Can dual agonist drugs like amycretin and tirzepatide replace bariatric surgery by 2030?

As Novo Nordisk A/S (CPH: NOVO-B) and Eli Lilly and Company (NYSE: LLY) race to redefine obesity care, a pivotal question is emerging: could advanced pharmacological agents such as amycretin and tirzepatide rival, or even replace, bariatric surgery by the end of this decade? With dual agonist drugs delivering weight loss outcomes nearing surgical benchmarks in controlled trials, healthcare professionals, investors, and payers alike are re-evaluating the future of chronic weight management.

Historically, bariatric surgery has been the most effective intervention for sustained weight loss in people with severe obesity, with procedures like gastric bypass and sleeve gastrectomy leading to average reductions of 25–30 percent within a year. However, with Novo Nordisk’s amycretin reporting up to 24.3 percent weight loss in phase 2 data and Eli Lilly’s tirzepatide achieving up to 22.5 percent reductions in trials, the treatment gap may be narrowing faster than expected.

How do dual agonist drugs compare to bariatric surgery in terms of weight loss efficacy and clinical durability?

Amycretin, a once-weekly dual GLP-1 and amylin receptor agonist in development by Novo Nordisk, delivered a 24.3 percent mean weight reduction over 36 weeks at its highest tested subcutaneous dose in early-stage clinical trials. Tirzepatide, Eli Lilly’s approved dual GLP-1 and GIP receptor agonist marketed as Zepbound in obesity, demonstrated average weight loss ranging from 15 to 22.5 percent in the SURMOUNT-1 and SURMOUNT-2 trials over 72 weeks.

By comparison, sleeve gastrectomy and Roux-en-Y gastric bypass typically deliver 25–30 percent weight loss after 12 months and maintain over 20 percent loss for up to 10 years in longitudinal studies. However, a real-world analysis published in June 2025 involving over 38,500 patients found that while bariatric surgery led to a sustained 24 percent weight reduction, patients using GLP-1 drugs like semaglutide and tirzepatide only maintained about 5–7 percent weight loss over the same period due to adherence issues and discontinuation rates.

These findings suggest that while pharmacologic agents are achieving surgical-level results in trials, real-world durability remains a hurdle. Nonetheless, if newer agents like amycretin and advanced oral formulations of GLP-1 agonists can improve adherence and long-term outcomes, they may begin to encroach upon the surgical standard.

What are the metabolic benefits of dual agonist drugs compared to surgery beyond weight loss?

Bariatric surgery has long been associated with systemic metabolic improvements beyond weight loss, including type 2 diabetes remission, reduced cardiovascular risk, and lower incidence of obesity-related cancers. Studies have shown that up to 80 percent of patients undergoing gastric bypass experience remission of type 2 diabetes, while cardiovascular mortality risk can decline by more than 40 percent within a decade.

Tirzepatide has also demonstrated cardiovascular benefits, including a 38 percent reduction in heart failure hospitalizations and improved glycemic control. Novo Nordisk’s amycretin, which combines GLP-1 and amylin pathways in a single molecule, is believed to enhance satiety and glucose regulation synergistically, although long-term cardiovascular outcome data are not yet available. Both companies are preparing for or initiating large cardiovascular outcome trials (CVOTs) to strengthen the real-world value proposition of their therapies.

Until such trials are complete, surgery retains an edge in demonstrating durable systemic metabolic impact. But pharmacological agents may eventually compete across a broader clinical profile if efficacy extends beyond appetite regulation to risk modification.

What role does patient adherence play in determining the long-term success of obesity pharmacotherapy?

Adherence and tolerability are emerging as major differentiators between pharmacologic and surgical approaches. Real-world evidence suggests that over 60 percent of patients discontinue GLP-1 receptor agonist therapy within 12 months, citing gastrointestinal side effects, cost, or insurance coverage limits. Novo Nordisk’s Wegovy and Ozempic and Eli Lilly’s Zepbound and Mounjaro all carry similar risk profiles, with nausea and vomiting being the most common adverse events.

Amycretin has shown a tolerability profile consistent with other GLP-1 and amylin receptor agonists, with most adverse events rated as mild to moderate and resolving over time. Oral semaglutide and oral amycretin, which are now in development, may help address adherence issues by eliminating the injection barrier, thereby increasing long-term treatment compliance.

In contrast, bariatric surgery, while invasive and associated with perioperative risk, typically results in a one-time intervention with limited need for ongoing adherence to pharmacotherapy—though nutritional supplementation and follow-up remain necessary.

What are the cost implications of dual agonist drugs versus surgical interventions in obesity care?

Cost-effectiveness is a major concern for payers and policymakers. Bariatric surgery, while expensive upfront (US$15,000–30,000), is a one-time cost that may be offset by long-term reductions in obesity-related healthcare expenditures. In contrast, GLP-1-based pharmacotherapy costs between US$900 and US$1,400 per month in the U.S. and requires ongoing administration to maintain results.

Analysts have noted that the lifetime cost of obesity drugs could surpass the one-time surgical investment within 2–3 years, especially in the absence of value-based contracting or biosimilar competition. This economic reality poses a significant barrier to broad insurance coverage for obesity drugs—particularly among public payers like Medicare and Medicaid.

To address this, Novo Nordisk and Eli Lilly are increasingly engaging in pricing negotiations, formulary access programs, and patient assistance models. Future drug pricing and access strategies could determine whether these therapies become accessible alternatives or remain restricted to niche segments.

What is the outlook for dual agonist drugs as potential replacements or complements to bariatric surgery by 2030?

Institutional investors are cautiously optimistic about the potential for dual agonist drugs to disrupt the surgical obesity treatment paradigm. Following amycretin’s phase 1b/2a data release and Novo Nordisk’s announcement to move into phase 3 trials by early 2026, sentiment has improved after a volatile quarter driven by mixed results from other pipeline candidates like CagriSema.

Tirzepatide’s market traction in both diabetes and obesity continues to grow, with Zepbound generating nearly US$2 billion in sales in the first half of 2025. Novo Nordisk’s revenue from GLP-1 franchise drugs remains strong, but investors are watching closely to see whether amycretin can achieve a differentiated profile and secure reimbursement at competitive levels.

Experts believe that if amycretin delivers consistent real-world efficacy above 20 percent weight loss, oral formats reduce discontinuation, and long-term outcomes rival surgery, then pharmacologic treatments could become viable first-line options for moderate to severe obesity. However, surgery will likely remain essential for patients with extreme BMI levels, rapid comorbidity progression, or drug intolerance.

What will determine whether pharmacologic therapies can fully replace bariatric surgery in the next five years?

Whether dual agonist drugs can replace bariatric surgery will depend on several converging factors. First, long-term clinical durability and cardiovascular safety must be proven through extended real-world trials and CVOTs. Second, delivery innovations—especially oral and small-molecule formats—must improve adherence and reduce side effects. Third, pricing models must evolve to ensure sustainable access, particularly for public health systems and uninsured populations.

Finally, patient preference will play a decisive role. A significant subset of patients remains reluctant to undergo surgery due to fear, stigma, or post-operative dietary restrictions. If drugs can deliver near-equivalent results without surgical risk, their appeal could rise substantially.

While dual agonist therapies may not fully displace bariatric surgery by 2030, they are likely to redefine the standard of care for millions of patients with obesity. The next five years will determine whether these pharmacologic innovations become alternatives or just adjuncts to surgical intervention.