Semaglutide & co.: independent studies on long-term effects are needed

Three systematic reviews commissioned by the WHO bring some order to the excessive amount of studies on the “miraculous” effects of injectable weight loss drugs, GLP-1 receptor agonists.

According to the analyzes – published in the Cochrane Library, considered an authority in the review processes of scientific literature on the effects of health interventions – semaglutide, liraglutide and tirzepatide are very effective tools in the fight against obesity, but there are still three critical points to work on before their large-scale diffusion can be hoped for.

So what are these unsolved problems? Studies on their long-term effects are lacking; they are still not economically accessible; and the research concerning them lacks independence.

Semaglutide, tirzepatide and liraglutide mimic the action of the hormone GLP-1, naturally present in the intestine, which slows digestion and helps you feel full longer. Introduced in the mid-2000s as drugs against diabetes, the medicines of this family are experiencing a “second youth” as tools for weight control in patients suffering from obesity, even without diabetes, combined with a careful diet and physical activity.

All three studies found that these drugs helped achieve significant weight loss within one to two years compared to a placebo, a result that the authors of the work call “an exciting moment after decades of failed attempts to find effective treatments for people living with obesity.”

Tirzepatide led to a reduction of approximately 16% in weight after 12-18 months, with effects that would appear to last for 3.5 years; semaglutide, to the loss of approximately 11% of weight after 6-15 months, with evident benefits even after 2 years even if – compared to the other two – the drug led to gastrointestinal disorders more often. Finally, liraglutide allowed a reduction in body weight by 4-5%, with limited benefits two years after the end of treatment.

However, the analyzes did not reveal, despite what several studies have asserted so far, differences between the three drugs and the placebo when it came to the prevention of major cardiovascular events, mortality from any cause, or improvement in quality of life.

Having established the benefits, the fact remains that these medicines still remain a “luxury” solution, an aesthetic intervention for millionaires, and that the price still represents an important obstacle to their use on a larger scale.

This applies especially to semaglutide and tirzepatide, because the patent protection of liraglutide has expired and the drug is now more accessible thanks to generic versions. The same fate will befall semaglutide in 2026 in some large markets (China, India, Brazil, Canada and Turkey): will this be an opportunity for a broader discussion on the accessibility of this medicine?

Obesity is rapidly increasing in developing countries: globally, excess weight has overtaken underweight as the most common form of malnutrition among children and adolescents. Not addressing the costs of injectable drugs to fight obesity means making health inequalities even deeper.

Furthermore, most of the studies so far have been carried out in middle- and high-income countries, while very little is known about the effects of semaglutide, liraglutide and tirzepatide in contexts with different eating habits, body composition and health problems compared to those typical of Western and industrialized countries.

Most of the studies considered by the three reviews were financed by the same pharmaceutical companies producing the drugs, which also took care of the experimental setup, analyzes and communication of the research results. The benefits of injectable weight loss medicines would be even more appreciable if independent studies and not jobs at risk of conflicts of interest highlighted them. As the authors point out, “more independent studies are needed, which take the public health point of view.”