GLP-1: what it is, how it works and why it is transforming obesity treatment

Introduction

The term GLP-1 has gone from being endocrinology jargon to appearing in headlines, adverts and everyday conversation. And yet few people outside medicine really understand what it means, how it works and why it has so radically transformed the treatment of obesity.

This guide explains everything you need to know about GLP-1 with scientific rigour but in plain language: from the natural hormone your own body produces to the latest generation of medicines based on that mechanism. Information reviewed by Dr David Céspedes, Medical Director of AiON.

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

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

It is made mainly in the L cells of the small intestine, specifically in the ileum and the colon. Production rises when you eat, especially when nutrients reach these areas of the gut. That is why it is known as an incretin hormone, that is, a gut hormone that responds to food intake.

Physiological functions of endogenous GLP-1

• It stimulates insulin release by the pancreas in response to the rise in blood glucose after meals.
• It suppresses glucagon secretion, the hormone that raises glucose levels.
• It slows gastric emptying, prolonging the feeling of fullness.
• It acts on brain receptors in the hypothalamus that regulate appetite and the sensation of hunger.
• It helps protect the pancreatic beta cells.

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

From hormone to medicine: GLP-1 receptor agonists

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

A GLP-1 receptor agonist is a medicine designed to activate the same cell receptors that the natural hormone activates. They are man-made molecules (modified peptides) that mimic the structure and function of GLP-1, but with a far longer duration of action than the endogenous hormone, which breaks down within minutes.

History and evolution of GLP-1 agonists

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

First generation (2005-2015)

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

Second generation (2018-2021)

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

Third generation (2022 onwards): the dual agonists

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

Fourth generation under investigation

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

Mechanisms of action: exactly how they work

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

In the pancreas

They stimulate insulin release only when glucose is elevated (a glucose-dependent mechanism). This lowers the risk of hypoglycaemia compared with other diabetes medicines. At the same time, they suppress glucagon release.

In the stomach and intestine

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

In the brain

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

In the cardiovascular system

Long-term clinical trials have shown a reduction in major adverse cardiovascular events (myocardial infarction, stroke, cardiovascular death) in patients with type 2 diabetes and high cardiovascular risk, an effect that would not depend on weight loss alone.

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 the Spanish National Health System subject to criteria.
• Trulicity (dulaglutide): weekly dose of 0.75 mg or 1.5 mg. Funded by the Spanish National Health System subject to criteria.
• Rybelsus (oral semaglutide): daily tablets. Funded by the Spanish National Health System subject to criteria.
• Victoza (liraglutide): daily dose. Funded by the Spanish National Health System subject to criteria.
• Mounjaro (tirzepatide): weekly dose of 2.5 to 15 mg. Not currently funded.

For obesity

• Wegovy (high-dose semaglutide): weekly dose up to 2.4 mg. Not funded by the Spanish National Health System.
• Saxenda (high-dose liraglutide): daily dose up to 3 mg. Not funded by the Spanish National Health System.

Clinical evidence: what the studies show

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

Weight loss

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

Type 2 diabetes control

Mean reductions in glycated haemoglobin (HbA1c) of between 1.5% and 2.4% in patients with type 2 diabetes, greater than with most oral diabetes medicines. The size of the effect depends on the starting HbA1c: the higher it is, the greater the fall. Source: the SUSTAIN (semaglutide) and SURPASS (tirzepatide) programmes.

Cardiovascular protection

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

Additional effects

Emerging data suggest benefits for non-alcoholic fatty liver disease, obstructive sleep apnoea, diabetic kidney disease and potentially brain health (research into Alzheimer's disease is ongoing).

Limitations and who is not a candidate

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

• A 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 substance.
• Active, unstabilised eating disorders.
• Advanced kidney or liver disease (requires specific assessment).
• Patients with a BMI below 27 and no specific comorbidities.

The near future: where the field is heading

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

• Triple agonists (GLP-1 + GIP + glucagon): retatrutide, at an advanced stage, shows losses of more than 24%.
• Second-generation oral formulations with better bioavailability.
• Combinations with amylin (CagriSema) or with other metabolic peptides.
• Research into non-metabolic applications: Alzheimer's disease, Parkinson's disease, addictions.
• Longer duration: monthly formulations in development.

Conclusion

GLP-1 receptor agonists are probably the most significant therapeutic advance in bariatric and metabolic medicine of recent decades. Their mechanism is elegant: to replicate and amplify a regulatory system your own body already uses.

These medicines are not, however, a universal solution or a consumer product. They are prescription-only medicines for important clinical reasons: they have contraindications, side effects that are manageable but real, they require careful dose titration and ongoing monitoring, and their effectiveness depends critically on being used within a comprehensive medical programme that includes full assessment, an appropriate nutrition plan and professional supervision.

Using hormonal appetite modulators requires specialist medical assessment

At Peso we combine the latest bariatric medicine with the clinical supervision needed to make the pharmacological approach safe and effective. Our medical team, supervised by Medical Director Dr David Céspedes, assesses your individual case and, if you are a candidate, designs your personalised medical protocol. If you are not a candidate, you pay nothing.

Find out if you are a candidate

Frequently asked questions

Are GLP-1 and Ozempic the same thing?

Not exactly. GLP-1 is a hormone that occurs naturally in 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, and Ozempic is one of the best known.

Which GLP-1 medicine is best for weight loss?

At present tirzepatide (Mounjaro/Zepbound), a dual GLP-1 and GIP agonist, shows the greatest average efficacy for weight loss in clinical trials. The right clinical choice, however, depends on the individual patient's profile. There is no medicine that is universally best.

Are GLP-1 medicines safe?

They are medicines with extensive safety evidence when used under appropriate medical supervision and in correctly selected patients. They do have side effects, mostly gastrointestinal and manageable, and some specific contraindications. That is why they require a medical prescription.

Do you regain weight after stopping GLP-1 treatment?

Studies show that after stopping treatment there is partial regain of the weight lost if lifestyle changes are not maintained. Obesity is a chronic condition, and drug treatment works while it is being taken. 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 prescription-only medicines. Selling them without a prescription is illegal. Any website offering them without a prescription is operating outside the legal framework and the product may be counterfeit.

Your next step

Understanding how GLP-1 medicines work is half the journey; the other half is knowing whether they make sense in your case, and that cannot be answered in an article. Medical weight-loss treatment is now available in Spain, with prior assessment, a prescription where appropriate from a registered doctor and ongoing follow-up by the medical team. You can check whether you are eligible in 30 seconds.

Legal notice

This content is for information and general education. It is in no way a substitute for professional medical advice, diagnosis or treatment. The medicines mentioned in this article are prescription-only medicines that can only be dispensed with an official prescription issued by an authorised healthcare professional. Always consult an endocrinologist before starting any weight-loss treatment.