A summary of important cautions and side effects for the GIP and GLP-1 agonist tirzepatide and the GLP-1 agonist semaglutide; this includes specific information about contraception, conception, pregnancy and breastfeeding.

INTRODUCTION

SEMAGLUTIDE mimics the action of the body’s own hormone glucagon like peptide 1, (GLP-1), it is a GLP-1 receptor agonist.

TIRZEPATIDE mimics the action of gastric inhibitory polypeptide (GIP), it is a GIP receptor agonist, and also a GLP-1 receptor agonist.

These drugs:

  • increase the production of insulin when it is needed, and suppress the production of glucagon

  • reduce the amount of glucose being produced by the liver when it is not needed

  • slow down the speed at which your stomach digests food and empties

  • reduce your appetite

HOW CAN THEY HELP ME?

When combined with a healthy balanced diet and lifestyle, they can help reduce blood glucose levels and weight

CAN THEY CAUSE SIDE EFFECTS?

Most people who take these drugs long-term do not suffer any side effects. On commencing then nausea (feeling of sickness) is common for the first week but usually settles on its own accord. Other possible side effects include:

  • a sense of fullness

  • weight loss

  • diarrhoea

  • dizziness

  • headache

  • allopecia/ hair loss

  • allergies and skin rash are extremely unusual side effects

GASTROINTESTINAL ADVERSE REACTIONS

Tirzepatide has been associated with gastrointestinal adverse reactions, which include nausea and diarrhoea. These adverse reactions may lead to dehydration, which could lead to a deterioration in renal function including acute renal failure. Patients treated with tirzepatide should be advised of the potential risk of dehydration, due to the gastrointestinal adverse reactions and take precautions to avoid fluid depletion and electrolyte disturbances. This should particularly be considered in the elderly, who may be more susceptible to such complications.

PANCREATITIS

This is a rare but important side effect to be aware of is pancreatic inflammation (pancreatitis). If you have any severe tummy pain, persistent vomiting or severe weight loss you should contact your prescriber/ Dr Kelly, or your GP, sometimes you might need to go to hospital straight away. Do not take your next dose of the medication until the matter has been resolved.

The drugs have not been studied in patients who have had pancreatitis and in these patients they must be used with caution.

CONTRACEPTION

Tirzepatide delays gastric emptying which may affect absorption of concomitant oral medicines. Since reduced efficacy of oral contraceptives cannot be excluded, it is advised that female patients who are overweight or obese and using an oral contraceptive should add a barrier method of contraception, or switch to a non-oral contraceptive method for the first 4 weeks of treatment, and for 4 weeks after each dose increase.

CONCEPTION

Discontinue treatment before planned pregnancy at least:

  • one month with tirzepatide

  • two months with semaglutide

PREGNANCY

These drugs are not recommended in pregnancy. They should not be used in women who of childbearing potential who are not using contraception.

BREAST FEEDING

Tirzepatide – there is no information available. Tirzepatide is a large molecule, this suggests there will be limited excretion into milk; the drug molecule is likely to be partially destroyed in the infant's gastro-intestinal tract. An individual risk benefit discussion must be had with the patient to consider what to do, considering the benefit to the mother, the benefit to the baby of breastfeeding and potential risk from the drug

Semaglutide – the manufacturer advises it is avoided. The drug is present in milk in animal studies.

SAFETY

You should refer to the printed patient information/ summary of product characteristics for full safety information.

KETOACIDOSIS

The MHRA/CHM advice: GLP-1 receptor agonists: reports of diabetic ketoacidosis when concomitant insulin was rapidly reduced or discontinued (June 2019)

Serious and life-threatening cases of diabetic ketoacidosis have been reported in patients with type 2 diabetes mellitus on a combination of insulin and the GLP-1 receptor agonist exenatide, liraglutide, or dulaglutide, particularly after discontinuation or rapid dose reduction of concomitant insulin. The MHRA has not currently received any UK reports of diabetic ketoacidosis with the GLP-1 receptor agonists lixisenatide and semaglutide but this risk cannot be excluded. Similarly, this risk cannot be excluded for tirzepatide. Healthcare professionals are advised that any dose reduction of insulin should be done in a stepwise manner with careful blood glucose self-monitoring, particularly when GLP-1 receptor agonist therapy is initiated. Patients should be informed of the risk factors for and signs and symptoms of diabetic ketoacidosis, and advised to seek immediate medical attention if these develop.

CONTRAINDICATIONS

Tirzepatide and semaglutide are contraindicated in those with hypersensitivity to the active substance or to any of the excipients.

DRUG INTERACTIONS

Patients receiving tirzepatide or semaglutide in combination with a drug that stimulates insulin secretion e.g. a sulphonylurea, or insulin itself, may have an increased risk of hypoglycaemia. The risk of hypoglycaemia may be lowered by a reduction in the dose of the insulin secretagogue or insulin.

CAUTIONS

Tirzepatide and semaglutide are to be used with caution in patients with severe diabetic retinopathy. Semaglutide can make retinopathy worse in type 2 diabetes.

Tirzepatide has not been studied in patients with severe gastrointestinal disease, including severe gastroparesis, or in patients with non-proliferative diabetic retinopathy requiring acute therapy, proliferative diabetic retinopathy or diabetic macular oedema, and should be used with caution in these patients.

Every effort is made to ensure that this health and medication advice is accurate and up to date. It is for information only and supports your consultation, it does not obviate the need for that consultation and should not replace a visit to your doctor or health care professional.

The written advice is general in nature and in is not specific to individual patients and Dr Philip Kelly cannot accept any liability for actions arising from its use nor can he be held responsible for the content of any pages contained in any external link.