GIP and GLP-1: How They Work and UK Treatments

GIP and GLP-1 are gut-derived incretin hormones that regulate blood glucose, appetite and energy balance after eating. Interest in these hormones has grown considerably following the development of medicines that mimic or enhance their effects, including the first dual GIP and GLP-1 receptor agonist, tirzepatide (Mounjaro), now authorised in the UK. This article explains how GIP and GLP-1 work, which medicines target their receptors, how NHS access is determined, and what side effects patients and clinicians should monitor when using these treatments.

What are GIP and GLP-1 and what do they do in the body?

GIP and GLP-1 are incretin hormones released from the gut after eating that stimulate insulin secretion, suppress glucagon, slow gastric emptying and reduce appetite. In type 2 diabetes, this incretin effect is often diminished, contributing to poor blood glucose control.

GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) are naturally occurring hormones called incretins, released from the gut in response to eating. Both hormones play a central role in regulating blood glucose, appetite and energy balance, though they act through distinct but complementary pathways.

GLP-1 is secreted primarily from L-cells in the small intestine and colon.^[1][4] Once released, it stimulates insulin secretion from the pancreas in a glucose-dependent manner, meaning it only prompts insulin release when blood glucose is elevated, which reduces the risk of hypoglycaemia. GLP-1 also suppresses glucagon (a hormone that raises blood glucose), slows gastric emptying, and acts on appetite-regulating centres in the brain to reduce hunger and promote a feeling of fullness.

GIP is secreted from K-cells in the upper small intestine and similarly enhances insulin secretion after meals.^[2][3] It also plays a role in fat metabolism and may support the body's response to GLP-1 when both receptors are activated together, based on mechanistic and early clinical data. In people with type 2 diabetes, the incretin effect is often diminished, meaning these hormones do not work as effectively as they should, contributing to poor blood glucose control.^[5][6]

Understanding how GIP and GLP-1 work together has driven significant advances in the development of medicines that mimic or enhance their effects. Clinical trial data, including the SURPASS programme and conclusions reached by NICE, suggest that activating both receptors simultaneously may produce meaningful improvements in blood glucose control and body weight, though the magnitude of benefit varies by comparator and patient population.

Which medicines target GIP and GLP-1 receptors in the UK?

Tirzepatide (Mounjaro) is the only dual GIP and GLP-1 receptor agonist authorised in the UK; several GLP-1 receptor agonists, including semaglutide and liraglutide, are also available. All require a prescription and appropriate clinical supervision.

Several medicines targeting GLP-1 receptors are authorised in the UK, and one dual GIP and GLP-1 receptor agonist is now also available. These treatments differ in how many receptors they activate, their licensed indications, and how they are administered.

GLP-1 receptor agonists authorised in the UK include:

• Semaglutide, available as Ozempic (for type 2 diabetes) and Wegovy (for chronic weight management). Wegovy is available as a subcutaneous injection; the standard maintenance dose is 2.4 mg weekly, and the MHRA has also authorised a higher-strength 7.2 mg presentation. An oral semaglutide tablet for weight management, Wegovy 25 mg tablets, received MHRA authorisation in June 2026.^[10]

• Liraglutide, available as Victoza (type 2 diabetes) and Saxenda (chronic weight management), administered as a daily subcutaneous injection.

• Dulaglutide (Trulicity) and exenatide (Byetta, Bydureon) are also authorised for type 2 diabetes. Patients should confirm current availability of specific presentations with their pharmacist or prescriber, as supply status can change.

• Orforglipron (Foundayo) is an oral GLP-1 receptor agonist that has received a UK licence for weight management.^[11] Patients should discuss eligibility with their prescriber.

Dual GIP and GLP-1 receptor agonist:

• Tirzepatide (Mounjaro) is the first dual GIP and GLP-1 receptor agonist to receive MHRA authorisation in the UK. It is licensed both for the management of type 2 diabetes and for chronic weight management in adults. Mounjaro is administered once weekly using a multiple-dose KwikPen, with each pen containing four weekly doses.^[14][15] Bolt Pharmacy is a GPhC-registered UK online pharmacy offering online weight-management consultations, with prescriber review and pharmacist support, where tirzepatide is one option a prescriber may consider where it is clinically appropriate.

All of these medicines require a prescription and should only be used under appropriate clinical supervision.

Are dual GIP and GLP-1 receptor agonists available on the NHS?

Tirzepatide is available on the NHS for eligible patients under NICE guidance, but access depends on local ICB commissioning and a phased rollout through specialist weight management services. Patients who do not qualify may access it via private prescribing after clinical assessment.

Tirzepatide (Mounjaro) is available on the NHS for eligible patients, but access depends on the specific indication and local commissioning decisions made by Integrated Care Boards (ICBs). NICE recommends tirzepatide for certain uses, but NHS availability does not follow automatically from a NICE technology appraisal, and local ICBs determine how and when treatments are commissioned in their area.

For type 2 diabetes, NICE has issued guidance on tirzepatide as an add-on treatment option for adults who meet specific clinical criteria, including inadequate glycaemic control on existing therapy. For weight management, NICE technology appraisal TA1026 recommends tirzepatide as an option for chronic weight management in adults with obesity or overweight alongside at least one weight-related comorbidity, subject to defined BMI thresholds and other eligibility criteria.^[17][18] NHS England has outlined a phased rollout through specialist weight management services, meaning not all eligible patients will have immediate access through their local NHS service.^[19]

For patients who do not meet NHS criteria, or who are waiting for NHS access, tirzepatide may be available through private prescribing routes following an appropriate clinical assessment. It is important to distinguish between NHS prescription charges and private costs. In England, the standard NHS prescription charge applies per item for NHS-funded prescriptions, and a prepayment certificate may reduce costs for those on multiple regular medicines. NHS prescription charges do not apply in Wales, Scotland or Northern Ireland. Private prescription costs are entirely separate and vary by provider.

Patients interested in NHS access should speak to their GP or diabetes or weight management specialist, who can advise on local eligibility and referral pathways.

What side effects should you watch for with these treatments?

Gastrointestinal effects such as nausea, vomiting and diarrhoea are the most common side effects and usually improve over time. Pancreatitis is a rare but serious risk; persistent severe abdominal pain warrants stopping the medicine and seeking urgent medical advice.

GIP and GLP-1 receptor agonists share a broadly similar side effect profile, with gastrointestinal effects being the most commonly reported. Being aware of these effects, and knowing when to seek advice, supports safe use of these medicines.

Common side effects include:

• Nausea, vomiting, diarrhoea and constipation, particularly when starting treatment or after a dose increase

• Reduced appetite and indigestion

• Injection site reactions such as redness, bruising or discomfort

These effects are usually mild to moderate and tend to improve over time. Dose escalation schedules are designed to minimise them by allowing the body to adjust gradually. If vomiting or diarrhoea are severe or persistent, it is important to maintain fluid intake; seek medical advice promptly if you are unable to keep fluids down, as dehydration can place strain on the kidneys.

Less common but important effects to be aware of:

• Pancreatitis: Acute pancreatitis has been reported with GLP-1 and dual receptor agonists, including post-marketing reports of necrotising pancreatitis and cases with a fatal outcome.^[20] If you develop persistent, severe abdominal pain that may radiate to the back, stop the medicine and contact your GP promptly or call NHS 111 for urgent advice.

• Gallbladder problems: Cholelithiasis (gallstones) and cholecystitis have been reported, particularly with rapid weight loss.

• Heart rate: A modest increase in resting heart rate has been observed with some agents in this class.

• Diabetic eye disease: In people with pre-existing diabetic retinopathy, particularly pre-proliferative or proliferative disease, rapid improvement in blood glucose control may be associated with transient worsening. Those with known diabetic eye disease should discuss this with their clinician before starting treatment.

• Hypoglycaemia: When these medicines are used alongside insulin or a sulfonylurea, the risk of hypoglycaemia (low blood glucose) is increased.^[24][25] Your prescriber may need to adjust the doses of those medicines and advise on blood glucose monitoring.

Pregnancy, breastfeeding and contraception: These medicines are not recommended during pregnancy. If you are pregnant, planning a pregnancy, or think you may be pregnant, stop the medicine and speak to your GP or prescriber promptly. Effective contraception is advisable for women of childbearing potential while using these treatments. Use during breastfeeding is generally not recommended; discuss the risks and benefits with your clinician.

Suspected side effects from any medicine can be reported to the MHRA via the Yellow Card scheme at yellowcard.mhra.gov.uk. If you experience signs of a serious allergic reaction, such as difficulty breathing or significant facial swelling, call 999 immediately.

Scientific References

1. The physiology of glucagon-like peptide 1 (Holst JJ, Physiological Reviews, 2007).
2. Cardiovascular biology of the GIP receptor (Peptides, 2019).
3. Intestinal CART is a regulator of GIP and GLP-1 secretion and expression (Molecular and Cellular Endocrinology, 2018).
4. Distribution of K and L cells in the feline intestinal tract (Domestic Animal Endocrinology, 2013).
5. The incretin effect in healthy individuals and those with type 2 diabetes (Nauck MA et al., The Lancet Diabetes & Endocrinology, 2016).
6. Glucagon-Like Peptide-1 Agonists and Blood Pressure Regulation: Molecular Mechanisms and Cardiovascular Implications (Pharmacology Research & Perspectives, 2025).
7. Medicines regulator approves up to 7.2 mg dose of semaglutide/Wegovy for patients with obesity only.
8. Single-dose 7.2 mg semaglutide (Wegovy) pen approved to treat adult patients with obesity.
9. Wegovy Patient Information Leaflet (semaglutide) — EMC.
10. First GLP-1 tablet for weight loss approved in the UK (Wegovy 25 mg tablets, semaglutide).
11. UK first in Europe to authorise orforglipron (Foundayo) for weight management and type 2 diabetes.
12. MHRA authorises diabetes drug Mounjaro (tirzepatide) for weight management and weight loss.
13. Tirzepatide: a medicine to manage type 2 diabetes and weight — NHS.UK.
14. Four-dose Mounjaro KwikPen approved by MHRA for diabetes and weight management.
15. Mounjaro (tirzepatide) — EMA Product Information.
16. Mounjaro 2.5 mg KwikPen Patient Information Leaflet — EMC.
17. Tirzepatide for managing overweight and obesity (TA1026).
18. Tirzepatide for managing overweight and obesity — TA1026 Recommendations chapter.
19. NICE describes how weight loss drug tirzepatide will be rolled out — NICE News.
20. GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists: strengthened warnings on acute pancreatitis, including necrotising and fatal cases.
21. Association of Glucagon-Like Peptide-1 Receptor Agonist Use With Risk of Gallbladder and Biliary Diseases (He L et al., JAMA Internal Medicine, 2022).
22. Safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes and obesity: a systematic review and meta-analysis (Frontiers in Endocrinology, 2023).
23. NG242 Diabetic retinopathy: management and monitoring — effectiveness of intensive treatments to lower blood glucose levels.
24. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4) (The Lancet, 2021).
25. Tirzepatide — BNF/NICE.

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