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{\"0\":\"LLY\'s orforglipron outperformed Rybelsus in reducing A1C and body weight at 52 weeks.\",\"1\":\"In ACHIEVE-3, orforglipron cut A1C by up to 2.2% at 52 weeks vs. 1.4% with Rybelsus.\",\"2\":\"Orforglipron also improved cholesterol, blood pressure and triglycerides with good tolerability.\"}
Eli Lilly (LLY - Free Report) announced positive top-line data from a late-stage head-to-head study evaluating its once-daily small molecule (non-peptide) oral GLP-1 receptor agonist, orforglipron, compared to Novo Nordisk’s (NVO - Free Report) Rybelsus (oral semaglutide), in patients with type II diabetes (T2D) inadequately controlled with metformin.
The 52-week phase III ACHIEVE-3 study evaluated orforglipron (12 mg and 36 mg) against Rybelsus (7 mg and 14 mg) across four active treatment arms to measure effects on glycemic control and weight loss. Orforglipron achieved the primary and all key secondary endpoints at 52 weeks, showing superior reductions in A1C and body weight compared to NVO’s Rybelsus. At 52 weeks, orforglipron lowered A1C by an average of 1.9% (12 mg) and 2.2% (36 mg) compared with 1.1% (7 mg) and 1.4% (14 mg) for Rybelsus, meeting the primary endpoint of the ACHIEVE-3 study.
The study also met its key secondary endpoints. Of all the patients receiving the highest orforglipron dose, 37.1% achieved A1C <5.7% at week 52, compared to 12.5% for Rybelsus at its highest dose. Eli Lilly’s orforglipron also led to superior weight loss compared to Novo Nordisk’s Rybelsus. It was observed that patients treated with the 12 mg dose of orforglipron achieved an average body weight reduction of 14.6 lbs (6.7%) while those on the 36 mg dose lost 19.7 lbs (9.2%). On the other hand, patients treated with Rybelsus 7 mg lost 7.9 lbs (3.7%) while those receiving Rybelsus 14 mg lost 11 lbs (5.3%). Thus, at the highest doses, treatment with LLY’s orforglipron led to a 73.6% greater relative reduction in body weight compared to NVO’s Rybelsus.
Additional benefits of treatment with orforglipron included improvements across key cardiovascular risk factors, including non-HDL cholesterol, systolic blood pressure and triglycerides, underscoring orforglipron’s potential as a foundational oral therapy for diabetes.
In the ACHIEVE-3 study, orforglipron was overall well-tolerated and demonstrated an acceptable safety profile, consistent with that observed in previous studies. Adverse events related to treatment were mostly gastrointestinal, which were mild to moderate in severity.
Lilly is evaluating orforglipron across seven late-stage studies in T2D and obesity. Earlier this year, the company announced positive data from another study called ACHIEVE-1 in T2D patients. In the study, orforglipron lowered A1C by an average of 1.3-1.6% across doses and also reduced weight by an average of 16lb (7.9%) at the highest dose. In April 2025, LLY announced top-line data from the ATTAIN-1 study in people with obesity (but without T2D) showing that patients taking the highest dose of orforglipron lost more than 27 pounds or 12.4% of their body weight. In the ATTAIN-2 study, announced in August, in obese adults with T2D, the highest dose (36 mg) of orforglipron delivered a weight loss of up to an average of 22.9 pounds or 10.5%.
GLP-1 therapies provide a differentiated mechanism of action that is more effective compared to existing diabetes treatments. An oral GLP-1 pill like orforglipron could offer a more convenient alternative to injectable GLP-1 therapies for patients with diabetes and obesity, marketed by Lilly and Novo Nordisk. Lilly plans to file regulatory applications for orforglipron in diabetes and obesity later this year, setting up the timeline for a potential launch in 2026.
LLY’s Competition in the GLP-1 Market Space
Novo Nordisk recently won EU approval to add cardiovascular benefits to the Rybelsus label, supported by late-stage data showing a 14% reduction in major adverse cardiovascular events compared with placebo. This makes Rybelsus the only oral GLP-1 agonist in the EU with a proven heart benefit, strengthening its preference among T2D patients. In the United States, the FDA is currently reviewing a similar label expansion for Rybelsus, with a decision anticipated later this year.
Several other companies, like Viking Therapeutics (VKTX - Free Report) , are also making rapid progress in the development of GLP-1-based candidates in their clinical pipeline. Viking Therapeutics’ dual GIPR/GLP-1 receptor agonist, VK2735, is being developed both as oral and subcutaneous formulations for the treatment of obesity. VKTX recently announced mixed top-line results from a mid-stage study evaluating the safety and efficacy of the oral formulation of VK2735, which caused the stock to drop significantly. Phase III obesity studies with the subcutaneous formulation of VK2735 have also been initiated.
LLY’s Stock Price, Valuation and Estimates
Shares of Eli Lilly have lost 1.6% so far this year compared with the industry,which has neither gained nor lost. While the stock has underperformed the S&P 500 index during the same time frame, it has outperformed the sector, as seen in the chart below.
LLY Stock Price Movement
Image Source: Zacks Investment Research
From a valuation standpoint, Lilly’s stock is expensive. Going by the price/earnings ratio, the company’s shares currently trade at 26.5 forward earnings, higher than 14.78 for the industry. However, the stock is trading much below its five-year mean of 34.54.
LLY Stock Valuation
Image Source: Zacks Investment Research
Estimates for Eli Lilly’s 2025 earnings have improved from $21.99 to $23.03 per share in the past 60 days, and estimates for 2026 earnings have improved from $30.79 to $30.95 over the same time frame.
Image: Shutterstock
LLY's Orforglipron Tops NVO's Oral Pill in Diabetes Study: What's Next?
Key Takeaways
Eli Lilly (LLY - Free Report) announced positive top-line data from a late-stage head-to-head study evaluating its once-daily small molecule (non-peptide) oral GLP-1 receptor agonist, orforglipron, compared to Novo Nordisk’s (NVO - Free Report) Rybelsus (oral semaglutide), in patients with type II diabetes (T2D) inadequately controlled with metformin.
The 52-week phase III ACHIEVE-3 study evaluated orforglipron (12 mg and 36 mg) against Rybelsus (7 mg and 14 mg) across four active treatment arms to measure effects on glycemic control and weight loss. Orforglipron achieved the primary and all key secondary endpoints at 52 weeks, showing superior reductions in A1C and body weight compared to NVO’s Rybelsus. At 52 weeks, orforglipron lowered A1C by an average of 1.9% (12 mg) and 2.2% (36 mg) compared with 1.1% (7 mg) and 1.4% (14 mg) for Rybelsus, meeting the primary endpoint of the ACHIEVE-3 study.
The study also met its key secondary endpoints. Of all the patients receiving the highest orforglipron dose, 37.1% achieved A1C <5.7% at week 52, compared to 12.5% for Rybelsus at its highest dose. Eli Lilly’s orforglipron also led to superior weight loss compared to Novo Nordisk’s Rybelsus. It was observed that patients treated with the 12 mg dose of orforglipron achieved an average body weight reduction of 14.6 lbs (6.7%) while those on the 36 mg dose lost 19.7 lbs (9.2%). On the other hand, patients treated with Rybelsus 7 mg lost 7.9 lbs (3.7%) while those receiving Rybelsus 14 mg lost 11 lbs (5.3%). Thus, at the highest doses, treatment with LLY’s orforglipron led to a 73.6% greater relative reduction in body weight compared to NVO’s Rybelsus.
Additional benefits of treatment with orforglipron included improvements across key cardiovascular risk factors, including non-HDL cholesterol, systolic blood pressure and triglycerides, underscoring orforglipron’s potential as a foundational oral therapy for diabetes.
In the ACHIEVE-3 study, orforglipron was overall well-tolerated and demonstrated an acceptable safety profile, consistent with that observed in previous studies. Adverse events related to treatment were mostly gastrointestinal, which were mild to moderate in severity.
Lilly is evaluating orforglipron across seven late-stage studies in T2D and obesity. Earlier this year, the company announced positive data from another study called ACHIEVE-1 in T2D patients. In the study, orforglipron lowered A1C by an average of 1.3-1.6% across doses and also reduced weight by an average of 16lb (7.9%) at the highest dose. In April 2025, LLY announced top-line data from the ATTAIN-1 study in people with obesity (but without T2D) showing that patients taking the highest dose of orforglipron lost more than 27 pounds or 12.4% of their body weight. In the ATTAIN-2 study, announced in August, in obese adults with T2D, the highest dose (36 mg) of orforglipron delivered a weight loss of up to an average of 22.9 pounds or 10.5%.
GLP-1 therapies provide a differentiated mechanism of action that is more effective compared to existing diabetes treatments. An oral GLP-1 pill like orforglipron could offer a more convenient alternative to injectable GLP-1 therapies for patients with diabetes and obesity, marketed by Lilly and Novo Nordisk. Lilly plans to file regulatory applications for orforglipron in diabetes and obesity later this year, setting up the timeline for a potential launch in 2026.
LLY’s Competition in the GLP-1 Market Space
Novo Nordisk recently won EU approval to add cardiovascular benefits to the Rybelsus label, supported by late-stage data showing a 14% reduction in major adverse cardiovascular events compared with placebo. This makes Rybelsus the only oral GLP-1 agonist in the EU with a proven heart benefit, strengthening its preference among T2D patients. In the United States, the FDA is currently reviewing a similar label expansion for Rybelsus, with a decision anticipated later this year.
Several other companies, like Viking Therapeutics (VKTX - Free Report) , are also making rapid progress in the development of GLP-1-based candidates in their clinical pipeline. Viking Therapeutics’ dual GIPR/GLP-1 receptor agonist, VK2735, is being developed both as oral and subcutaneous formulations for the treatment of obesity. VKTX recently announced mixed top-line results from a mid-stage study evaluating the safety and efficacy of the oral formulation of VK2735, which caused the stock to drop significantly. Phase III obesity studies with the subcutaneous formulation of VK2735 have also been initiated.
LLY’s Stock Price, Valuation and Estimates
Shares of Eli Lilly have lost 1.6% so far this year compared with the industry,which has neither gained nor lost. While the stock has underperformed the S&P 500 index during the same time frame, it has outperformed the sector, as seen in the chart below.
LLY Stock Price Movement
From a valuation standpoint, Lilly’s stock is expensive. Going by the price/earnings ratio, the company’s shares currently trade at 26.5 forward earnings, higher than 14.78 for the industry. However, the stock is trading much below its five-year mean of 34.54.
LLY Stock Valuation
Estimates for Eli Lilly’s 2025 earnings have improved from $21.99 to $23.03 per share in the past 60 days, and estimates for 2026 earnings have improved from $30.79 to $30.95 over the same time frame.
LLY Estimate Movement
Eli Lilly currently carries a Zacks Rank #3 (Hold). You can see the complete list of today’s Zacks #1 Rank (Strong Buy) stocks here.