How oral obesity drugs are changing treatment access: A look at semaglutide, amycretin, and orforglipron

Novo Nordisk A/S (CPH: NOVO-B) and Eli Lilly and Company (NYSE: LLY) are accelerating the next wave of obesity pharmacotherapy through the development of oral GLP-1 receptor agonists. With oral amycretin and high-dose oral semaglutide gaining momentum at Novo Nordisk, and Eli Lilly’s non-peptide candidate orforglipron advancing through phase 3, the transition from injectables to pills is emerging as a strategic inflection point in global obesity care. These oral agents promise to lower barriers to treatment, expand access to underserved populations, and ease payer concerns related to delivery logistics and long-term adherence.

Historically, GLP-1 drugs such as semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) have achieved double-digit weight loss through subcutaneous administration. However, many patients avoid injections due to discomfort, storage requirements, or cultural hesitancy, limiting uptake despite widespread obesity prevalence. The industry’s pivot toward oral formats aims to address these limitations while preserving efficacy.

How do oral GLP-1 obesity drugs compare to injectables in terms of weight loss and patient outcomes?

Novo Nordisk reported that participants treated with oral amycretin achieved a mean body weight reduction of 13.1 percent over 12 weeks in early-phase trials. The investigational agent, which targets both GLP-1 and amylin receptors, is also being evaluated in an injectable form that reached 24.3 percent weight loss over 36 weeks. The oral version showed no signs of plateauing during the trial period and was well tolerated, with most adverse events being mild to moderate gastrointestinal symptoms.

In parallel, oral semaglutide has demonstrated a weight loss of 16.6 percent over 64 weeks in the phase 3 OASIS 1 trial, significantly outperforming placebo. Novo Nordisk has submitted oral semaglutide for regulatory review in the obesity indication, building on its prior approval for type 2 diabetes.

Eli Lilly’s orforglipron, a once-daily, non-peptide small molecule GLP-1 receptor agonist, is being developed for both obesity and type 2 diabetes. In the phase 3 ACHIEVE-1 study, patients treated with orforglipron achieved up to 7.9 percent weight loss and HbA1c reductions of up to 1.6 percentage points over 40 weeks. Although the weight loss outcomes are not as high as those seen with injectable semaglutide or tirzepatide, orforglipron’s pill format offers greater convenience and could significantly improve access.

What are the clinical differences between oral semaglutide, oral amycretin, and orforglipron in obesity therapy?

Each oral agent brings distinct biological and formulation characteristics to the market. Oral semaglutide is a peptide-based GLP-1 receptor agonist formulated with an absorption enhancer to facilitate gastrointestinal uptake. It requires administration under fasting conditions with strict timing, which may limit adherence.

Amycretin, also peptide-based, targets two hormone receptors—GLP-1 and amylin—offering dual action on appetite and satiety. Its oral formulation is designed for daily use and, according to early trial data, does not show significant tolerability issues. Novo Nordisk plans to launch phase 3 trials of both the oral and subcutaneous versions by early 2026.

Eli Lilly’s orforglipron is the first non-peptide GLP-1 agonist to reach late-stage development. Its small molecule design allows for easier manufacturing, room-temperature stability, and potentially lower production costs. Unlike oral semaglutide, orforglipron does not require fasting or timing constraints, which may improve adherence and expand its use in general practice settings.

Why are pharmaceutical companies focusing on oral GLP-1 drugs to expand obesity treatment access?

The shift to oral formats reflects a broader strategy to democratize access to obesity treatment. In many markets, needle-based therapy remains stigmatized, impractical, or inaccessible due to cold-chain and training requirements. Oral drugs eliminate the injection barrier and allow primary care physicians to initiate therapy without specialist intervention.

Oral agents are also more attractive to patients with moderate obesity who may not qualify for bariatric surgery or are hesitant to commit to injectable regimens. Analysts note that oral GLP-1 drugs could significantly increase the addressable market by reaching earlier-stage patients and those with mild metabolic dysfunction.

Pharmaceutical companies also see oral drugs as a key avenue for penetrating emerging markets where healthcare infrastructure limits injectable adoption. Orforglipron’s non-peptide formulation, in particular, could unlock access in geographies with constrained refrigeration or high transportation costs.

What are the economic and payer implications of shifting from injectable to oral obesity drugs?

Cost and insurance access remain central challenges in the obesity drug space. Injectable GLP-1 drugs are priced between US$900 and US$1,400 per month, prompting many payers to impose step therapy or require prior authorization. Long-term adherence is also an issue, with real-world studies showing discontinuation rates of 50–70 percent within the first year.

Oral formulations could help address these concerns. Eli Lilly has indicated that orforglipron will be priced lower than injectables, citing its small molecule nature and simplified manufacturing. Novo Nordisk has yet to disclose pricing for oral amycretin, but the company has signaled interest in volume-based models and price-tiered strategies to ensure broader access.

Payers are watching trial data closely to evaluate the long-term efficacy and durability of weight loss from oral agents. Real-world effectiveness, cardiovascular risk reduction, and improvements in comorbid conditions will determine whether insurers adopt these drugs into formularies for chronic obesity care.

How are analysts and institutional investors evaluating the future of oral obesity therapeutics?

The investment community sees oral GLP-1 drugs as a high-growth subsegment within the broader obesity pharmacotherapy market, which could exceed US$100 billion globally by 2030. Eli Lilly’s stock rose 13 percent on June 10, 2025, after it reported positive data from the ACHIEVE-1 trial for orforglipron—the company’s largest single-day gain in over two decades. Analysts described the oral pill as a “potential game changer” due to its accessibility and cost potential.

Novo Nordisk’s shares have recovered in recent weeks, driven in part by investor enthusiasm for amycretin’s dual-receptor approach and the oral format’s market expansion potential. Institutional sentiment reflects cautious optimism, with several fund managers citing the need for long-term data on cardiovascular outcomes and real-world adherence before assigning premium valuations.

As orforglipron moves closer to regulatory filing and oral semaglutide faces potential approval in the obesity indication, analysts expect a more competitive dynamic to emerge between the two drugmakers. The outcome may depend not only on efficacy, but on price, formulary access, and patient preference.

What is the long-term outlook for oral GLP-1 drugs in the obesity treatment market?

By 2027, multiple oral GLP-1 options are expected to be on the market, targeting different patient types and delivery preferences. If weight loss efficacy remains in the 15–20 percent range, and cardiovascular safety data support chronic use, oral GLP-1 therapies could displace a significant share of injectable prescriptions.

Future developments may include combination pills that integrate dual or triple agonists, or co-administration with SGLT2 inhibitors and metabolic enhancers. Partnerships and licensing deals in Asia-Pacific, Latin America, and Africa will likely play a role in globalizing access to these therapies.

While injectables like tirzepatide may retain an edge for patients with severe obesity or rapid weight reduction goals, oral therapies are poised to dominate in early-intervention scenarios, mainstream obesity management, and non-specialist care pathways.