Opinion – Bruno Gualano: A revolution in the treatment of obesity

Obesity treatment encompasses diets, exercises, a few medications that help control appetite and, in more serious cases, bariatric surgery. None of this seems to be enough to prevent almost 1 billion people around the world from suffering from this condition.

But the feeling of a lost war gave way with the arrival of new peptides from the incretin class —dubbed in Brazil as slimming pens, given that they are injectable. Some specialists believe that this is a true revolution in the treatment of obesity. Are there reasons for such excitement?

Let’s start with the glass half full. These new peptides, which “mimic” intestinal hormones capable of increasing insulin secretion and post-feeding satiety, have passed the test of good clinical trials. And with praise.

In overweight or obese people, loss of body weight under chronic use (about a year and a half) of semaglutide (Wegovy, from Novo Nordisk, approved by Anvisa) or tirzepatida (Mounjaroda, from Eli Lilly, in the process of being approved by the FDA) has been of the order of 17% and 20%, respectively.

And that’s not much. Current drugs do not exceed the 5% mark. Exercise, at best, promotes modest weight loss of debatable clinical significance (although it generates other valuable therapeutic effects, as discussed here). In terms of weight reduction, only bariatric surgery, an invasive intervention with limited access to the population, seems to be comparable to these new drugs.

Another piece of good news comes from the fact that the excellent results obtained with semaglutide in adults extend to obese adolescents. In a recently published study, 73% of medicated young people achieved a body weight loss greater than 5%, against only 18% of those who received placebo. The drug produced an average weight loss of 15% (versus 2% in the placebo group). A similar clinical trial with tirzepatide is ongoing, with results expected in 2027.

In addition to promoting extraordinary weight loss, the new drugs bring other benefits (many of them derived from weight reduction itself): decrease in circulating sugar levels, improvement in the lipoprotein profile (increase in HDL, decrease in LDL and triglycerides), attenuation of systemic inflammation and blood pressure control. As can be seen, there are good reasons to justify the euphoria.

There are, however, practical issues that dampen enthusiasm. Here’s the water in the beer.

In the most robust clinical trials, participants treated with the new drugs followed, concomitantly, a program of physical activity and healthy eating. Without the effective behavior change, would the weight loss be the same? Or: when the medication is discontinued, would the benefits be maintained without adopting a healthy lifestyle?

Everything indicates no. One study reported recovery of two-thirds of lost weight just one year after discontinuing combined treatment with semaglutide, exercise, and diet. The challenge of maintaining gains, which haunts professionals and patients alike, extends to new drugs.

In studies involving participants with type 2 diabetes and overweight, the most common adverse events (nausea, vomiting, abdominal pain, constipation, and diarrhea) are mild. Hence, it cannot be concluded that the unrestricted use of these drugs is safe for people with no indication of weight loss. More movement and better nutrition remain the preferred “treatments” for love handles, breeches, and other cosmetic woes.

In countries like the United States and Australia, a disastrous effect of the glamorization of these drugs can already be observed: people who really need them cannot find them. Added to this is the high cost of medication —treatment with Ozempic, for example, costs around BRL 12,000 a year.

These can be important obstacles to the broad and equitable access of the population to treatment.

Despite the gaps and difficulties posed, the revolutionary potential that these new drugs present must be recognized. It is not about denying the lifestyle as a pillar of health, but about celebrating the introduction of an allied therapy that is highly capable of combating obesity. The silver bullet doesn’t exist yet, but our arsenal has gained an extra weapon.