The EVISAP group (Cochrane Balearic Islands) has published a new article that provides an in-depth analysis of GLP-1 receptor agonist drugs used in the treatment of obesity, as well as the mechanisms behind their effectiveness and the unanswered questions regarding their long-term impact.

The article, authored by Dr. Rocío Zamanillo Campos, a postdoctoral researcher at IdISBa and dietitian-nutritionist, reviews the available evidence on these medications — increasingly present both in clinical practice and public debate — and raises a key question: is their effect on weight loss truly due to metabolic improvements, or mainly to a reduction in food intake?

A therapeutic success with nuances

GLP-1 drugs, used for years in the treatment of type 2 diabetes, have shown a significant reduction in body weight while treatment is ongoing. According to available clinical trials, weight loss ranges from 4% to 16% depending on the drug.

However, these studies have important limitations, such as the lack of control over dietary intake and the absence of data on what happens when treatment is stopped, which affects the interpretation of the results.

Weight regain: a key issue

One of the central topics addressed in the article is what happens when medication is discontinued. Evidence indicates that weight is regained, often more rapidly and to a greater extent than with lifestyle-based interventions.

This phenomenon is explained by metabolic and hormonal adaptations that promote weight regain, such as increased hunger signals or reduced energy expenditure. These changes may persist over time, highlighting the need for long-term maintenance strategies.

Weight loss: metabolic effect or calorie restriction?

The article highlights that these drugs can reduce caloric intake by 16% to 39%, which raises a clinically and ethically relevant debate: is the drug “fixing” metabolism, or is weight loss mainly driven by reduced food intake due to increased satiety or discomfort?

In this context, the authors point out the need for studies that account for factors such as diet and physical activity in order to determine the independent effect of the drug.

The key role of lifestyle

Clinical guidelines continue to recommend that obesity treatment should be based on a comprehensive lifestyle intervention, including a balanced hypocaloric diet, regular physical activity, and behavioural support.

Although these interventions achieve more modest weight loss, they provide additional benefits in overall health, quality of life, and management of comorbidities, and have proven to be cost-effective.

The article emphasizes that nutritional therapy should be integrated into treatment with these drugs to prevent long-term adverse effects and ensure patients’ nutritional status.

Beyond the drug: context matters

The authors stress that these medications are intended as a complement to a low-calorie diet and increased physical activity, and warn that their use outside a structured program may limit benefits and increase risks.

They also underline that obesity management cannot rely solely on pharmacological approaches, as social, environmental, and behavioural factors play a key role.

Open questions

The article concludes by raising several questions that still need to be addressed, such as the exact mechanisms behind weight loss, long-term safety, real-world effectiveness, and cost-effectiveness.