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

GLP-1 receptor agonists are a group of medicines. They copy a natural hormone called glucagon-like peptide-1 (GLP-1). Your gut releases this hormone after you eat.

The role of GLP-1 in the body:

When you eat, cells in your small intestine release GLP-1 into the blood. This hormone does several useful things:

• It triggers insulin release from the pancreas, but only when your blood sugar is raised (this is called a glucose-dependent effect)
• It lowers glucagon, a hormone that raises blood sugar by telling the liver to make more glucose
• It slows down how fast your stomach empties, so you feel full for longer after meals
• It acts on the brain to curb appetite and reduce how much you eat

Natural GLP-1 does not last long. An enzyme called dipeptidyl peptidase-4 (DPP-4) breaks it down within minutes. GLP-1 receptor agonists are changed versions of the hormone.

They resist this breakdown, so they stay active for much longer.

Why they work so well:

These medicines keep the GLP-1 receptor switched on for a long time. This gives a much stronger effect than your body's own GLP-1 ever could.

That is why they have such a powerful effect on blood sugar, appetite and body weight.

NICE and the BNF list GLP-1 receptor agonists as a key treatment for type 2 diabetes. More recently, they are also used for long-term weight management.

Several GLP-1 receptor agonists are licensed and available in the UK. Each one has its own features and approved uses.

Semaglutide:

• [Ozempic](/en-gb/ozempic/) (injection, 0.25 mg to 2 mg weekly): licensed for type 2 diabetes
• [Wegovy](/en-gb/wegovy/) (injection, 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-gb/mounjaro/) (injection, 2.5 mg to 15 mg weekly): a dual GIP/GLP-1 agonist licensed for type 2 diabetes and weight management

Liraglutide:

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

Dulaglutide:

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

Exenatide:

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

Lixisenatide:

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

Doctors do not prescribe all of these often. Semaglutide and tirzepatide are the most widely used at the moment. They work better than the others and have simple dosing schedules.

GLP-1 receptor agonists differ a lot. They vary in strength, how often you take them and how much trial evidence supports them.

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): about 5% body weight
• Exenatide weekly: about 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 tend to cause similar gut side effects. The most common are nausea, diarrhoea and vomiting. These are usually worst while you build up the dose, and they ease with time.

The newer medicines, semaglutide and tirzepatide, raise the dose more slowly. This schedule is designed to keep these effects to a minimum.

GLP-1 receptor agonists do more than control blood sugar and aid weight loss. They have also shown clear benefits for the heart and kidneys.

Cardiovascular outcomes:

• Semaglutide: in the SELECT trial, semaglutide 2.4 mg cut the risk of major adverse cardiovascular events (MACE) by 20%. This was in overweight and obese adults who already had heart disease, whether or not they had diabetes
• Liraglutide: the LEADER trial showed a 13% drop in MACE in people with type 2 diabetes
• Dulaglutide: the REWIND trial showed a 12% drop in MACE
• Tirzepatide: heart outcome data from the SURPASS-CVOT trial are due to report in the coming years

Kidney protection:

The FLOW trial showed that semaglutide 1 mg slowed chronic kidney disease in people with type 2 diabetes. This led to a new approved use for GLP-1 agonists.

Metabolic syndrome improvements:

• Lower systolic blood pressure (usually 2 to 6 mmHg)
• Better lipid (blood fat) levels, especially triglycerides
• Less fat in the liver (this matters for non-alcoholic fatty liver disease)
• Lower levels of inflammatory markers

NICE now advises using GLP-1 agonists sooner in the type 2 diabetes treatment pathway. This is mainly for people who already have heart disease or a high risk of it.

These wider benefits are the reason for the change.

Has your prescriber suggested a GLP-1 receptor agonist? Here is what usually happens.

Before starting:

• Your prescriber will check your medical history, your current medicines and anything that might rule the treatment out
• You will usually have baseline blood tests, such as HbA1c and tests of kidney and liver function
• Your prescriber will talk you through the likely benefits and the possible side effects
• For weight management, you will usually need to be under the care of a specialist service

Starting treatment:

• All GLP-1 agonists start at a low dose, then go up slowly step by step
• If you use an injection pen, a nurse or pharmacist will show you how
• You inject these medicines just under the skin, into the abdomen, thigh or upper arm

The first few weeks:

• Mild nausea and a smaller appetite are the most common early effects
• Eat smaller meals and avoid fatty foods to ease gut symptoms
• Drink plenty of fluids, especially if you have diarrhoea or vomiting
• Tell your prescriber about any severe or lasting symptoms

Ongoing monitoring:

• Your HbA1c is usually checked every 3 to 6 months
• Your weight is recorded at each appointment
• For weight management, NICE says to review whether you should keep going. You should reach at least 5% weight loss by a set point in time
• You usually need treatment long term. Many people regain weight after they stop a GLP-1 agonist