Background

Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are intestinal incretin hormones that are released from the distal ileum and colon in response to food intake.

In the body, GLP-1 and GIP play an important role in glucose homeostasis, stimulating insulin release and inhibiting glucagon release, resulting in a lowering of blood glucose. GLP-1 and GIP also have extra pancreatic effects, which include a slowing of gastric emptying and central effects on the brain, leading to satiety and reduced appetite.

GLP-1 and GIP agonists bind to and activate GLP-1 and GIP receptors to increase glucose dependent insulin secretion from the pancreas, suppress glucagon secretion and slow gastric emptying.

Table 1: Current GLP-1 agonists, their site of action and their clinical indications

Use of GLP-1 agonists in women of childbearing age

The Faculty for Sexual and Reproductive Health (FSRH) have issued a statement of recommendations in January 2025 regarding patients of childbearing age taking GLP-1 agonists. Their statement outlines that contraception must be used when taking a GLP-1 agonist as there is there is insufficient safety data on its use in pregnancy. If a patient becomes pregnant whilst taking one of these agents they should contact their doctor immediately for advice:

• Individuals using tirzepatide (Mounjaro) and oral contraception should switch to a non-oral contraceptive method, or add a barrier method of contraception, for four weeks after initiation and four weeks after each dose increase. Tirzepatide is the only GLP-1 agonist found to have a clinically significant effect on the bioavailability of oral contraceptives. This is thought to be due to tirzepatide having a longer duration of action than other GLP-1 agonists;

• No clinically relevant reduction in bioavailability of oral contraceptives (COCP or POP) has been observed with semaglutide, exenatide, liraglutide, dulaglutide or lixisenatide;
• There is no need to add a barrier method of contraception when using semaglutide, dulaglutide, exenatide, lixisenatide or liraglutide; and
• Alternatively, patients may wish to switch to a non-oral form of contraception, like the coil or implant, which are not as affected by GLP-1s.

Diarrhoea and vomiting due to GLP-1 agonists and oral contraception

Diarrhoea and vomiting could affect absorption of oral contraceptives which in turn may reduce effectiveness. Individuals who experience severe diarrhoea or vomiting during use of GLP-1 agonists should follow existing FSRH recommendations:

• Follow missed pill rules if vomiting occurs within three hours of pill taking (see manufacturer instructions) or if severe diarrhoea persists for >24 hours;
• If an individual has persistent vomiting or diarrhoea, consider non-oral contraception; and
• Consistent use of condoms is recommended.

GLP-1 agonists and emergency contraception 

There is no direct evidence or pharmacokinetic data regarding the effect of GLP-1 agonists on emergency hormonal contraception. The copper intrauterine device is the most effective method of emergency contraception, is not affected by diarrhoea and vomiting, and should always be offered where appropriate. As per current FSRH recommendations, double dose LNG-EC should be considered in individuals with a BMI over 26kg/m2 or weight over 70kg.

GLP-1 agonists and pregnancy planning

For patients trying to conceive, they are advised to continue using contraception for a defined “wash-out” period, i.e. the recommended duration between discontinuation of the GLP-1 agonist prior to a planned pregnancy.

Table 2: Washout periods of GLP-1 agonists

GLP-1 agonists and breastfeeding

GLP-1 agonists should not be taken when breastfeeding as there is there is insufficient safety data on its use in breastfeeding mothers.

GLP-1 agonists and eye disorders

It is advised that if patients experience a sudden loss of vision or rapidly worsening eyesight during treatment with GLP-1 agonists, they should contact their doctor immediately.

Diabetic retinopathy complications

Rapid improvement in glucose control has been associated with temporary worsening of diabetic retinopathy. Patients should be advised to report any symptoms of worsening retinopathy immediately, such as persistent or progressive blurred vision, loss of vision, new floaters or black spots in vision, to their doctor immediately.

Other eye conditions

In June 2025, the PRAC of the EMA concluded that non-arteritic anterior ischemic optic neuropathy (NAION), an eye condition that may cause loss of vision, is a very rare side effect of semaglutide (meaning it may affect up to 1 in 10,000 people taking semaglutide).

A recent 2025 report in JAMA ophthalmology, has also found that patients with longer durations of exposure to GLP-1 agonists were associated with a higher risk of developing neovascular age-related macular degeneration. However further investigation is required, as the mechanism of effect is not fully understood.

Common side effects seen with GLP-1 and GIP agonists

Pharmacists should be aware of the following side-effects to properly advise and help patients manage accordingly. These common side effects may impact the disease burden of people with type 2 diabetes and negatively affect adherence in all patient groups.

Gastrointestinal effects

Nausea, vomiting, diarrhoea, and abdominal pain are common across the class. However, nausea is likely at initiation and decreases over time.

Dehydration and renal function decline

Given that dehydration may occur as a result of nausea, vomiting and diarrhoea, pharmacists should advise patients on the potential for dehydration and a further risk of renal function decline. Patients, especially those with type 2 diabetes, should be advised to take precautions to avoid fluid depletion by maintaining adequate fluid intake of sugar-free fluids and, if unwell, following their usual sick day rules (advice for managing their diabetes during concurrent illness). The HSE provides a medication sick day leaflet on their website.

Risk of hypoglycaemia

Particularly when used in combination with sulfonylurea and/or insulin, consider dose reduction of these agents.

Acute pancreatitis

Patients should be counselled on characteristic symptoms (severe abdominal pain, nausea, diarrhoea, fever) and action to take. If the patient develops symptoms, they should be advised to discontinue their GLP-1 agonist and contact their healthcare professional immediately.

Injection site reactions

These can be minimised via education on, and assessment of, the correct injection technique and ongoing injection site rotation.

Using GLP-1 agonists around the time of a surgery or an operation

GLP-1 agonists are known to slow gastric emptying, which is a recognised side effect of these medicines. Patients taking GLP-1 agonists who are undergoing surgeries or procedures with general anaesthesia or deep sedation may have residual gastric contents despite preoperative fasting, which may leave them at higher risk of aspiration during surgery.

Patients taking a GLP-1 agonist, are advised to make sure they inform their healthcare team including the anaesthetist about their medicine prior to a surgical procedure.

Further information

Further information and resources can be found at:

• cosrh.org > News & Advocacy > News and press > FSRH Statement: Glucagon-like peptide-1 (GLP-1) agonists and oral contraception (7 February 2025);
• europa.eu > News > Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 2-5 June 2025 (6 June 2025); and
• HSE PCRS circulars 002/2023 and 002/2024.

References available