
Eli Lilly's Obesity Pill Appears to Work as Well as Injected GLP-1s
Jun 21, 2025 9:01 AM New data from a Phase 3 trial show that the daily anti-obesity pill may be as safe and effective as drugs like Mounjaro and Ozempic for weight loss and lowering blood sugar. PHOTO-ILLUSTRATION: WIRED STAFF; GETTY IMAGES
Eli Lilly's daily anti-obesity pill orforglipron appears to be as good at spurring weight loss and lowering blood sugar in diabetes patients as popular injectable GLP-1 drugs like Ozempic, according to new data from a Phase 3 trial. The results were announced today at the annual meeting of the American Diabetes Association.
Eli Lilly is the maker of the blockbuster GLP-1 drug tirzepatide, approved as Mounjaro for type 2 diabetes and Zepbound for chronic weight management and obstructive sleep apnea. Like Novo Nordisk's Ozempic and Wegovy, both of Eli Lilly's tirzepatide drugs are injected on a weekly basis. But some patients have a fear of needles or would prefer to take a pill out of convenience.
'What we see is that the efficacy, safety, and tolerability are really consistent with the very best injectable GLP-1s,' says Kenneth Custer, president of cariometabolic health at Eli Lilly, of the company's experimental pill. 'We think this is a big deal.' The company plans to seek regulatory approval for orforglipron for weight management by the end of this year and for the treatment of type 2 diabetes in 2026.
The 40-week trial tested three doses of orforglipron—3 milligrams, 12 milligrams, and 36 milligrams—against a placebo in 559 patients with type 2 diabetes. All three doses were effective at lowering blood sugar, while the middle and highest doses showed clinically meaningful and statistically significant reductions in body weight. The highest dose of orforglipron led to an average weight loss of 7.9 percent, or 16 pounds—comparable to the amount of weight loss seen over the same period in trials of semaglutide and tirzepatide. Eli Lilly is studying the pill in a longer study in people who are overweight or have obesity to see if the weight loss continues.
In the current trial, participants took the pill once a day with no food or water restrictions. Those who were randomly assigned to orforglipron started the study at a dose of 1 milligram a day and slowly increased the dose at four-week intervals. Current GLP-1 drugs are gradually stepped up in dose as well to minimize potential side effects.
Orforglipron showed similar gastrointestinal side effects as other GLP-1 drugs, with the most common being diarrhea, nausea, indigestion, and constipation. Between 4 and 8 percent of participants across the different dosing groups dropped out because of side effects, while 1 percent in the placebo group discontinued the study.
An oral version of semaglutide, sold under the brand name Rybelsus, has been on the market since 2019 but is not approved for weight management and isn't as effective for weight loss as injectable GLP-1s. A pill specifically for obesity would give patients more treatment options and potentially make these drugs more accessible.
Pills are typically less expensive to manufacture, and they can be mass-produced more easily, making them less prone to shortage. (Injected GLP-1 drugs were in shortage until recently.) Pills can also be transported more readily. Current GLP-1 injector pens need to be shipped and stored in a refrigerator to maintain their potency. A GLP-1 pill wouldn't need sophisticated cold-chain distribution and storage, meaning it could be sold in countries that don't have that infrastructure.
'With orforglipron offering additional advantages such as the elimination of strict pre-dosing requirements, potential lower cost, and easier storage, it will be important to see whether these features lead to even greater adherence,' says Priya Jaisinghani, a diabetes and obesity medicine specialist at NYU Langone. 'Like most chronic therapies, GLP-1s are most effective when used consistently, so a formulation that encourages long-term use could have a meaningful impact on patient outcomes.'
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Novo Nordisk A/S: CagriSema 2.4 mg / 2.4 mg demonstrated 22.7% mean weight reduction in adults with overweight or obesity in REDEFINE 1, published in New England Journal of Medicine
By GlobeNewswire Published on June 22, 2025, 18:00 IST Data presented simultaneously at the American Diabetes Association's ® 85 th Scientific Sessions, showed mean weight reduction in the highest range of efficacy observed with existing weight loss interventions 1 85 Scientific Sessions, showed mean weight reduction in the highest range of efficacy observed with existing weight loss interventions When adhering to treatment, weight loss of ≥5%, ≥20%, ≥25%, and ≥30% was observed in 97.6%, 60.2%, 40.4% and 23.1% of patients respectively at 68 weeks 1 * The REDEFINE clinical programme is ongoing to further investigate efficacy and safety of CagriSema, including recently initiated REDEFINE 112 Bagsværd, Denmark, 22 June – Today, The New England Journal of Medicine (NEJM) published results from Novo Nordisk's phase 3 REDEFINE 1 trial evaluating the efficacy and safety of investigational CagriSema plus lifestyle interventions for weight loss in adults with obesity or overweight who have a weight-related medical complication and without diabetes.1 REDEFINE 1 met its co-primary endpoints and achieved statistically significant and clinically meaningful weight loss at 68 weeks in patients taking CagriSema versus placebo.1 These data, along with the related phase 3 REDEFINE 2 study conducted in adults with overweight or obesity and type 2 diabetes, were presented today during a scientific symposium at the American Diabetes Association's (ADA) 85th Scientific Sessions and published in NEJM . 'In REDEFINE 1, participants saw significant and clinically meaningful weight loss under a protocol that allowed investigators to maintain patients on a submaximal dose if deemed best for the patient. We also witnessed low, single-digit discontinuation rates due to adverse events in both REDEFINE 1 and 2,' said Martin Holst Lange, executive vice president and head of Development at Novo Nordisk. 'These results reinforce our confidence in CagriSema, and we continue to study the potential of this combination through the REDEFINE trials.' CagriSema is an investigational product that combines the GLP-1 RA, semaglutide, with an amylin analogue, cagrilintide. The REDEFINE 1 trial found that treatment with CagriSema resulted in greater weight loss of 22.7% at 68 weeks versus 2.3% in the placebo group if all patients adhered to treatment.1* When evaluating the treatment effect regardless of adherence, those treated with CagriSema achieved statistically significant weight loss of 20.4% at 68 weeks versus 3.0% for the placebo group.1** In addition, a supportive secondary analysis showed that half (50.7%) of trial participants with obesity treated with CagriSema reached the threshold for non-obesity (BMI < 30 kg/m2) at the end of treatment, from a mean BMI of 38 kg/m2 at the start of treatment. In the placebo group,10.2% reached that threshold at 68 weeks.1 Select confirmatory secondary endpoints showed that if all participants adhered to treatment 40.4% of those receiving CagriSema achieved a body weight reduction of ≥25%.* Additionally, 23.1% lost ≥30% of their body weight.1* When applying the treatment policy estimand, 34.7% of participants treated with CagriSema achieved ≥25% body-weight reduction and 19.3% achieved ≥30% body-weight reduction.1** In a prespecified analysis of 252 participants, the relative reduction in fat and lean soft-tissue mass from baseline to week 68 was -35.7% (fat mass) and -14.4% (lean soft-tissue mass) for those treated with CagriSema versus –5.7% and –4.3% for the placebo group, respectively.1 'In REDEFINE 1, CagriSema provided weight loss in the highest range of efficacy observed with existing weight loss interventions,' said lead investigator Timothy Garvey, MD, professor of medicine and director of the Diabetes Research Center at the University of Alabama at Birmingham. 'Investigators were allowed some flexibility in dose adjustments to balance efficacy and safety, but regardless of dose adjustments participants lost significant weight. These findings are relatable to clinical practice, where dosing is often adjusted based on individual needs and clinical judgement.' Safety data generated in the REDEFINE 1 and 2 trials were comparable with the GLP-1 RA class. 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Most recently, Novo Nordisk initiated the REDEFINE 11 trial with the first patient visit occurring in early June 2025. REDEFINE 11 will explore further weight loss potential and safety of CagriSema 2.4 mg / 2.4 mg through a longer trial duration and other protocol changes compared to REDEFINE 1 and 2. * Based on the trial product estimand; this estimand estimates what the effect would be if all participants adhered to treatment ** Based on the treatment policy estimand: treatment effect regardless of treatment adherence About CagriSema CagriSema is being investigated by Novo Nordisk as a once-weekly subcutaneous injectable treatment for adults with overweight or obesity (REDEFINE programme) and as a treatment for adults with type 2 diabetes (REIMAGINE programme). CagriSema is a fixed-dose combination of a long-acting amylin analogue, cagrilintide 2.4 mg and semaglutide 2.4 mg. About the REDEFINE clinical trial programme REDEFINE is a phase 3 clinical development programme with once-weekly subcutaneous CagriSema in obesity. REDEFINE 1 and REDEFINE 2 have enrolled approximately 4,600 adults with overweight or obesity. REDEFINE 1 was a double-blind, placebo-and active-controlled 68-week efficacy and safety phase 3 trial of once-weekly CagriSema, cagrilintide 2.4 mg and semaglutide 2.4 mg versus placebo in 3,417 adults with obesity or overweight with one or more comorbidities and without type 2 diabetes. REDEFINE 2 was a double-blind, randomized, placebo- and controlled 68-week efficacy and safety phase 3 trial of once-weekly CagriSema versus placebo in 1,206 adults with type 2 diabetes and either obesity or overweight. Multiple REDEFINE clinical trials are currently underway including: REDEFINE 3, an event-driven cardiovascular outcomes phase 3 trial; REDEFINE 4 an 84-week head-to-head efficacy and safety phase 3 trial of once-weekly CagriSema versus once-weekly tirzepatide; and REDEFINE 11, a phase 3 trial with longer duration and other protocol changes compared to REDEFINE 1 and 2. About obesity Obesity is a serious chronic, progressive, and complex disease that requires long-term management.4–6 One key misunderstanding is that this is a disease of just lack of willpower, when in fact there is underlying biology that may impede people with obesity from losing weight and keeping it off.4,6 Obesity is influenced by a variety of factors, including genetics, social determinants of health, and the environment.7,8 About Novo Nordisk Novo Nordisk is a leading global healthcare company founded in 1923 and headquartered in Denmark. Our purpose is to drive change to defeat serious chronic diseases built upon our heritage in diabetes. We do so by pioneering scientific breakthroughs, expanding access to our medicines, and working to prevent and ultimately cure disease. Novo Nordisk employs about 77,400 people in 80 countries and markets its products in around 170 countries. For more information, visit , Facebook , Instagram , X , LinkedIn and YouTube . Contacts for further information References: Garvey WT, Blüher MD, Contreras CKO, et al. CagriSema in Adults with Overweight or Obesity. New England Journal of Medicine 2025. doi: 10.1056/NEJMoa2502081 A Research Study to Look at How Well CagriSema Helps People Living With Obesity Lose Weight and Maintain Weight Loss in the Long-term. Last Accessed: June 2025. Available at: Davies MJ, Harpreet S, Bajaj MD, et al. CagriSema in Adults with Overweight or Obesity and Type 2 Diabetes. New England Journal of Medicine 2025. Kaplan LM, Golden A, Jinnett K, et al. Perceptions of barriers to effective obesity care: results from the national action study. Obesity . 2018;26(1):61-69. Bray GA, Kim KK, Wilding JPH; World Obesity Federation. Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Rev . 2017;18(7):715-723. Garvey WT, Mechanick JI, Brett EM, et al. American association of clinical endocrinologists and American College of Endocrinology comprehensive clinical practice guidelines for medical care of patients with obesity. Endocr Pract . 2016;22 (Suppl 3):1-203. Centers for Disease Control and Prevention. Adult obesity facts. Last accessed: June 2025. Available at: World Obesity Federation. World Obesity Atlas 2023. Last accessed: June 2025. Available at: Attachment Disclaimer: The above press release comes to you under an arrangement with GlobeNewswire. Business Upturn takes no editorial responsibility for the same. Ahmedabad Plane Crash GlobeNewswire provides press release distribution services globally, with substantial operations in North America and Europe.

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