Eli Lilly’s oral glucagon-like peptide 1 receptor agonist (GLP-1RA), orforglipron, has proven its efficacy as a maintenance therapy in patients transferred from injectable GLP-1RAs.
During the 52-week Phase III ATTAIN-MAINTAIN study (NCT06584916), the weight loss pill offered significant weight maintenance benefits over placebo when used as an adjunctive therapy alongside a healthy diet and physical activity – meeting the trial’s primary endpoint.
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This impact was seen in patients who had previously received 72 weeks of treatment with the highest dose of either Lilly’s injectable weight loss drug, Zepbound (tirzepatide), or Novo Nordisk’s competitor GLP-1RA, Wegovy (semaglutide), who were enrolled from the SURMOUNT-5 head-to-head trial (NCT05822830).
The average weight gain of patients transitioned from Wegovy to orforglipron was 0.9kg, while those transitioning from Zepbound to orforglipron experienced a 5kg weight gain after 52 weeks of maintenance therapy.
The average weight of patients transitioned from Wegovy and Zepbound before the 52-week maintenance period was 95kg and 90.9kg, respectively, with the average weight after being 95.9kg in both cohorts.
Orforglipron’s safety and tolerability profile also mirrored that seen in previous Phase III studies involving the drug, with the most common treatment-emergent adverse events (TEAEs) being mild-to-moderate and gastrointestinal in nature.
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By GlobalDataTEAE-linked discontinuations were seen in 4.8% and 7.6% transitioning from Wegovy to orforglipron and placebo, respectively. Discontinuations were also observed in 7.2% and 6.3% of patients moving from Zepbound to orforglipron and placebo, respectively.
Detailed results from this trial will be presented at an undisclosed future medical meeting.
Obesity market competition intensifies
Eli Lilly has submitted a new drug application (NDA) for orforglipron to the US Food and Drug Administration (FDA), which could see the therapy gain approval for obesity.
In preparation for the drug’s potential market debut, Eli Lilly is investing heavily in its global manufacturing footprint for orforglipron. This includes new builds in Texas and Alabama, as well as a site expansion in Puerto Rico. Outside of the US, the company is also building a new Dutch manufacturing capacity dedicated to the manufacture of the GLP-1RA.
However, it is not the only potential oral candidate on the emerging weight loss pill market, as Novo Nordisk’s Oral Wegovy (semaglutide) is currently under FDA review.
GlobalData, parent company of Pharmaceutical Technology, currently forecasts that orforglipron will claim status as a mega-blockbuster seller in 2031, bringing in sales of $13bn during that year. Analysts expect the drug to launch in 2026.
Meanwhile, a patient-based forecast predicts that oral Wegovy will reach sales of $4.4bn in 2031.
Across the broader obesity market, GlobalData senior analyst Shehroz Mahmood noted that the ATTAIN-MAINTAIN results signal an emerging trend towards maintenance and switching protocols.
Mahmood said: “With a growing pipeline of oral small molecules demonstrating promising efficacy and safety profiles, including recently Ascletis’ ASC30 and Structure Therapeutics’ aleniglipron, maintenance and switching studies could expand as companies seek differentiation in an increasingly crowded oral GLP-1RA landscape.
“This emerging pattern suggests that the obesity space is pivoting toward comprehensive treatment flexibility as a key driver of long-term adherence and market share in chronic weight management.”
Outside of the oral subcategory, Eli Lilly may have another leg up on rival Novo Nordisk, as its investigational glucose-dependent insulinotropic polypeptide (GIP), glucagon and GLP-1RA triple hormone agonist, retatrutide, recently triggered weight loss of up to 28.7% in the Phase III TRIUMPH-4 study.
In the longer term, Eli Lilly and Novo Nordisk may face competition from a newly emerging player, Pfizer, which recently acquired obesity biotech Metsera through a highly publicised bidding war with Novo.
Earlier this month, the company licensed an oral GLP-1RA asset from Fosun Pharma’s YaoPharma for $2bn, which could see Pfizer enter this lucrative market. This follows the discontinuation of its own weight loss pill, danuglipron, after a patient obtained a liver injury after receiving the therapy in a clinical trial.
