.5) and mazdutide (Innovent and Eli Lilly; 1225-OR; 1226-OR; 1693-P; 1733-P; 2505-P) reinforced this rationale, with both agents demonstrating liver health benefits, including reductions in liver fat compared with placebo (survodutide demonstrated a relative reduction in liver fat of >30% in 84.2% patients vs. 24.3% for placebo).

Novo Nordisk has focused on combining GLP-1 and amylin biology. ADA 2026 featured data from two such assets: CagriSema (CT-SY-18-1.5; 1035-OR; 1695-P), a fixed-dose combination of cagrilintide (amylin) and semaglutide (GLP-1), and zenagamtide (1323-OR; 1730-P), a single-molecule GLP-1/amylin dual agonist. In trials involving patients with T2D, these therapies demonstrated improvements in glycemic control beyond those achieved with GLP-1 monotherapy or placebo (A1C reductions of 1.8% for CagriSema and 1.71% for zenagamtide vs. placebo values of 0.2% and 0.14%, respectively), which may further support the potential of amylin-based combination strategies.

Triple Agonists: Efficacy Is King?

For patients prioritizing maximal weight loss, triple agonists may represent the next frontier in treatment of obesity. ADA 2026 featured data from leading candidates from Novo Nordisk’s and Eli Lilly’s portfolios, demonstrating substantial efficacy in both weight reduction and obesity-related comorbidities.

Phase 3 data for Lilly’s retatrutide showed up to 28.3% weight loss in individuals without T2D and up to 16.8% in those with T2D, exceeding the efficacy of currently available therapies (CT-SY17-1.5). Similarly, Phase 2 data for UBT251, The United Laboratories’ triple agonist licensed to Novo Nordisk (3090-LB), demonstrated a mean weight-loss efficacy of 16.9%, higher than semaglutide at the same stage of development (13.8%).

However, these efficacy gains come at the cost of reduced tolerability, with higher rates of adverse events (89.2%), particularly vomiting (25.3%) and nausea (42.4%), and treatment discontinuation (10.5%) compared to mono- and dual-agonist therapies. As such, triple agonists may be best suited to patients willing to trade tolerability for maximal efficacy.

Lessons For Discovery And Early Development

As the pipeline of therapies targeting obesity continues to expand, future success will hinge on addressing underserved niche populations. For example, despite the high efficacy of incretin therapies (GLP-1/GIP/GCG-targeting), trials to date point to a small percentage of non-responders that may even gain weight on treatment. These patients likely require non-incretin-based approaches to weight loss, though limited novel mechanisms are being evaluated to date.

Late-stage trials may also pose a challenge for early-stage development, as regulatory expectations for pivotal trial design are likely to shift with increasing access to therapy. Retaining patients in the placebo arm of pivotal studies has become increasingly challenging, with many physicians speculating future studies will require the use of an active comparator. This suggests next-generation therapies may face a higher bar to regulatory approval, reinforcing a likely need to demonstrate differentiation in niche populations.

Diverse Options For The Future

As these products launch over the coming years, patients and healthcare providers will have access to a broader range of treatment options, enabling decisions that reflect individual goals, preferences, and lifestyles rather than being driven solely by weight loss efficacy.

Insights from ADA 2026 suggest that healthcare is evolving toward a more holistic treatment paradigm, with increasing emphasis on overall health outcomes, including the management of comorbidities, cardiovascular and liver health, as well as factors such as dosing convenience, tolerability, and safety. However, despite this shift in clinical priorities, investors and analysts continue to view efficacy as the primary driver of market growth, creating a potential divergence between what healthcare providers value and what the market rewards. This disconnect may force companies to balance competing expectations as they shape future development and commercialization strategies.

About The Authors

Karen Zhu, PhD, is a business analyst at Lifescience Dynamics with expertise in chemical biology, supporting clients across a range of projects including cardiometabolic indications.

Austin Jeffries, PhD, is a consultant at Lifescience Dynamics with five years of experience managing and executing projects in support of clients across cardiovascular, renal, and metabolic diseases.

Erin Law, MSc, is a consultant at Lifescience Dynamics in London with several years of experience in biopharma consulting. She has developed expertise in immunology, neurology, and women’s health through supporting various clients in competitive intelligence projects.