ADA 2026: Obesity Pharmacotherapy and the Future of Weight Management

If there was one therapeutic area that generated excitement throughout the 86th American Diabetes Association (ADA) Scientific Sessions, it was obesity pharmacotherapy. While glucagon-like peptide (GLP)-1 receptor agonists transformed obesity treatment over the past several years, ADA 2026 provided a glimpse into what may come next: triple agonists, amylin analogues, dual GLP-1/glucagon therapies, and next-generation combination approaches capable of producing unprecedented weight loss while improving glycemic control and cardiometabolic health.

The headline story belonged to retatrutide (Eli Lilly). However, the broader message from ADA 2026 was that obesity pharmacotherapy is rapidly evolving beyond GLP-1 monotherapy toward multitarget therapies designed to address obesity as a chronic cardiometabolic disease rather than simply a weight-management condition.

Multiagonist Therapy Is the New Frontier

One of the clearest themes throughout ADA 2026 was that future obesity therapies will likely involve multiple complementary pathways rather than reliance on a single receptor target.

By simultaneously targeting incretin, amylin, and glucagon biology, investigators hope to maximize weight loss while improving glycemic control, satiety, energy expenditure, cardiometabolic risk factors, and potentially organ-specific outcomes such as liver and kidney disease.

CagriSema Advances the Amylin Plus GLP-1 Strategy

Novo Nordisk's investigational fixed-dose combination of semaglutide (Wegovy) and cagrilintide, known as CagriSema, was featured in several presentations.

In a mechanistic study, CagriSema significantly improved appetite control compared with placebo, reducing hunger, lowering energy intake, and improving eating behavior scores. Functional MRI analyses demonstrated treatment-related changes in brain regions involved in satiety, motivation, and food reward, suggesting that CagriSema influences both physiologic and behavioral drivers of eating.¹

Additional data from REDEFINE 1 (NCT05567796) demonstrated significant improvements in craving control, emotional eating, uncontrolled eating, and overall eating behavior compared with placebo. These findings support the complementary biology of combining GLP-1 receptor agonism with amylin receptor agonism.²

Bottom line for pharmacists: CagriSema may provide benefits that extend beyond weight reduction alone by targeting appetite regulation and eating behavior through multiple pathways.

Petrelintide Highlights the Return of Amylin Biology

Another highly anticipated presentation involved petrelintide (Roche), a long-acting amylin analogue evaluated in the phase 2 ZUPREME-1 trial (NCT06662539).

Participants receiving petrelintide achieved placebo-adjusted weight reductions of up to 10.7% while demonstrating improvements in cardiometabolic risk factors. Treatment discontinuation rates were low, and gastrointestinal adverse events (AEs) were generally manageable.³

Petrelintide represents renewed interest in amylin biology as an independent therapeutic pathway and as a potential partner for future combination therapies.

Bottom line for pharmacists: Amylin-based therapies may emerge as important alternatives or complements to traditional GLP-1 receptor agonists.

Zenagamtide (Amycretin) Combines GLP-1 and Amylin in a Single Molecule

Zenagamtide (Novo Nordisk), previously known as amycretin, represents another approach to combining incretin and amylin biology.

In a phase 2b study, once-weekly subcutaneous zenagamtide produced dose-dependent reductions in A_1C and significant reductions in body weight compared with placebo. More participants achieved A_1C targets below 7% and 6.5% compared with placebo. Importantly, no apparent weight-loss plateau was observed at week 36 with higher doses, suggesting the potential for continued weight reduction with longer treatment duration.⁴

Gastrointestinal AEs were consistent with other incretin-based therapies and were generally mild to moderate in severity.⁴

Bottom line for pharmacists: Zenagamtide represents a promising next-generation therapy that integrates GLP-1 and amylin receptor agonism within a single molecule.

Mazdutide Continues to Impress

Among the obesity abstracts presented at ADA 2026, mazdutide (Eli Lilly) generated some of the most impressive data.

In GLORY-2 (NCT06164873), participants achieved a mean weight reduction of approximately 18.5% at 60 weeks, with 44% achieving at least 20% weight loss. Improvements were also observed in blood pressure, lipid parameters, and uric acid levels, while treatment discontinuation rates remained low.⁵

Additional data from DREAMS-3 (NCT06184568) demonstrated superior glycemic and weight outcomes compared with semaglutide 1 mg in adults with type 2 diabetes and obesity.⁶

Supporting mechanistic analyses showed improvements in insulin sensitivity, reductions in Homeostatic Model Assessment for Insulin Resistance, and favorable changes in adiponectin and other metabolic biomarkers.⁷

Exploratory analyses also suggested potential kidney benefits, including improvements in estimated glomerular filtration rate and albuminuria.⁸

Bottom line for pharmacists: Mazdutide may offer benefits extending beyond weight reduction, with potential positive effects on insulin resistance, cardiometabolic risk factors, and kidney health.

Ecnoglutide Demonstrates Head-to-Head Superiority Over Semaglutide

One of the more intriguing late-breaking abstracts evaluated ecnoglutide (Sciwind Biosciences), a novel cAMP-biased GLP-1 receptor agonist, against semaglutide.

At 20 weeks, participants receiving ecnoglutide achieved a mean weight reduction of approximately 12.8% compared with 9.5% for semaglutide (P < .0001). Participants receiving ecnoglutide were also more likely to achieve weight-loss thresholds of at least 5%, 10%, and 15%. Safety and tolerability were comparable between groups, with similar rates of gastrointestinal AEs.⁹

Bottom line for pharmacists: Ecnoglutide may represent a next-generation GLP-1 receptor agonist capable of producing greater weight loss than semaglutide while maintaining a similar safety profile.

What Comes Next?

Perhaps the most fascinating obesity presentations at ADA 2026 focused on what may come after today's dual and triple agonists.

Investigators presented preclinical data on a novel tetra-agonist peptide targeting GLP-1, glucose-dependent insulinotropic polypeptide (GIP), amylin, and calcitonin receptors. In obese animal models, the agent produced greater weight loss, greater fat-mass reduction, and better preservation of lean mass than either tirzepatide (Zepbound; Eli Lilly) or CagriSema.¹⁰

Additional preclinical data highlighted ASC37 (Ascletis Pharma), an investigational oral triple agonist targeting GLP-1, GIP, and glucagon receptors, whereas other investigators presented depot formulations designed to enable once-monthly administration of agents such as tirzepatide and retatrutide.^11,12

These presentations illustrate how rapidly obesity pharmacotherapy continues to evolve.

Retatrutide Steals the Show

Retatrutide, Lilly's investigational triple receptor agonist targeting GLP-1, GIP, and glucagon receptors, emerged as one of the most discussed therapies at ADA 2026. Dedicated symposium sessions highlighted findings from both the TRIUMPH obesity program and the TRANSCEND-T2D-1 trial (NCT06354660) in type 2 diabetes.^13,14

Results presented during the symposium demonstrated weight reductions approaching 30% in obesity trials, placing retatrutide among the most effective pharmacologic weight-loss therapies studied to date. In TRANSCEND-T2D-1, participants achieved A_1C reductions approaching 2%, with up to 85% reaching an A_1C of 6.5% or lower and nearly half achieving an A_1C less than 5.7%. Significant improvements were also observed in body weight, blood pressure, triglycerides, and non–high-density lipoprotein cholesterol.^13,14

Retatrutide remains investigational and is not currently approved for obesity or type 2 diabetes. Nevertheless, the magnitude of both glycemic and weight effects reinforces the growing concept that obesity and type 2 diabetes can be addressed simultaneously through therapies targeting multiple metabolic pathways.

Bottom line for pharmacists: Retatrutide may represent the next major therapeutic advance in obesity and diabetes management, demonstrating the potential of triple agonism to achieve levels of weight loss previously associated only with metabolic surgery.

Survodutide Targets Obesity and Liver Disease Simultaneously

Survodutide (Boehringer Ingelheim), a dual glucagon and GLP-1 receptor agonist, was highlighted during symposium presentations featuring findings from the SYNCHRONIZE clinical program.¹⁵

Presenters reported significant weight loss, reductions in liver fat, and improvements in metabolic dysfunction-associated steatotic liver disease (MASLD). These findings reinforce growing interest in therapies capable of addressing obesity and its complications simultaneously.¹⁵

As obesity increasingly intersects with liver disease, diabetes, and cardiovascular disease, therapies such as survodutide may become important tools for managing multiple obesity-related conditions with a single treatment approach.

Bottom line for pharmacists: Survodutide reflects the growing movement toward therapies designed to address obesity and its comorbidities simultaneously.

What Pharmacists Should Take Away from ADA 2026

Several themes emerged consistently throughout the obesity sessions:

• Retatrutide is currently the most exciting investigational obesity therapy in development.
• Obesity treatment is rapidly moving beyond GLP-1 monotherapy.
• Amylin biology is reemerging as a major therapeutic target.
• Multiagonist therapies are increasingly being designed to improve obesity, diabetes, MASLD, kidney disease, and cardiovascular risk simultaneously.
• The obesity pipeline remains remarkably robust, with multiple agents demonstrating efficacy approaching or exceeding current standards of care.

Looking Ahead

ADA 2026 reinforced that obesity is increasingly being treated as a chronic cardiometabolic disease rather than simply a weight-management issue. The remarkable efficacy demonstrated by investigational therapies such as retatrutide, along with continued advances in amylin analogues, glucagon-based therapies, and multiagonist approaches, suggests that future obesity treatments may achieve even greater improvements in weight, glycemic control, cardiometabolic risk, liver disease, and kidney outcomes.

For pharmacists, understanding this rapidly evolving therapeutic landscape will be essential as obesity pharmacotherapy continues to transform diabetes and cardiometabolic care.

REFERENCES

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2. Dalton M, Becker NP, Bluher M, et al. Effect of CagriSema on eating control and behavior: REDEFINE 1. Diabetes. 2026;75(Suppl 1):1695-P. doi:10.2337/db26-1695-P

3. Garvey WT, Connery L, Dinesen M, et al. Petrelintide, a human amylin analog for the treatment of obesity: efficacy and safety from the phase 2 trial, ZUPREME 1. Diabetes. 2026;75(Suppl 1):3083-LB. doi:10.2337/db26-3083-LB

4. Mora PF, Aroda V, Asong M, et al. Zenagamtide (amycretin), a novel unimolecular GLP-1 and amylin receptor agonist: phase 2b results in type 2 diabetes. Diabetes. 2026;75(Suppl 1):1730-P. doi:10.2337/db26-1730-P

5. Ji L, Gao L, Jiang H, et al. Efficacy and safety of mazdutide 9 mg in Chinese adults with obesity: results from the phase 3 GLORY-2 trial. Diabetes. 2026;75(Suppl 1):1225-OR. doi:10.2337/db26-1225-OR

6. Luo Y, Jiang H, Shi B, et al. Mazdutide vs semaglutide in Chinese adults with type 2 diabetes and obesity (DREAMS-3): a randomized, open-label, phase 3b trial. Diabetes. 2026;75(Suppl 1):1226-OR. doi:10.2337/db26-1226-OR

7. Thomas M, Weideman AMK, Coskun T, et al. Mazdutide improves markers of insulin sensitivity in adults with obesity without type 2 diabetes. Diabetes. 2026;75(Suppl 1):1693-P. doi:10.2337/db26-1693-P

8. Hsia S, Bays HE, Billings LK, et al. Effect of mazdutide on kidney function in adults with obesity or overweight. Diabetes. 2026;75(Suppl 1):1733-P. doi:10.2337/db26-1733-P

9. Ji L, Gao L, Xue H, et al. Efficacy and safety of cAMP-biased ecnoglutide vs unbiased semaglutide in adults with obesity: twenty-week results from a multicenter, randomized, open-label, phase 2 study. Diabetes. 2026;75(Suppl 1):2849-LB. doi:10.2337/db26-2849-LB

10. Ghosh SS, Herrero B, Valdecantos MP, et al. Superior quality of weight loss with a novel unimolecular tetra-agonist peptide targeting GLP-1, GIP, amylin, and calcitonin receptors vs tirzepatide and CagriSema in diet-induced obese rats. Diabetes. 2026;75(Suppl 1):1321-OR. doi:10.2337/db26-1321-OR

11. Wu JJ, Dong K. ASC37 oral tablets, GLP-1R/GIPR/GCGR triple agonist peptide, achieved average absolute oral bioavailability of 4.2% in nonhuman primate studies. Diabetes. 2026;75(Suppl 1):1673-P. doi:10.2337/db26-1673-P

12. Lee J, Seol E, Lee H. A novel, high drug-loading long-acting injectable enables one-monthly subcutaneous administration of tirzepatide and retatrutide. Diabetes. 2026;75(Suppl 1):2815-LB. doi:10.2337/db26-2815-LB

13. Triple hormone therapy demonstrates efficacy for type 2 diabetes and obesity. ADA Meeting News. News release. June 8, 2026. Accessed June 14, 2026. https://www.adameetingnews.org/triple-hormone-therapy-demonstrates-efficacy-for-type-2-diabetes-and-obesity

14. Scientific Sessions 2026 session coverage: obesity and weight management presentations. ADA Meeting News. News release. June 2026. Accessed June 14, 2026.

15. Boehringer Ingelheim. Boehringer Ingelheim’s survodutide Phase III trial showed targeted 34% visceral and 63% liver fat reduction, while minimizing lean mass loss in pre-specified analysis, supporting improved metabolic health in people living with obesity. June 7, 2026. Accessed June 14, 2026. https://www.boehringer-ingelheim.com/us/human-health/metabolic-diseases/positive-data-two-phase-iii-synchronize-obesity-trials