In the New England Journal of Medicine

The anti-obesity pill is closer: duel between Lilly and Novo

Both oral weight-loss drugs show encouraging data. Competition between big pharma enters decisive phase

by Francesca Cerati

18 September 2025

Illustrazione di un peptide semaglutide (blu) legato al suo bersaglio glucagon-like peptide-1 (GLP-1, rosa chiaro). Il semaglutide è un farmaco antidiabetico e antiobesità. (Foto di Behnoush Hajian/Science Photo Li / Bha / Science Photo Library via AFP)

2' min read

Key points

Orforglipron, Lilly's weapon
Novo Nordisk's answer
A new phase of the competition
The debate in Italy

2' min read

After the success of anti-obesity injections, the challenge shifts to pills. Eli Lilly and Novo Nordisk, the two giants that pioneered the way with agonist drugs of the Glp-1 receptor, are now focusing on daily oral formulations, considered the true 'holy grail' of the industry: easier to take, store and distribute, with the potential to reach a much larger number of patients.

Orforglipron, Lilly's weapon

The full results of the phase 3 AttainN-1 study, published in the New England Journal of Medicine and presented at the Easd congress in Vienna - one of the world's largest congresses dedicated to diabetes - show that the experimental pill orforglipron reduced body weight by an average of 12.4% over 72 weeks. Almost 40% of patients treated with the highest dose lost at least 15% of their weight. Significant benefits were also observed on waist circumference, blood sugar and other cardiometabolic parameters.

Lilly also released the results of the Achieve-3 trial, which directly compared orforglipron and oral semaglutide: its candidate proved superior in both glycaemic control and weight reduction in patients with type 2 diabetes.

Novo Nordisk's response

The Danish company is not standing idly by. In the Oasis-4 study, also published in the New England Journal of Medicine, Novo Nordisk presented data on its 25 mg oral semaglutide tablet. In 64 weeks, patients lost an average of 16.6 per cent of weight, with more than a third exceeding the -20 per cent mark. Results comparable to those of the injectable version, which has conquered the global market in recent years.

Not only that. Further studies confirm the efficacy of semaglutide on the cardiovascular and psychological front as well: significant reduction in the risk of heart attack, stroke and death, but also improvement in mental wellbeing due to a decrease in so-called food noise, the obsessive thoughts related to food.

A new phase of the competition

With both drugs in the running for approval, the head-to-head between Lilly and Novo Nordisk is intensifying. The stakes are high: a potential market of millions worldwide and the possibility of transforming the therapeutic approach to obesity from a chronic disease that is difficult to manage to a condition that can be treated with a daily pill.

The debate in Italy

On the national front, the issue is also regulatory. Today in Italy, Glp-1s are reimbursed by the National Health Service only for patients with diabetes. But Undersecretary for Health Marcello Gemmato, speaking on the sidelines of an event at the Senate, opened up to the possibility of extending the prescription to non-diabetic obese patients as well: 'We are becoming aware: these drugs are excellent and could also be administered to obese patients, who have a higher risk of developing diabetes, before the disease becomes full-blown and more costly for the State. We are starting a dialogue with the Higher Institute of Health to imagine a sustainable pathway'. The game, in short, is played not only in the laboratories, but also in the palaces of the institutions.