Considerations and interactions with GLP-1 receptor agonists

People should be advised that GLP-1 RAs are prescription only medicines (POMs). 

GLP-1 RAs should only be sold or supplied using an appropriate legal mechanism such as a valid prescription issued by a qualified prescriber.

These include UK registered doctors, supplementary prescribers, and independent prescribers.

An MHRA alert highlights fake Ozempic (semaglutide) injections and Saxenda (liraglutide) injections have been found in the UK. In some cases, the product has contained insulin and risked hypoglycaemia in the user.

If GLP-1 RAs are prescribed privately, they must be supplied by a registered pharmacy to avoid the risk of receiving a fake medicine.

If using an online supplier, refer to GPhC advice on how to keep safe when getting medicines online.

Tirzepatide injections contain benzyl alcohol.

People with reduced liver or kidney function should be counselled on the risk of metabolic acidosis from accumulation of benzyl alcohol over time.

There is no consensus on the place of GLP-1 RAs following bariatric surgery. They may have a place prior to bariatric surgery.

People considering bariatric surgery should be referred to specialist weight management clinics for assessment and management advice.

See our article on Considerations for using medicines following bariatric surgery for further support.

An MHRA alert highlights the risk of diabetic ketoacidosis in people with type 2 diabetes using a GLP-1 RA with insulin. These people had their insulin dose rapidly reduced or discontinued.

Healthcare professionals are reminded to advise people with type 2 diabetes to self-monitor their blood glucose when insulin doses are adjusted. Especially when GLP-1 RAs are started or the insulin dose reduced.

When insulin is reduced, use a stepwise approach.

The main concern with GLP-1 RAs and hormone replacement therapy (HRT) relates to the potential for reduced absorption of oral progestogens and the reduction in protection from endometrial cancer.

There is no robust data to suggest GLP-1 RAs affect the oral progestogen component of HRT, dosing requirements, bleeding patterns or endometrial risk.

People using GLP-1 RAs for weight loss may require a full medicines review in case the dose of other medicines require adjusting. For example, direct oral anticoagulant choice may change in people with extremes body weight.

An MHRA alert highlights the potential misuse of GLP-1 RAs for unlicensed indications such as weight loss in people who are not overweight or obese.

The benefits and risks of using GLP-1 RAs outside their licensed indications are unknown.

Not all GLP-1 RA injections are supplied with manufacturer needles. For example, Mounjaro (tirzepatide) pre-filled pens do not include needles.

Always check section 6.5 of the Summary of Product Characteristics (SmPC) to confirm whether needles are included.

If needles are not listed, supply them separately. Consider any relevant allergies when selecting appropriate needles.

The MHRA advise GLP-1 RAs should not be taken during pregnancy due to a lack of human safety data.  They advise contraceptive use throughout GLP-1 RA treatment as a cautionary measure.

The MHRA provide guidance on the length of time the GLP-1 RA should be stopped before trying to get pregnant.

The UK Teratology Information Service (UKTIS) also states the evidence for GLP-1 RA safety in pregnancy is limited. However, they suggest placental transfer is not expected due to the high molecular masses of GLP-1 RAs.

Healthcare professionals should consider contacting UKTIS for patient-specific advice.

The MHRA advise GLP-1 RAs should not be taken by people who are breastfeeding due to a lack of safety data.

Healthcare Professionals should consider contacting the SPS Medicines Advice Service for patient-specific advice.

An MHRA alert highlights an increased risk of residual gastric contents aspiration, even after pre-operative fasting, due to GLP-1 RAs delaying gastric emptying.

People undergoing planned surgery should be encouraged to disclose any use of GLP-1 RAs before surgery.

The potential risk of aspiration should be assessed by the anaesthetist, regardless of indication.

The MHRA states there is no association between GLP-1 RAs and suicidal behaviour, suicidal ideation, self-injury and depression. This is based on the MHRA review of post marketing data, clinical trial data, epidemiological studies and scientific literature.

There is very little data on how to switch between GLP-1 RAs, including brands containing the same type of GLP-1 RA.

Refer to the SmPC for advice on starting doses and dose escalations.

Some dose escalations, such as semaglutide (Wegovy) and tirzepatide (Mounjaro) for weight management can take weeks or months to reach steady state.

The Association of British Clinical Diabetologists (ABCD) provide guidance on switching some GLP-1 RAs in people with diabetes.

Semaglutide

Subcutaneous semaglutide 0.5mg once weekly is comparable to oral semaglutide 14 mg once daily.

Due to the high pharmacokinetic variability of oral semaglutide, the effect of switching between oral and subcutaneous semaglutide cannot easily be predicted.

Rybelsus

People taking Rybelsus (semaglutide) tablets may notice a change in their product appearance.

The original Rybelsus tablets were oval shaped and the new formulation are round tablets.

The round tablets have greater bioavailability allowing for smaller doses. For example, 3mg of the oval Rybelsus tablet is bioequivalent to 1.5mg of the round Rybelsus tablet.

There is a risk of overdose and increase in side effects if people switching Rybelsus formulation are not counselled. Inform people of the change when prescribing and dispensing Rybelsus and supply the new formulation against newly started Rybelsus prescriptions.

The College of Sexual & Reproductive Healthcare (CoSRH) advise there is no evidence that dulaglutide, exenatide, liraglutide, lixisenatide, or semaglutide, reduce the effectiveness of oral contraception such as the combined oral contraceptive (COC) pill or the progestogen only pill (POP).

Tirzepatide

The CoSRH advise caution with tirzepatide and oral contraceptive use.

Tirzepatide is currently the only GLP-1 RA found to reduce the effects of oral contraceptives.

Women of child bearing age using tirzepatide should be advised to switch to a non-oral contraceptive method or add a barrier method of contraception, such as condoms, for 4 weeks after starting tirzepatide and for 4 weeks after any dose increase.

Non-oral contraceptives

No additional barrier methods are needed for contraceptives that are not taken orally such as patches, rings and implants.

Emergency contraceptive

The CoSRH advise the copper IUD is the most effective emergency contraception. There is no direct evidence regarding the effect of GLP-1 RAs on emergency hormonal contraception.

The British Menopause Society (BMS) advise in overweight, obese and women with diabetes, transdermal oestrogen is preferred as hormone replacement therapy (HRT). This is due to transdermal oestrogen having no effect on venous thromboembolism (VTE) risk, unlike oral oestrogen.

Transdermal HRT is not affected by GLP-1 RAs.

Consider switching women who are using oral HRT and prescribed GLP-1 RAs to a transdermal HRT.

Use GLP-1 RAs with caution in people who are taking medicines which are time critical, such as levodopa for Parkinson’s disease.

GLP-1 RA use may be an additional factor when assessing the risk of toxicity or loss of efficacy in people taking medicines with a narrow therapeutic window. These people may require additional monitoring.