Eli Lilly’s oral weight-loss drug matches Ozempic in trial results, signalling a shift in diabetes and obesity treatment

Eli Lilly’s experimental oral medication, orforglipron, has demonstrated weight-loss and blood sugar-lowering effects comparable to those of the blockbuster injectable drug Ozempic in a pivotal clinical trial involving individuals living with type 2 diabetes. The pharmaceutical company has announced its intention to seek regulatory approvals for orforglipron by the end of the year, aiming to introduce a new, more convenient option in a market currently dominated by injectable therapies.

News of the promising trial results sent Eli Lilly’s shares soaring by 16%, reflecting investor optimism around the drug’s commercial potential. Orforglipron is the first in a series of ongoing trials testing the oral treatment, and its success raises the prospect of a highly effective, user-friendly alternative to existing injectable weight-loss medications.

By contrast, shares of Novo Nordisk — the manufacturer of Ozempic — continued a downward trend, dropping by 7% on Thursday. Over the past year, Novo Nordisk’s U.S.-listed shares have fallen by more than 50%. In a research note, BMO Capital Markets analyst Evan Seigerman commented, “While Novo had the headstart… this first mover advantage has waned.”

The results from Lilly’s phase 3 clinical trial revealed that participants with type 2 diabetes taking orforglipron lost an average of 16 pounds — approximately 8% of their body weight — over a 40-week period. This surpasses outcomes observed with Ozempic, in which individuals on the highest dose typically lost around 6% of their body weight. Furthermore, Lilly indicated that weight loss had not plateaued by the end of the study period, suggesting that extended use could result in further weight reduction.

In terms of blood glucose control, orforglipron reduced haemoglobin A1c (HbA1c) levels — a key marker of long-term blood sugar — by an average of 1.3%. Although this falls short of Ozempic’s 2.1% reduction, the oral formulation’s overall benefits, including ease of use, are seen as significant.

Multiple pharmaceutical companies are currently in pursuit of effective oral weight-loss treatments, as global demand for such therapies accelerates. Forecasts estimate that the market for obesity drugs could exceed $150 billion in the coming years. With the publication of these results, Eli Lilly is now considered the frontrunner in the race to develop an oral alternative to injectable therapies.

Ozempic, which was first approved in 2017 for the treatment of type 2 diabetes, functions by mimicking the GLP-1 hormone — a naturally occurring hormone in the gut that helps regulate appetite and blood sugar. Eli Lilly’s existing injectable medication, tirzepatide, is marketed under the brand names Mounjaro (for diabetes) and Zepbound (for weight management). Tirzepatide mimics both GLP-1 and a second hormone, GIP, and has achieved weight reductions of up to 22% over 72 weeks in clinical studies.

Unlike tirzepatide, orforglipron targets only the GLP-1 pathway. However, its distinction lies in its composition: it is a synthetic small molecule, not a peptide-based drug. This molecular structure allows for simpler and more scalable manufacturing, which could enable broader access to effective weight-loss treatment.

“Readily manufactured” oral agents like orforglipron may dramatically expand access to treatment, particularly among individuals who face barriers to injectable therapies. Lilly also reported that orforglipron’s safety profile was consistent with other GLP-1 receptor agonists, easing concerns that side effects could hinder its commercial viability.

“The data is fantastic from an efficacy standpoint,” said Kevin Gade, Chief Operating Officer at investment firm Bahl & Gaynor, which holds shares in Lilly.

The company has also confirmed that it will publish results from another trial focused specifically on weight management later this year. Regulatory submissions for approval to treat obesity are expected before the year’s end, with an application for diabetes to follow in 2026.

“While this trial alone is very good, this just bodes extremely well for their trial in obesity patients,” Gade added.

Regarding side effects, the trial found that 13% to 18% of participants experienced nausea at varying doses, compared to 2% of those given a placebo. Diarrhoea occurred in 19% to 26% of individuals on orforglipron, and vomiting affected between 5% and 14%, depending on the dose.

“These results firmly validate the tolerable profile of orforglipron,” Seigerman noted in his analysis.

Importantly, Lilly reported no signs of liver-related safety issues in its trial. This stands in contrast to Pfizer’s recent announcement that it would halt development of its experimental weight-loss pill, danuglipron, after a participant in one of its trials experienced potential drug-induced liver injury — a side effect which resolved after discontinuing the medication.

Lilly did state that 8% of patients on the highest orforglipron dose discontinued treatment due to adverse events. However, reductions in HbA1c across all tested doses ranged between 1.3% and 1.6%, reinforcing the drug’s effectiveness in managing blood glucose levels.

The trial’s multi-dose data revealed that individuals taking orforglipron daily achieved the following average reductions in body weight over 40 weeks:

• 4.7% reduction with a 3 mg dose
• 6.1% reduction with a 12 mg dose
• 7.9% reduction with a 36 mg dose

By comparison, individuals given a placebo experienced a 1.6% reduction in body weight.

Lilly has expressed confidence in its ability to meet global demand for orforglipron, should regulatory approvals be granted. The company noted that it recorded $550 million in drug-related inventory in its February financial statements, underscoring its readiness to launch the medication on a global scale.

If successful, orforglipron could become a landmark treatment option for people living with type 2 diabetes and obesity — offering meaningful weight loss in a daily oral format, with manufacturing and access advantages that may redefine the future of obesity care.