GLP-1: what they are, how they work and why they are revolutionising obesity treatment

Reading time: 11 minutes. Last updated: April 2026. Reviewed by Dr. David Céspedes, Specialist in Preventive Medicine and Longevity.

Introduction

The word GLP-1 has gone from being a technical term used by endocrinologists to appearing in headlines, adverts and everyday conversations. And yet, few people outside the medical field really understand what it means, how it works and why it has revolutionised the treatment of obesity so radically.

This guide explains with scientific rigour but in clear language everything you need to know about GLP-1: from the natural hormone your own body produces to the latest-generation medicines based on that mechanism. Information reviewed by Dr. David Céspedes, a licensed endocrinologist specialised in preventive medicine and longevity.

The GLP-1 hormone: what it does in your body naturally

GLP-1 stands for Glucagon-Like Peptide 1. It is a hormone that your own organism produces naturally from birth.

It is mainly produced in the L cells of the small intestine, specifically in the ileum and colon. Its production increases when you eat, especially when nutrients reach these intestinal areas. This is why it is known as an incretin hormone, that is, an intestinal hormone that responds to food intake.

Physiological functions of endogenous GLP-1

• Stimulates insulin release by the pancreas in response to the rise in blood glucose after meals.
• Suppresses glucagon secretion, the hormone that raises glucose levels.
• Slows gastric emptying, prolonging the feeling of satiety.
• Acts on brain receptors in the hypothalamus that regulate appetite and the feeling of hunger.
• Contributes to the protection of pancreatic beta cells.

In healthy people, this system works with precision: you eat, GLP-1 is released, you regulate glucose, you feel satiety, you stop eating. In people with obesity or type 2 diabetes, this system may be altered, with a diminished GLP-1 response after meals.

From the hormone to the medicine: GLP-1 receptor agonists

If natural GLP-1 has all these positive effects on metabolism, a logical question arises: could we pharmacologically replicate those effects to treat diabetes and obesity? That was exactly the research line that began in the 1980s and culminated with the first generation of GLP-1 agonists.

A GLP-1 receptor agonist is a medicine designed to activate the same cellular receptors activated by the natural hormone. They are artificial molecules (modified peptides) that mimic the structure and function of GLP-1, but with much longer duration of action than the endogenous hormone, which degrades within minutes.

History and evolution of GLP-1 agonists

The development of GLP-1 agonists as a pharmacological class is a story of progressive refinement over two decades.

First generation (2005-2015)

• Exenatide (Byetta, Bydureon): first approved GLP-1 agonist, derived from the venom of the Gila monster. Daily or weekly administration.
• Liraglutide (Victoza, Saxenda): longer duration of action, daily administration. Saxenda was the first GLP-1 agonist approved specifically for obesity.
• Dulaglutide (Trulicity): weekly administration. Improvement in comfort.

Second generation (2018-2021)

• Injectable semaglutide (Ozempic, Wegovy): weekly administration, greater efficacy in weight loss. Ozempic authorised for type 2 diabetes; Wegovy specifically for obesity.
• Oral semaglutide (Rybelsus): first GLP-1 agonist in oral tablet form for type 2 diabetes.

Third generation (2022 onwards): dual agonists

• Tirzepatide (Mounjaro, Zepbound): first dual GLP-1 and GIP agonist. Greater clinical efficacy than any previous mono GLP-1 agonist. Mounjaro authorised for type 2 diabetes; Zepbound (not yet in the EU in 2026) for obesity.

Fourth generation under investigation

• Retatrutide: triple GLP-1, GIP and glucagon agonist, in advanced clinical trials. Preliminary results show weight losses above 24%.
• Second-generation oral formulations with better bioavailability.
• Combinations with amylin and other peptides.

Mechanisms of action: exactly how they act

Pharmacological GLP-1 agonists act on the same receptors as the natural hormone, but with much greater potency and duration. Their clinical effects are the result of activating GLP-1 receptors in multiple tissues.

In the pancreas

They stimulate the release of insulin only in the presence of elevated glucose (glucose-dependent mechanism). This reduces the risk of hypoglycaemia compared to other antidiabetics. Simultaneously, they suppress the release of glucagon.

In the stomach and intestine

They slow gastric emptying, which prolongs the feeling of fullness. This is one of the reasons why patients report early and prolonged satiety.

In the brain

They cross the blood-brain barrier and act on hypothalamic nuclei involved in appetite regulation. This is the mechanism that explains the reduction of food noise, the decrease in constant thinking about food that many patients describe as the most transformative effect of the treatment.

In the cardiovascular system

Long-term clinical trials have demonstrated reduction of major cardiovascular events (heart attack, stroke, cardiovascular death) in patients with type 2 diabetes and high cardiovascular risk, an effect that would not depend only on weight loss.

GLP-1 agonist medicines available in Spain

The following GLP-1 receptor agonists are authorised and marketed in Spain.

For type 2 diabetes

• Ozempic (injectable semaglutide): weekly doses of 0.25 mg, 0.5 mg and 1 mg. Funded by SNS with criteria.
• Trulicity (dulaglutide): weekly dose of 0.75 mg or 1.5 mg. Funded by SNS with criteria.
• Rybelsus (oral semaglutide): daily tablets. Funded by SNS with criteria.
• Victoza (liraglutide): daily dose. Funded by SNS with criteria.
• Mounjaro (tirzepatide): weekly dose 2.5 to 15 mg. Not currently funded.

For obesity

• Wegovy (semaglutide at high doses): weekly dose up to 2.4 mg. Not funded by SNS.
• Saxenda (liraglutide at high doses): daily dose up to 3 mg. Not funded by SNS.

Clinical evidence: what the studies say

GLP-1 agonists are probably the therapeutic class with the greatest amount of solid clinical evidence of the last decade. The main findings from large-scale trials include:

Weight loss

The STEP (semaglutide) and SURMOUNT (tirzepatide) trials show mean losses between 15% and 21% of initial body weight in patients with obesity, at 68-72 weeks of supervised treatment. These figures far triple what was achieved with previous generations.

Type 2 diabetes control

Mean reductions of glycated haemoglobin (HbA1c) between 1% and 2.5%, higher than most oral antidiabetics.

Cardiovascular protection

The LEADER, SUSTAIN-6, REWIND and SELECT trials show a significant reduction of major cardiovascular events in high-risk patients.

Additional effects

Emerging data suggest benefits on non-alcoholic fatty liver disease, obstructive sleep apnoea, diabetic kidney disease and potentially on brain health (active research in Alzheimer's).

Limitations and non-candidate profiles

GLP-1 agonists are not suitable for all patients. The most relevant limitations and contraindications include:

• Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 syndrome.
• Active acute or chronic pancreatitis.
• Pregnancy and breastfeeding.
• Known hypersensitivity to the active ingredient.
• Active eating disorders not stabilised.
• Advanced kidney or liver disease (requires specific evaluation).
• Patients with BMI below 27 without specific comorbidities.

The immediate future: where the field is going

The development of medicines based on GLP-1 and related mechanisms is far from over. The most promising research lines include:

• Triple agonists (GLP-1 + GIP + glucagon): retatrutide in advanced phase shows losses above 24%.
• Second-generation oral formulations with better bioavailability.
• Combinations with amylin (cagrisema) or with other metabolic peptides.
• Research in non-metabolic applications: Alzheimer's, Parkinson's, addictions.
• Duration extension: monthly formulations under development.

Conclusion

GLP-1 receptor agonists probably represent the most significant therapeutic advance in bariatric and metabolic medicine of the last decades. Their mechanism is elegant: replicating and amplifying a regulatory system that your own body already uses.

However, these medicines are not a universal solution nor consumer products. They are drugs subject to medical prescription for important clinical reasons: they have contraindications, manageable but real side effects, they require careful titration and continuous follow-up, and their efficacy critically depends on their being used within the framework of a comprehensive medical programme that includes complete evaluation, an adequate nutritional plan and professional supervision.

The use of hormonal appetite modulators requires specialised medical evaluation

At FitRX we integrate the latest-generation bariatric medicine with the clinical supervision necessary for the pharmacological approach to be safe and effective. Dr. David Céspedes, a licensed endocrinologist, evaluates your individual case and, if you are a candidate, designs your personalised medical protocol. If you are not a candidate, you pay nothing.

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Frequently asked questions

Is GLP-1 the same as Ozempic?

Not exactly. GLP-1 is a natural hormone of the human body. Ozempic is a medicine (semaglutide) that acts on the same receptors as that hormone, which is why it is called a "GLP-1 receptor agonist". There are several GLP-1 agonist medicines on the market, Ozempic being one of the best known.

Which is the best GLP-1 medicine for losing weight?

Currently tirzepatide (Mounjaro/Zepbound), which is a dual GLP-1 and GIP agonist, shows greater average efficacy in weight loss in clinical trials. However, the right clinical choice depends on the individual profile of the patient. There is no universally better medicine.

Are GLP-1 medicines safe?

They are medicines with broad evidence of safety when used under adequate medical supervision and in properly selected patients. They have side effects, mostly gastrointestinal and manageable, and some specific contraindications. That is why they require medical prescription.

Is weight regained when stopping GLP-1 medicines?

Studies show that after suspending treatment there is partial regain of lost weight if lifestyle changes are not maintained. Obesity is a chronic condition, and pharmacological treatment acts while it is administered. That is why long-term medical follow-up is key.

Are GLP-1 medicines sold without a prescription?

No. All GLP-1 agonist medicines available in Spain are drugs subject to mandatory medical prescription. Their sale without a prescription is illegal. Any website that offers them without a prescription operates outside the legal framework and the product may be counterfeit.

Legal notice

This content is informative and educational. It does not replace professional medical advice, diagnosis or treatment under any circumstances. The medicines mentioned in this article are drugs subject to medical prescription whose dispensation requires an official prescription issued by an authorised healthcare professional. Always consult an endocrinologist before starting any treatment for weight loss.