Incretin hormones, particularly glucagon-like peptide-1 (GLP-1), play a vital role in regulating appetite and promoting feelings of fullness after eating. These naturally occurring hormones, produced in the gut, not only help control blood glucose levels but also influence how satisfied you feel during and after meals. Incretin-based medications, including GLP-1 receptor agonists such as semaglutide and liraglutide, mimic these natural effects and are increasingly used to manage type 2 diabetes and support weight loss. Understanding how incretins make you feel full can help patients and healthcare professionals optimise treatment outcomes whilst managing potential side effects.

What Are Incretins and How Do They Work?

Incretins are naturally occurring hormones produced in the gastrointestinal tract that play a crucial role in regulating blood glucose levels after eating. The two primary incretin hormones are glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). GLP-1 is secreted predominantly by L-cells in the distal ileum and colon, whilst GIP is released by K-cells in the duodenum and proximal jejunum. These hormones are released in response to food intake, particularly carbohydrates and fats.

The mechanism of action of incretins involves several coordinated processes. When food enters the digestive system, incretin hormones stimulate the pancreas to release insulin in a glucose-dependent manner—meaning insulin secretion only occurs when blood glucose levels are elevated. This physiological response helps prevent hypoglycaemia, a significant advantage over some other diabetes treatments. Additionally, GLP-1 suppresses the release of glucagon, a hormone that raises blood glucose levels, further contributing to glycaemic control.

Beyond their effects on insulin and glucagon, incretins influence gastric emptying by slowing the rate at which food leaves the stomach and enters the small intestine. This delayed gastric emptying contributes to more gradual glucose absorption and helps moderate post-meal blood sugar spikes. It is important to note that with long-acting GLP-1 receptor agonists, the gastric-emptying effect may diminish over time (tachyphylaxis), though other beneficial effects persist. Incretins also act on appetite-regulating centres in the brain, particularly the hypothalamus, where they promote feelings of satiety and reduce hunger signals.

In healthy individuals, incretin hormones are rapidly broken down by an enzyme called dipeptidyl peptidase-4 (DPP-4), which limits their duration of action. Understanding this natural degradation process has been fundamental to developing incretin-based medications that either resist breakdown or inhibit the DPP-4 enzyme, thereby prolonging the beneficial effects of these hormones in managing type 2 diabetes and, increasingly, obesity. (NICE NG28; MHRA/EMC SmPCs for semaglutide and liraglutide; EMA EPAR for semaglutide)

How Incretin Medications Affect Appetite and Satiety

Incretin-based medications work by mimicking or enhancing the natural effects of incretin hormones, and one of their most notable effects is the promotion of satiety—the feeling of fullness after eating. GLP-1 receptor agonists, in particular, have demonstrated significant appetite-suppressing properties that extend beyond their glucose-lowering effects. These medications bind to GLP-1 receptors in multiple locations throughout the body, including the brain's appetite control centres.

The satiety effect occurs through several interconnected mechanisms. Firstly, GLP-1 receptor agonists slow gastric emptying, meaning food remains in the stomach for longer periods. This mechanical distension of the stomach contributes to prolonged feelings of fullness and reduces the desire to eat. With long-acting GLP-1 receptor agonists, the gastric-emptying effect may lessen over time, though appetite suppression and other metabolic benefits typically persist. Secondly, these medications act directly on the central nervous system, particularly the hypothalamus and brainstem, where they modulate appetite-regulating pathways and reduce food-seeking behaviour.

Clinical studies have consistently demonstrated that patients taking GLP-1 receptor agonists experience reduced energy intake. Trials show measurable reductions in caloric consumption, though individual responses vary considerably. Patients often report feeling satisfied with smaller portion sizes and experiencing reduced hunger between meals. This effect appears to be dose-dependent, with higher doses generally producing more pronounced appetite suppression. The reduction in appetite typically begins within the first few weeks of treatment.

It is important to note that whilst the satiety effect can be beneficial for weight management, some patients may find the reduced appetite uncomfortable, particularly if it leads to nausea or difficulty consuming adequate nutrition. The appetite-suppressing effects are generally most pronounced during the initial titration period and may moderate somewhat over time, though sustained reductions in hunger and food intake typically persist throughout treatment. GLP-1 receptor agonists are not recommended for use in patients with severe gastrointestinal disease, including gastroparesis. Healthcare professionals should monitor nutritional adequacy, particularly in patients experiencing significant appetite suppression. (NICE TA875; EMA EPAR for semaglutide [Wegovy]; MHRA/EMC SmPCs for liraglutide and semaglutide)

Common Incretin Drugs Used in the UK

Several incretin-based medications are currently licensed and available through the NHS in the UK, falling into two main categories: GLP-1 receptor agonists (including dual GIP/GLP-1 receptor agonists) and DPP-4 inhibitors. These medications differ in their mechanisms, administration routes, and clinical applications.

GLP-1 receptor agonists available in the UK include:

• Semaglutide (Ozempic®, Wegovy®, Rybelsus®) – available as once-weekly subcutaneous injection or daily oral tablet. Wegovy® is specifically licensed for weight management in adults with a BMI ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidities, used within a specialist weight-management service.

• Dulaglutide (Trulicity®) – administered as a once-weekly subcutaneous injection, often preferred for its convenient pre-filled pen device.

• Liraglutide (Victoza®, Saxenda®) – given as a once-daily subcutaneous injection. Saxenda® is licensed for weight management at higher doses than Victoza®, with similar BMI eligibility criteria to Wegovy®.

• Exenatide (Bydureon®) – available as a once-weekly formulation. (Note: the twice-daily immediate-release formulation [Byetta®] may no longer be widely available in the UK; prescribers should verify current supply.)

• Tirzepatide (Mounjaro®) – a dual GIP/GLP-1 receptor agonist administered as a once-weekly subcutaneous injection, licensed for type 2 diabetes. (A separate weight-management indication may be authorised under a different brand name; prescribers should consult current NICE guidance and MHRA licensing.)

According to NICE NG28, GLP-1 receptor agonists are recommended for type 2 diabetes when metformin and other oral medications have not achieved adequate glycaemic control, or as an alternative to insulin therapy in appropriate patients. They may also be considered earlier in treatment pathways for specific patient groups. For weight management, NICE TA875 (semaglutide) and NICE TA664 (liraglutide) recommend these medications only within specialist weight-management services, after dietary, exercise, and behavioural interventions have been attempted, and with defined stopping rules (e.g., discontinue if <5% weight loss at 6 months for Saxenda®, or <5% at 6 months for Wegovy®).

DPP-4 inhibitors represent an alternative incretin-based approach and include:

• Sitagliptin (Januvia®)

• Linagliptin (Trajenta®)

• Saxagliptin (Onglyza®)

• Alogliptin (Vipidia®)

• Vildagliptin (Galvus®)

These oral medications work by preventing the breakdown of natural incretins rather than directly mimicking them. Whilst DPP-4 inhibitors improve glycaemic control, they produce less pronounced effects on appetite and weight compared to GLP-1 receptor agonists. They are generally weight-neutral and do not typically cause the significant satiety effects associated with GLP-1 receptor agonists. NICE NG28 recommends DPP-4 inhibitors as add-on therapy in type 2 diabetes management, or as an alternative first-line option if metformin is contraindicated or not tolerated. DPP-4 inhibitors should not be used in combination with GLP-1 receptor agonists. (NICE NG28; NICE TA875; NICE TA664; NICE Technology Appraisal for tirzepatide; MHRA/EMC SmPCs; NHS medicines pages)

Side Effects and What to Expect When Taking Incretins

Incretin medications are generally well-tolerated, but patients should be aware of potential side effects, particularly those related to the gastrointestinal system. Understanding what to expect can help patients manage symptoms and maintain treatment adherence.

Common gastrointestinal side effects include:

• Nausea – the most frequently reported side effect, particularly with GLP-1 receptor agonists. This typically occurs during treatment initiation or dose escalation and often improves within 2–4 weeks as the body adjusts.

• Vomiting and diarrhoea – these symptoms usually diminish over time but can be troublesome initially.

• Constipation – may occur due to slowed gastric emptying.

• Abdominal discomfort or bloating – related to delayed gastric emptying.

To minimise gastrointestinal side effects, healthcare professionals typically employ a gradual dose titration strategy, starting with lower doses and slowly increasing over several weeks. Patients can also help manage symptoms by eating smaller, more frequent meals, avoiding high-fat foods, and staying well-hydrated.

Less common but important side effects include:

• Hypoglycaemia – whilst incretin medications alone rarely cause low blood sugar, the risk increases when combined with insulin or sulphonylureas. If you are taking insulin and starting a GLP-1 receptor agonist, your insulin dose may need to be reduced gradually under medical supervision. The MHRA advises that insulin doses should not be reduced rapidly when initiating a GLP-1 receptor agonist, as this may increase the risk of diabetic ketoacidosis (DKA). Patients should be educated about recognising and managing hypoglycaemia.

• Injection site reactions – mild redness, itching, or swelling may occur with subcutaneous formulations.

• Acute gallbladder disease – GLP-1 receptor agonists are associated with an increased risk of gallstones (cholelithiasis) and gallbladder inflammation (cholecystitis). Seek medical attention if you experience severe right upper abdominal pain, fever, or jaundice.

• Acute kidney injury – dehydration from nausea, vomiting, or diarrhoea can lead to kidney problems. Maintain adequate fluid intake and seek medical advice if you experience symptoms of dehydration (dark urine, dizziness, reduced urination).

• Diabetic retinopathy – rapid improvement in blood glucose control, particularly with semaglutide, may temporarily worsen diabetic retinopathy in patients with pre-existing eye disease. Regular eye screening is important.

• Mental health effects – for weight-management indications (Saxenda®, Wegovy®), there have been reports of suicidal ideation and behaviour. Patients and carers should be alert to changes in mood or behaviour and seek medical advice promptly if concerns arise.

• Pancreatitis – rare but serious. Patients should seek immediate medical attention if experiencing severe, persistent abdominal pain radiating to the back.

• Thyroid concerns – GLP-1 receptor agonists carry a warning (not a contraindication) regarding thyroid C-cell tumours observed in animal studies. Patients with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 (MEN2) should discuss this with their healthcare professional. Seek medical advice if you develop symptoms such as a lump in the neck, difficulty swallowing, or persistent hoarseness.

Pregnancy and breastfeeding: GLP-1 receptor agonists are not recommended during pregnancy or breastfeeding. Women of childbearing potential should use effective contraception during treatment and discuss family planning with their healthcare professional.

When to contact your GP, diabetes team, or healthcare professional:

• Severe or persistent nausea and vomiting preventing adequate fluid or food intake

• Signs of dehydration (dark urine, dizziness, reduced urination)

• Severe abdominal pain, particularly if accompanied by vomiting, or right upper abdominal pain with fever

• Symptoms of hypoglycaemia that don't resolve with usual treatment

• Unexplained weight loss exceeding clinical targets

• Changes in mood or suicidal thoughts

• Any concerns about medication tolerance or effectiveness

The MHRA continues to monitor the safety profile of incretin medications through the Yellow Card scheme. Patients and healthcare professionals are encouraged to report suspected side effects via the Yellow Card scheme at www.yellowcard.mhra.gov.uk or via the Yellow Card app. Regular follow-up appointments allow healthcare professionals to assess treatment response, adjust doses, monitor for complications, and provide ongoing support for lifestyle modifications that complement pharmacological therapy. (MHRA Drug Safety Updates; MHRA/EMC SmPCs for semaglutide and liraglutide; NHS medicines pages)

Frequently Asked Questions