Eli Lilly and Company LLY announced that a phase III study, ACHIEVE-4, evaluating its newly approved oral GLP-1 weight-loss pill Foundayo (orforglipron), for treating patients with type II diabetes and obesity who also carry elevated cardiovascular risk, met its primary endpoint. Overall, the oral GLP-pill demonstrated cardiovascular safety, strong glucose-lowering, substantial weight loss, and a potential mortality benefit in the study. The study enrolled more than 2,700 participants across 15 countries.<\/p>\n
Foundayo was approved by the FDA for treating obesity and launched earlier this month. It is now widely available via LillyDirect and telehealth platforms as well as across U.S. retail pharmacies. For the type II diabetes indication, based on the ACHIEVE-4 data, Lilly plans to file regulatory applications in the United States by the end of the second quarter under a priority review program.<\/p>\n
The primary outcome of the ACHIEVE-4 study focused on major adverse cardiovascular events (MACE-4), a composite endpoint including cardiovascular death, heart attack, stroke, and hospitalization for unstable angina. Foundayo successfully met its primary goal by demonstrating non-inferiority to insulin glargine, a standard-of-care comparator in reducing MACE events. Foundayo reduced the risk of MACE-4 events by 16% and MACE-3 events by 23% compared to insulin glargine. While this reduction was not statistically significant for superiority, it is clinically meaningful because it demonstrates that the drug does not increase cardiovascular risk\u2014a key regulatory requirement for diabetes therapies\u2014and trends toward benefit. A notable finding was a 57% reduction in all-cause mortality versus insulin glargine in a pre-planned analysis, suggesting potential broader survival benefits, though this result was not adjusted for multiplicity.<\/p>\n
Beyond cardiovascular outcomes, Foundayo delivered superior glycemic control, reducing A1C by 1.6% versus. 1.0%, and showed a substantial weight loss benefit of 8.8%, compared to weight gain with insulin, with effects sustained through 104 weeks.<\/p>\n
The drug also improved multiple cardiometabolic risk markers, including cholesterol, blood pressure, triglycerides, and inflammation (hsCRP), reinforcing its holistic benefit profile. Safety was consistent with the GLP-1 class, with mainly gastrointestinal side effects and no liver safety issues identified.<\/p>\n
Oral pills are expected to be a more convenient alternative to the once-weekly injectable GLP-1 obesity treatments like Lilly\u2019s Zepbound and rival Novo Nordisk NVO Wegovy. Oral pills may significantly lower treatment burden and potentially broaden patient adoption versus injections. They can also be manufactured at scale to meet global demand, which, in turn, can drive billions in additional sales.<\/p>\n
The data from the ACHIEVE 4 study position Foundayo as a promising oral alternative to insulin with meaningful metabolic and potential cardiovascular advantages.<\/p>\n
Lilly\u2019s stock has risen 7.6% in the past year compared with the industry\u2019s increase of 18.6%.<\/p>\n
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Novo Nordisk had gained approval for an oral version of its obesity drug, Wegovy, in December 2025 and launched the pill in January 2026. The Wegovy pill gave NVO a first-to-market advantage and will initially bring in additional revenues. However, we believe Lilly may be able to close the gap quickly now that the FDA has approved Foundayo.<\/p>\n
Earlier this week, the FDA instructed Lilly to collect additional safety data from ongoing studies on Foundayo to understand potential risks related to the use of the pill, including risks of liver injuries and MACE events.<\/p>\n
In the letter, the FDA also asked Lilly to track cases of a rare type of thyroid cancer in the United States for at least 15 years. The FDA also asked for more information about delayed gastric emptying associated with the use of Foundayo. The FDA\u2019s need for these post-marketing safety data raised concerns that it may affect decision-making among doctors, payers and patients and hurt Foundayo’s commercial prospects as well as its competitive positioning against NVO\u2019s Wegovy pill.<\/p>\n
However, the data from the ACHIEVE-4 study could address some of the FDA\u2019s concerns as it successfully demonstrated the drug\u2019s cardiovascular benefits. Also, so far in all clinical studies, including ACHIEVE-4, the use of Foundayo has not been associated with any drug-induced liver injury.<\/p>\n
While Lilly and Novo Nordisk currently dominate the obesity space, smaller biotechs like Structure Therapeutics GPCR and Viking Therapeutics VKTX are also developing oral GLP-1 drugs for treating obesity.<\/p>\n
Viking Therapeutics\u2019 dual GIPR\/GLP-1 receptor agonist, VK2735, is being developed both as oral and subcutaneous formulations for the treatment of obesity. \u00a0Viking plans to advance oral VK2735 into phase III development for obesity in the third quarter of 2026.<\/p>\n
Structure Therapeutics\u2019 phase II ACCESS study on its orally GLP-1 RA, aleniglipron, demonstrated significant weight loss across all doses. Structure Therapeutics expects to initiate the late-stage program of aleniglipron in obesity in the second half of 2026.<\/p>\n
Lilly has a Zacks Rank #3 (Hold) stock. You can see the complete list of today\u2019s Zacks #1 Rank (Strong Buy) stocks here.<\/p>\n
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