GLP-1 medications explained: how they work and which is right for you

GLP-1 receptor agonists are a group of medicines that work by mimicking a natural hormone called glucagon-like peptide-1 (GLP-1), which is released by the gut after eating.

The role of GLP-1 in the body:

After you eat, cells in the small intestine release GLP-1 into the bloodstream. This hormone has several important effects:

• Stimulates insulin release from the pancreas in a glucose-dependent manner (only when blood sugar is raised)
• Suppresses glucagon, a hormone that raises blood sugar by stimulating liver glucose production
• Slows gastric emptying, prolonging the feeling of fullness after meals
• Acts on the brain to reduce appetite and food intake

Natural GLP-1 is broken down within minutes by an enzyme called dipeptidyl peptidase-4 (DPP-4).

GLP-1 receptor agonists are modified versions of this hormone that resist breakdown and remain active for much longer.

Why they are so effective:

By producing sustained GLP-1 receptor activation, these medicines achieve effects that far exceed those of the body's natural GLP-1 response.

This explains their potent effects on blood sugar control, appetite and body weight.

NICE and the BNF classify GLP-1 receptor agonists as a key treatment option for type 2 diabetes and, more recently, for chronic weight management.

Several GLP-1 receptor agonists are licensed and available in the UK. Each has distinct properties and approved indications.

Semaglutide:

• [Ozempic](/en/ozempic/) (injectable, 0.25 mg to 2 mg weekly): licensed for type 2 diabetes
• [Wegovy](/en/wegovy/) (injectable, 2.4 mg weekly): licensed for weight management
• Rybelsus (oral tablets, 3 mg to 14 mg daily): licensed for type 2 diabetes only

Tirzepatide:

• [Mounjaro](/en/mounjaro/) (injectable, 2.5 mg to 15 mg weekly): a dual GIP/GLP-1 agonist licensed for type 2 diabetes and weight management

Liraglutide:

• Victoza (injectable, 1.8 mg daily): licensed for type 2 diabetes
• Saxenda (injectable, 3 mg daily): licensed for weight management

Dulaglutide:

• Trulicity (injectable, 0.75 mg to 4.5 mg weekly): licensed for type 2 diabetes

Exenatide:

• Byetta (injectable, twice daily): licensed for type 2 diabetes
• Bydureon (injectable, 2 mg weekly): licensed for type 2 diabetes

Lixisenatide:

• Lyxumia (injectable, 20 mcg daily): licensed for type 2 diabetes

Not all of these are commonly prescribed. Semaglutide and tirzepatide are currently the most widely used due to their superior efficacy and convenient dosing schedules.

The GLP-1 receptor agonists vary considerably in their potency, dosing frequency and clinical evidence base.

Weight loss comparison (approximate averages):

• Tirzepatide 15 mg (Mounjaro): 22.5% body weight at 72 weeks
• Semaglutide 2.4 mg (Wegovy): 14.9% body weight at 68 weeks
• Liraglutide 3 mg (Saxenda): 8% body weight at 56 weeks
• Dulaglutide 4.5 mg (Trulicity): approximately 5% body weight
• Exenatide weekly: approximately 2 to 3% body weight

HbA1c reduction (approximate):

• Tirzepatide: up to 2.4 percentage points
• Semaglutide injectable: up to 1.8 percentage points
• Semaglutide oral: up to 1.5 percentage points
• Liraglutide: up to 1.3 percentage points
• Dulaglutide: up to 1.6 percentage points

Dosing frequency:

• Once weekly: semaglutide (injectable), tirzepatide, dulaglutide, exenatide extended-release
• Once daily: liraglutide, oral semaglutide, lixisenatide
• Twice daily: exenatide immediate-release

Side effect profile:

All GLP-1 agonists share a common gastrointestinal side effect profile. Nausea, diarrhoea and vomiting are the most reported. These are generally worst during dose escalation and improve with time.

The newer agents (semaglutide, tirzepatide) have refined titration schedules designed to minimise these effects.

Beyond blood sugar control and weight loss, GLP-1 receptor agonists have demonstrated important benefits for heart and kidney health.

Cardiovascular outcomes:

• Semaglutide: the SELECT trial showed that semaglutide 2.4 mg reduced the risk of major adverse cardiovascular events (MACE) by 20% in overweight and obese adults with established cardiovascular disease, regardless of diabetes status
• Liraglutide: the LEADER trial demonstrated a 13% reduction in MACE in patients with type 2 diabetes
• Dulaglutide: the REWIND trial showed a 12% reduction in MACE
• Tirzepatide: cardiovascular outcome data from the SURPASS-CVOT trial are expected to report in the coming years

Kidney protection:

The FLOW trial demonstrated that semaglutide 1 mg significantly reduced the progression of chronic kidney disease in patients with type 2 diabetes, marking a new indication for GLP-1 agonists.

Metabolic syndrome improvements:

• Reductions in systolic blood pressure (typically 2 to 6 mmHg)
• Improvements in lipid profile, particularly triglycerides
• Reductions in liver fat content (relevant for non-alcoholic fatty liver disease)
• Improvements in inflammatory markers

NICE now recommends considering GLP-1 agonists earlier in the type 2 diabetes treatment pathway, particularly for patients with established cardiovascular disease or high cardiovascular risk, reflecting these broader benefits.

If your prescriber recommends a GLP-1 receptor agonist, here is what the process typically involves.

Before starting:

• Your prescriber will review your medical history, current medicines and any contraindications
• Baseline blood tests (HbA1c, renal function, liver function) are usually checked
• You will be counselled on the expected benefits and potential side effects
• For weight management, you will typically need to be engaged with a specialist service

Starting treatment:

• All GLP-1 agonists are started at a low dose and titrated upwards gradually
• You will be shown how to use the injection pen (if applicable) by a nurse or pharmacist
• Injectable GLP-1 agonists are given subcutaneously into the abdomen, thigh or upper arm

The first few weeks:

• Mild nausea and reduced appetite are the most common early effects
• Eat smaller meals and avoid fatty foods to minimise gastrointestinal symptoms
• Stay well hydrated, especially if experiencing diarrhoea or vomiting
• Report any severe or persistent symptoms to your prescriber

Ongoing monitoring:

• HbA1c is typically checked every 3 to 6 months
• Weight is recorded at each appointment
• For weight management, NICE recommends reviewing whether treatment should continue based on achieving a minimum 5% weight loss by a defined timepoint
• Long-term treatment is usually needed, as weight regain is common after stopping GLP-1 agonists