New pills, genetics and artificial intelligence are on the way to treat obesity

For years, the question has been how much weight to lose. At the national congress of the Italian Society for Obesity (SIO), which has just concluded in Palermo, the question has shifted to: which treatment, for which person, and for how long. Because the medicines are available and they work, but in real life patients stop taking them soon after. The starting point is a silent emergency: according to the Passi surveillance programme, in 2024–2025, 43 per cent of Italian adults were overweight, with over 10 per cent classified as obese. Law 149 of 2025 recognised it as a chronic disease, but ‘we still need to learn how to identify it and manage it as such’, observes SIO president Silvio Buscemi . This is also because the scales tell us very little: at the University of Palermo, out of 495 students, 19 of the 46 with metabolic abnormalities had a normal BMI; at the Luigi Vanvitelli University of Campania, rare genetic variants were found in over half of 400 children with severe early-onset obesity. “Weight is a surface indicator: it measures body mass, but does not reveal the underlying biology,” explains Buscemi.

The range of treatment options has expanded rapidly. In 2015, liraglutide became the first GLP-1 agonist to be approved for obesity; this was followed by semaglutide and tirzepatide – the latter of which also acts on the GIP receptor – both of which are administered weekly. According to Uberto Pagotto, an endocrinologist in Bologna, the guidelines recommend treatment from a BMI of 30 and from a BMI of 27 in cases of overweight with a comorbidity: ‘Today, clinicians can tailor their choice based on the degree of obesity, comorbidities and the patient’s goals.’ But efficacy alone is not enough. “It is disappointing to see that real-world studies show an incredibly short duration of treatment adherence for therapies that should, in fact, be long-term,” says Paolo Sbraccia, an internist at Tor Vergata University in Rome. Cost is a factor, as these drugs are not reimbursed by the National Health Service in Italia, as is the need for injection. It is on this point that the market has begun to shift towards oral tablets. In the United States, Novo has taken the lead: oral semaglutide was approved in December and launched in January. Lilly, on the other hand, is banking on the orforglipron tablet, approved in April, which can be taken at any time without restrictions, whilst Novo’s version must be taken in the morning, half an hour before food, water or other medicines. Neither is yet available in Italia, but they are expected in 2027.

But be careful when making comparisons, as these are different molecules. Oral semaglutide is a peptide that withstands stomach acid thanks to Snac, its molecular ‘bodyguard’. Orforglipron is a small, non-peptide molecule which, as explained by Massimiliano Caprio of the San Raffaele University, ‘is absorbed very easily at any time of day, regardless of food or water intake’. The figures on efficacy do not overlap: in the Oasis 4 study, oral semaglutide at 25 mg reduced weight by 17 per cent compared with 2.7 per cent for the placebo; in Attain-1, involving over 3,100 adults, orforglipron achieved a weight loss of -12.4 per cent compared with -0.9 per cent at 72 weeks. These are different studies and therefore not directly comparable: an indirect comparison sponsored by Novo (Orion) reports more discontinuations due to adverse events for orforglipron, whilst Achieve-3, in people with type 2 diabetes, shows it to be superior to oral semaglutide at 7–14 mg.

The key will be who manages to keep patients on treatment. According to Sbraccia, the tablet is better accepted by those who are just starting out and are hesitant about injections: it can make it possible to start treatment sooner. ‘Instead of waiting for the disease to progress to the point where losing tens of kilos becomes very difficult, it would be better to intervene sooner.’

The final frontier is artificial intelligence: Sio, the Policlinico di Palermo and Humanitas are collecting clinical, metabolic and genomic data to classify patients, predict complications and, one day, build a ‘digital twin’ on which to simulate treatments. ‘AI can help us move from treating obesity to treating that specific person with obesity,’ says Buscemi. But it needs to be validated and must support the doctor, not replace them.