What Is Glucagon-Like Peptide-1 (GLP-1)?

Glucagon-like peptide-1 (GLP-1) is a naturally occurring incretin hormone that plays a central role in regulating blood sugar, appetite and digestion. Released by cells in the gut after eating, it stimulates insulin secretion, suppresses glucagon, slows gastric emptying and signals fullness to the brain. Understanding what GLP-1 is and how it works is increasingly important as GLP-1 receptor agonists such as semaglutide and tirzepatide become widely used in the UK for type 2 diabetes and weight management. This article explains the science, the available medicines, who may be suitable, and what side effects to watch for.

What is glucagon-like peptide-1 and what does it do in the body?

GLP-1 is a gut-derived incretin hormone that stimulates insulin release, suppresses glucagon, slows gastric emptying and signals satiety to the brain. Its natural half-life is one to two minutes before inactivation by DPP-4.

Glucagon-like peptide-1 (GLP-1) is a naturally occurring hormone produced primarily by L-cells in the distal small intestine and colon in response to eating, and it plays a central role in regulating blood sugar, appetite and digestion.^[1] It belongs to a family of incretin hormones, meaning it is released after a meal to help the body manage the rise in blood glucose that follows food intake. GLP-1 was first characterised in the 1980s and has since become one of the most studied targets in metabolic medicine.^[1]

In the body, GLP-1 acts on several organs simultaneously. It stimulates the pancreas to release insulin when blood glucose is elevated, suppresses the release of glucagon (a hormone that raises blood sugar), slows the rate at which the stomach empties its contents into the small intestine, and signals to the brain that the body has had enough to eat. These combined effects make GLP-1 a powerful regulator of both glucose metabolism and energy balance.

Natural GLP-1 is rapidly inactivated in the bloodstream by the enzyme dipeptidyl peptidase-4 (DPP-4), with a half-life of approximately one to two minutes, so its effects in healthy individuals are short-lived. This limitation prompted researchers to develop GLP-1 receptor agonists: medicines that mimic the action of GLP-1 but are engineered to resist rapid breakdown, allowing them to remain active for hours or even a full week depending on the formulation. Understanding how the natural hormone works is essential context for understanding how these medicines produce their clinical effects.

How does GLP-1 help control blood sugar and appetite?

GLP-1 stimulates insulin secretion only when blood glucose is elevated and suppresses glucagon, keeping post-meal glucose rises within a tighter range. It also acts on hypothalamic receptors to promote fullness and reduce caloric intake.

GLP-1 controls blood sugar primarily by stimulating insulin secretion from the pancreatic beta cells in a glucose-dependent manner, meaning it only triggers insulin release when blood glucose is actually elevated. This substantially reduces the risk of hypoglycaemia compared with some older diabetes medicines such as sulphonylureas or insulin, a property reflected in NICE guidance and BNF monographs for this medicine class. At the same time, GLP-1 suppresses glucagon from the alpha cells of the pancreas, preventing the liver from releasing stored glucose into the bloodstream unnecessarily. Together, these two mechanisms keep post-meal blood glucose rises within a tighter range.

Appetite regulation is equally important. GLP-1 receptors are present in the hypothalamus and other brain regions involved in hunger and satiety.^[1] When GLP-1 binds to these receptors, it promotes feelings of fullness and reduces the drive to eat. Gastric emptying is also slowed, so food remains in the stomach for longer, prolonging the sensation of fullness after a meal. Clinical trials supporting NICE appraisals of licensed GLP-1 receptor agonists have demonstrated meaningful reductions in caloric intake as a result of these combined central and peripheral effects.

It is worth noting that GLP-1 receptor agonists amplify these natural signals rather than creating entirely new ones. This is why their appetite-suppressing effects tend to feel more physiological than those of older weight-loss medicines. The glucose-dependent nature of their insulin-stimulating action is also a key safety advantage, as the risk of blood sugar falling dangerously low is considerably lower than with sulphonylureas or insulin when used alone, though the risk increases if GLP-1 receptor agonists are combined with those medicines.

Which GLP-1 medicines are available on the NHS?

NHS-available GLP-1 receptor agonists include semaglutide, liraglutide, dulaglutide and tirzepatide, subject to NICE recommendations and local ICB commissioning decisions for diabetes or weight management indications.

Several GLP-1 receptor agonists are currently available in the UK, though NHS access depends on the specific indication, local Integrated Care Board (ICB) commissioning decisions, and whether NICE has recommended the medicine for a given use. It is important to understand that NICE recommends medicines for NHS use but does not approve them; the MHRA grants marketing authorisations, and individual ICBs make local commissioning decisions.

For type 2 diabetes, options that have received NICE recommendations include:

• Semaglutide (Ozempic, weekly subcutaneous injection; and oral semaglutide Rybelsus, daily tablet)

• Liraglutide (Victoza, daily subcutaneous injection)

• Dulaglutide (Trulicity, weekly subcutaneous injection)

• Exenatide (Byetta, twice-daily injection; and Bydureon, weekly injection), patients and prescribers should confirm current availability with their pharmacy or ICB, as supply and market status for these presentations has changed over time

• Tirzepatide (Mounjaro, weekly subcutaneous injection), which acts on both GLP-1 and GIP receptors and is MHRA-authorised for both type 2 diabetes and chronic weight management^[6][14]

For chronic weight management specifically, NICE has recommended semaglutide 2.4 mg (Wegovy, weekly subcutaneous injection, with a higher 7.2 mg strength also MHRA-authorised) and tirzepatide (Mounjaro) for eligible adults. Liraglutide 3 mg (Saxenda) is also MHRA-authorised for weight management. Orforglipron (Foundayo) has received a UK marketing authorisation for chronic weight management; its NICE appraisal and NHS commissioning position should be confirmed with your prescriber or ICB.^[15] Oral semaglutide for weight management (Wegovy 25 mg tablets) received MHRA authorisation in June 2026 and is a distinct product from Rybelsus with a different licensed posology.^[10]

Bolt Pharmacy is a GPhC-registered UK online pharmacy offering online weight-management consultations, with prescriber review and pharmacist support, where a range of clinically appropriate options may be considered following a consultation. Availability on the NHS varies, and patients should discuss eligibility with their GP or specialist.

Who is suitable for GLP-1 receptor agonist treatment in the UK?

Suitability depends on indication, BMI, HbA1c, kidney function and cardiovascular risk, assessed by a prescriber. These medicines are not recommended in pregnancy, severe gastroparesis or with hypersensitivity to any component.

Suitability for GLP-1 receptor agonist treatment depends on the indication, the specific medicine, and individual clinical circumstances, and a prescriber must assess each person before treatment begins. For type 2 diabetes, NICE guidance (including NG28 and relevant technology appraisals) generally positions GLP-1 receptor agonists as an option when blood sugar remains inadequately controlled despite other medicines, or where weight management or cardiovascular risk reduction is a particular priority. Prescribers will consider factors such as HbA1c levels, body weight, kidney function and existing cardiovascular disease.

For weight management, NICE criteria for semaglutide (Wegovy) and tirzepatide (Mounjaro) specify a BMI threshold (typically 35 kg/m² or above, or 30 kg/m² or above with at least one weight-related comorbidity, with lower thresholds applying for certain ethnic groups as set out in the relevant NICE technology appraisals) alongside the requirement that the medicine is used as part of a specialist weight management service.^[12][13] Local ICB commissioning decisions affect whether these criteria translate into funded NHS prescriptions in a given area.

If GLP-1 receptor agonists are used alongside insulin or a sulphonylurea, the risk of hypoglycaemia increases and dose adjustments to those medicines may be needed; this should be discussed with a prescriber.

GLP-1 receptor agonists are not suitable for everyone. They are generally avoided or used with caution in:

• Pregnancy and breastfeeding: these medicines are not recommended during pregnancy or while breastfeeding, and women of childbearing potential should use effective contraception. For tirzepatide specifically, the UK SmPC advises using an additional non-oral contraceptive method for four weeks after starting and for four weeks after each dose increase, as the medicine may reduce the absorption of oral contraceptives by slowing gastric emptying.^[6][16] Patients planning a pregnancy should discuss appropriate washout intervals with their prescriber, as these differ between agents.

• Severe gastroparesis: GLP-1 receptor agonists are generally avoided in severe gastroparesis; cautions relating to other gastrointestinal conditions vary by product and should be confirmed against the relevant UK SmPC.

• Personal or family history of certain thyroid conditions: the UK SmPC for GLP-1 medicines advises counselling on symptoms, though the human relevance of rodent C-cell findings remains uncertain.

• Hypersensitivity to the active substance or any excipient

What side effects should you watch for with GLP-1 based treatments?

The most common side effects are gastrointestinal, including nausea, vomiting and diarrhoea, which typically improve with gradual dose escalation. Serious risks include acute pancreatitis, gallbladder disease and hypoglycaemia when combined with insulin or sulphonylureas.

The most commonly reported side effects of GLP-1 receptor agonists are gastrointestinal in nature, and these are well documented across the class. Nausea, vomiting, diarrhoea, constipation and abdominal discomfort are particularly common when starting treatment or after a dose increase, and they tend to improve over several weeks as the body adjusts. Starting at a low dose and increasing gradually, as recommended in the prescribing information for all medicines in this class, helps to minimise these effects.

Persistent vomiting or diarrhoea can lead to dehydration, which in some cases may affect kidney function. It is important to maintain adequate fluid intake and to contact your prescriber or GP promptly if you are unable to keep fluids down or if symptoms are prolonged.

More serious but less common effects to be aware of include:

• Acute pancreatitis: the UK SmPC notes that acute pancreatitis has been reported, including post-marketing reports of necrotising pancreatitis and reports with a fatal outcome. If you develop persistent, severe abdominal pain, particularly if it radiates to the back, stop the medicine and seek urgent medical assessment. Call 999 if the pain is severe and sudden.

• Gallbladder problems: including gallstones and cholecystitis, which have been reported, particularly with rapid weight loss

• Heart rate increase: a modest increase in resting heart rate has been observed with some medicines in this class

• Diabetic eye disease: in people with pre-existing pre-proliferative or proliferative diabetic retinopathy, rapid improvement in blood glucose control may be associated with transient worsening of eye disease; regular eye screening remains important^[19][20]

• Hypoglycaemia: when a GLP-1 receptor agonist is used alongside insulin or a sulphonylurea, the risk of low blood sugar is increased; your prescriber may adjust the doses of those medicines accordingly

If you experience an unexpected or concerning side effect, report it to your prescriber or pharmacist. Suspected adverse reactions to medicines can also be reported directly to the MHRA via the Yellow Card scheme at yellowcard.mhra.gov.uk. For non-urgent concerns, contact your GP; for urgent advice, call NHS 111.

As with all medicines, the balance of benefits and risks should be reviewed regularly with a healthcare professional.

Scientific References

1. The physiology of glucagon-like peptide 1. Holst JJ. Physiol Rev..
2. GLP-1 receptor agonists and DPP-4 inhibitors in the treatment of type 2 diabetes. Ahrén B..
3. Ozempic 0.5 mg solution for injection in pre-filled pen.
4. Semaglutide | Drugs – BNF – NICE.
5. Type 2 diabetes | Treatment summaries – BNF – NICE.
6. Tirzepatide | Drugs – BNF – NICE.
7. Summary of NICE guidance for GLP-1 receptor agonists and tirzepatide in adults (NG28 resource).
8. Type 2 diabetes in adults: choosing, reviewing and stopping medicines (NG28) – visual summary.
9. Semaglutide: a medicine to manage type 2 diabetes or treat obesity.
10. First GLP-1 tablet for weight loss approved in the UK (Wegovy 25 mg tablets).
11. Single-dose 7.2 mg semaglutide (Wegovy) pen approved to treat adult patients with obesity.
12. Tirzepatide for managing overweight and obesity (TA1026).
13. Semaglutide for managing overweight and obesity (TA875).
14. MHRA authorises diabetes drug Mounjaro (tirzepatide) for weight management and weight loss.
15. UK first in Europe to authorise orforglipron (Foundayo) for weight management and type 2 diabetes.
16. Women on 'skinny jabs' must use effective contraception – MHRA urges in latest guidance.
17. GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists: strengthened warnings on acute pancreatitis, including necrotising and fatal cases.
18. GLP-1 receptor agonists: reminder of the potential side effects and to be aware of the potential for misuse.
19. Glucagon-like Peptide 1 Receptor Agonist use and the risk of diabetic retinopathy. Hui BTK et al..
20. Beyond Glycemic Control: Ocular Effects of Glucagon-like Peptide-1 Receptor Agonists. Vision (Basel)..
21. NG242 Diabetic retinopathy: management and monitoring – evidence review C.
22. Effects of Liraglutide Compared With Placebo on Events of Acute Gallbladder or Biliary Disease in the LEADER Trial. Diabetes Care..
23. Pancreatic and Gallbladder Adverse Events Associated with Tirzepatide in Obesity Management: A Scoping Review. Diabetes Metab Syndr Obes..

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