Eli Lilly and Company (LLY Quick QuoteLLY - Free Report) presented new efficacy data from studies of its marketed and investigational metabolic medicines at the annual European Association for the Study of Diabetes (EASD) conference. Foundayo (orforglipron), a once-daily oral GLP-1 receptor agonist, is FDA-approved for chronic weight management in adults with obesity or certain adults with overweight and weight-related medical problems. Eli Lilly also reported results for EloraTZP, an investigational combination of eloralintide, a selective amylin receptor agonist, and LLY’s blockbuster obesity drug, Zepbound (tirzepatide), a dual GIP and GLP-1 receptor agonist, being developed for people with obesity or overweight and type II diabetes (T2D).

LLY’s Foundayo Shows Cardiovascular Safety in Diabetes Study

Eli Lilly reported detailed results from the phase III ACHIEVE-4 study, its largest and longest study of Foundayo in adults with T2D and obesity or overweight at increased cardiovascular risk. Foundayo demonstrated a non-inferior risk of major adverse cardiovascular events (MACE) versus titrated insulin glargine, meeting the primary objective.

The risk of MACE-4, including cardiovascular death, heart attack, stroke or hospitalization for unstable chest pain, was 16% lower with Foundayo compared with insulin glargine. The risk of MACE-3, including cardiovascular death, heart attack or stroke, was 23% lower for Foundayo vs. insulin glargine. In pre-planned analyses, the risk of cardiovascular death was 53% lower and that of all-cause death was 57% lower with Foundayo compared with insulin glargine.

Foundayo also delivered stronger glycemic and weight outcomes compared with insulin glargine. At 52 weeks, A1C declined 1.6% versus 1%, while body weight fell 8.8% versus a 1.7% increase, respectively. At 104 weeks, 54.6% of Foundayo-treated patients achieved an A1C of 6.5% or lower and 35.9% achieved at least 10% weight loss compared with 23.8% and 3.4%, respectively, for insulin glargine.

Foundayo also improved cardiometabolic measures, including waist circumference, systolic blood pressure, triglycerides, non-HDL cholesterol and hsCRP. Kidney measures favored Foundayo, with a smaller decline in eGFR and greater reduction in albuminuria. The safety profile remained consistent with prior studies, with gastrointestinal events among the most common and 10.6% discontinuing due to adverse events.

Foundayo, with its current approved indication, competes directly with Novo’s (NVO Quick QuoteNVO - Free Report) oral Wegovy (semaglutide), which is also approved for chronic weight management. Novo also markets two oral semaglutide-based GLP-1 medicines, Ozempic and Rybelsus, for T2D. Meanwhile, Lilly has submitted a regulatory filing to the FDA seeking approval of Foundayo for the treatment of T2D, with the application currently under review. The oral GLP-1 race between Lilly and Novo is intensifying as both companies expand their portfolios beyond injectable therapies, with convenience and efficacy emerging as key areas of competition.

Smaller biotechs are also entering the GLP-1 space, such as Viking Therapeutics (VKTX Quick QuoteVKTX - Free Report) , which is advancing VK2735, a dual GLP-1/GIP agonist, in both oral and subcutaneous formulations for the treatment of obesity. Viking recently reported positive top-line results from a subcutaneous maintenance study, with patients maintaining up to 97% of their prior weight loss on every-other-week dosing and up to 90% on monthly dosing over the 12-week maintenance period. Viking plans to advance oral VK2735 into phase III development for obesity in the fourth quarter of 2026.

LLY’s EloraTZP Delivers Greater Weight Loss and A1C Reduction

Eli Lilly also reported positive 48-week results from a phase IIb study of EloraTZP in adults with obesity or overweight and T2D. In the mid-stage study, all EloraTZP combinations met the primary and secondary endpoints, delivering substantial weight loss and A1C reductions at 48 weeks. The results were presented at the annual EASD conference.

Per the data readout, the highest-dose combination, 9 mg of eloralintide plus 15 mg of Zepbound, reduced body weight by 23.3% (54.1 pounds) at 48 weeks compared with 14.8% (34.4 pounds) for Zepbound 15 mg alone. A1C declined 2.9% with the combination versus 2.4% with Zepbound. Eloralintide monotherapy reduced weight by up to 12.3% (28.6 pounds) and A1C by up to 1.4% at the 6mg dose level.

The results underscore Eli Lilly’s strategy of targeting multiple metabolic pathways with EloraTZP. By simultaneously activating GIP, GLP-1 and amylin signaling, the combination is designed to help regulate hunger and blood sugar. Eli Lilly is evaluating whether the candidate can deliver greater weight loss and glucose control than Zepbound alone. Gastrointestinal adverse events were the most common and were generally mild to moderate, particularly during dose escalation.

Eloralintide is already in phase III development for obesity, while Eli Lilly plans to begin phase III studies of an optimized EloraTZP co-formulation by the end of 2026.

LLY’s Ebglyss Shows Rapid Hand and Foot Skin Clearance

Separately, Eli Lilly reported positive phase IIIb ADtouch data for Ebglyss (lebrikizumab-lbkz) supporting a potential U.S. label expansion to include localized atopic dermatitis with moderate-to-severe hand and foot involvement.

Ebglyss is an IL-13 inhibitor that selectively blocks IL-13 signaling, a key driver of skin inflammation, itch and barrier dysfunction in atopic dermatitis. It is currently approved in the United States for adults and children aged 12 years and older who weigh at least 40 kilograms with moderate-to-severe atopic dermatitis that is not adequately controlled with prescription topical therapies or when such therapies cannot be used. The drug can be used with or without topical corticosteroids.

The phase IIIb ADtouch study met its primary and secondary endpoints, with 53% of patients treated with Ebglyss monotherapy achieving clear or almost clear hands and feet at week 16 versus 27% with placebo. Skin clearance was evident by week four, with 17% achieving the endpoint versus 6% for placebo. Ebglyss also produced early improvements in itch and pain.

At week 16, 57% of Ebglyss-treated patients with relevant baseline itch achieved a four-point or greater improvement versus 19% with placebo. For pain, 59% achieved the same level of improvement versus 19% with placebo. Patient satisfaction also improved, with 77% reporting satisfaction with hand clearance versus 40% with placebo.

Safety findings were consistent with the known profile of Ebglyss, with no new signals reported. Eli Lilly has submitted the ADtouch data to the FDA and plans to seek submissions with select global regulatory authorities for a potential label update to include localized atopic dermatitis with moderate-to-severe hand and foot involvement. The company holds exclusive rights to develop and commercialize Ebglyss in the United States and worldwide outside Europe. Almirall has licensed rights to develop and commercialize the drug for dermatology indications, including atopic dermatitis, in Europe.