GLP-1 receptor agonists

What is it?

According to MedlinePlus: "GLP-1 agonists are a class of drugs used to treat type 2 diabetes by lowering blood sugar". They are synthetic hormones that mimic natural GLP-1, a gut hormone released after eating, giving the brain a signal of fullness, stimulating the pancreas to release insulin and slowing stomach emptying.

The MedlinePlus drug pages describe them as "incretin mimetics" that help the pancreas release the right amount of insulin and slow stomach emptying (semaglutide).

The drugs as MedlinePlus lists them within the class: dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide and tirzepatide (injections, most of them weekly), with oral daily semaglutide tablets (Rybelsus) for diabetes. The MedlinePlus weight loss drugs page lists liraglutide (Saxenda), semaglutide (Wegovy) and tirzepatide (Zepbound). The NHS describes liraglutide and semaglutide as GLP-1 agonists.

The NIDDK says on its diabetes treatments page: these drugs prevent glucose rising after eating and drinking, and may reduce hunger and help with some weight loss, but "GLP-1 drugs are not a substitute for insulin". The page does not name specific drugs.

Uses

MedlinePlus mentions the class's uses: managing type 2 diabetes, weight loss in people with obesity, reducing the risk of serious cardiac events, and improving kidney disease in some people with diabetes.

Semaglutide according to MedlinePlus: to control blood sugar in type 2, to reduce cardiovascular risks in people with diabetes who have heart or blood vessel disease, and in people with obesity or overweight with heart disease, to prevent worsening of kidney disease in people with diabetes, to help with weight loss in people with obesity or overweight with related health problems, and for non-cirrhotic metabolic dysfunction–associated steatohepatitis (MASH). The NHS notes that semaglutide is used for obesity (Wegovy) or for type 2 diabetes (Ozempic and Rybelsus).

Liraglutide according to MedlinePlus: type 2 diabetes, reducing cardiovascular events in people with diabetes who have heart disease, and helping weight management in people with obesity. The NHS notes that it is also used to treat obesity together with diet and exercise.

Dulaglutide according to MedlinePlus: control of blood sugar in type 2 and reducing cardiovascular risks in people with heart disease or high risk factors. And exenatide: lowering blood sugar in type 2, and according to the page it may reduce the risks of heart, stroke and kidney complications.

MedlinePlus (weight loss drugs) says "not everyone who takes them loses weight", and that most people regain some or all of the weight after stopping them unless they make a permanent change to their lifestyle. The NHS stresses that semaglutide for weight loss is used together with exercise and a change of diet.

How it is used

Most drugs in the class are injections by pre-filled pen under the skin of the abdomen, thigh or upper arm with rotation of the injection site, and needles are not reused and pens or needles are never shared (MedlinePlus). Semaglutide is a weekly injection on the same day of the week, liraglutide a daily injection, dulaglutide weekly, and exenatide twice a day before meals according to their pages. The dose and the method of stepwise increase are decided by the doctor according to your condition.

MedlinePlus notes that the solution should be inspected before injecting (clear, colourless and free of particles for semaglutide), and that the doctor usually starts with a low amount then increases it gradually according to response. Storage instructions and refrigeration should be reviewed with the pharmacist and the package leaflet.

The NHS notes for semaglutide tablets: taken on waking, and the person waits at least half an hour before eating, drinking or taking other medicines.

MedlinePlus says the drug "helps control blood sugar and weight but does not cure", and it is continued even when you feel better as long as the doctor prescribes it, while keeping follow-up appointments.

Side effects

Common effects according to MedlinePlus: nausea, vomiting, diarrhoea, stomach pain, constipation, heartburn, belching and headache (semaglutide); the general page notes that the digestive effects are more marked, especially at higher doses as stated. The NHS notes: nausea, vomiting, constipation, diarrhoea, tiredness, injection site reactions and hair loss (semaglutide). In the FDA's Ozempic label: nausea, vomiting, diarrhoea, abdominal pain and constipation are the most common.

Pancreatitis: MedlinePlus describes it as "rare", and describes its sign as persistent pain beginning in the upper abdomen (left or middle) that may spread to the back with or without vomiting. The NHS notes severe abdominal or back pain that does not go away. The FDA says in the Ozempic label that acute pancreatitis was observed, some of it haemorrhagic and necrotising and some fatal.

Gallbladder disease: MedlinePlus and the FDA label mention gallstones and cholecystitis, and the NHS mentions gallstones or cholecystitis for liraglutide. Signs of a liver or gallbladder problem in MedlinePlus: upper stomach pain, yellowing of the skin or eyes, fever and clay-coloured stools.

Low blood sugar: the NHS and FDA note that the risk is higher when combined with other diabetes drugs such as insulin and insulin secretagogues. MedlinePlus describes its symptoms: dizziness, irritability, sweating, hunger, drowsiness, shakiness, weakness, headache, slurred speech, blurred vision, fast heartbeat.

Diabetic retinopathy: the FDA notes that its complications occurred more in those treated with Ozempic compared with placebo. The NHS notes worsening retinopathy and sudden loss of vision as serious effects, and MedlinePlus mentions changes in vision.

Severe allergy: the FDA, NHS and MedlinePlus mention anaphylaxis, angioedema, swelling of the eyes, face, mouth, tongue or throat, and difficulty breathing or swallowing.

MedlinePlus also mentions signs that need attention: passing little urine, swelling of the legs or feet, and fast or pounding heartbeat.

Warnings and precautions

Boxed warning: MedlinePlus says of semaglutide, liraglutide and dulaglutide that the drug "may increase the risk of thyroid tumours including a type of thyroid cancer", that the tumours appeared in rodents and their effect in humans is unknown (semaglutide). Anyone with a personal or family history of thyroid tumours or cancer or MEN 2 syndrome should not use it. It lists signs that call for immediate care: a lump or swelling in the neck, hoarseness, difficulty swallowing, shortness of breath. The FDA describes in the Ozempic label that the tumours are thyroid C-cell tumours in rodents and the relevance to humans is unknown, with contraindications in a history of medullary thyroid carcinoma (MTC), MEN 2, or severe hypersensitivity to the drug. This page does not cover boxed warnings for the rest of the drugs in the class, so check your drug's leaflet.

Before use, MedlinePlus advises telling the doctor about: a history of pancreatitis, gallstones or gallbladder, kidney or liver disease, diabetic retinopathy, severe stomach problems or gastroparesis, depression or suicidal thoughts (liraglutide), and recent diarrhoea, vomiting or inability to drink. The NHS adds that people with a history of acute pancreatitis or gastrointestinal problems such as gastroparesis or an allergy to GLP-1 agonists are mostly not suited to the drug, and notes that liraglutide is not suitable for those aged 75 and over.

The FDA notes that the drug delays stomach emptying and that aspiration of stomach contents into the lungs has occurred during procedures requiring anaesthesia. MedlinePlus advises telling the surgical team that you are using the drug before any operation.

The FDA warns that kidney injury is linked to dehydration from nausea, vomiting or diarrhoea, so attention is paid to fluids when severe digestive symptoms appear.

The NHS says that alcohol may increase nausea and vomiting with semaglutide. MedlinePlus (exenatide) states that the drug should be avoided by anyone with a history of severe bleeding due to low platelets.

Interactions

MedlinePlus states that the doctor may need to change the doses of your medicines or monitor you closely, so tell them everything you take of medicines, vitamins, supplements and herbs.

According to the FDA, someone receiving Ozempic with insulin or insulin secretagogues may have a higher risk of low blood sugar. The NHS notes that semaglutide may interact with warfarin, levothyroxine, insulin, metformin, gliclazide, narcotics and sedatives; this page does not cover the details of each interaction, so ask the pharmacist.

The NHS notes for liraglutide: avoid combining with another GLP-1 agonist, and it may interact with diabetes drugs, insulin and anaesthetic agents.

And MedlinePlus notes for exenatide that birth control pills and antibiotics are taken at least an hour before the injection.

Monitoring

The source pages did not mention a specific testing programme for the class. MedlinePlus advises monitoring for symptoms of low blood sugar and following up with the doctor, and the FDA notes that retinal, kidney, pancreatic and gallbladder complications are monitored clinically. The doctor decides the tests appropriate for you, including kidney function when there is dehydration or kidney disease.

Special situations

Pregnancy and breastfeeding: MedlinePlus (semaglutide) says tell the doctor if you are pregnant or breastfeeding, and if pregnancy occurs call them immediately, and that someone planning pregnancy stops the drug two months beforehand according to the page, which the doctor decides. The NHS notes that it is not used during pregnancy and breastfeeding (liraglutide and semaglutide), and the MedlinePlus entry for the class says: avoid pregnancy while on the drug. The weight loss drugs page says pregnant and breastfeeding women should not take diet drugs.

Kidneys: the MedlinePlus pages state that the doctor should be told of any kidney disease, and the FDA mentions the risk of kidney injury with dehydration. MedlinePlus notes that semaglutide is used to prevent worsening of kidney disease in people with diabetes.

Older and younger people: the NHS notes for liraglutide that most adults and children aged ten and over may use it, and that it is not suitable for those aged 75 and over; the decision is individual with the doctor.

Common situations

A missed dose according to MedlinePlus differs between drugs and indications: semaglutide has different timing rules for diabetes and for weight, and the dose is never doubled to make up for a missed one. The NHS notes timing rules for liraglutide and semaglutide, and a missed tablet dose is skipped. Ask the pharmacist about the rule for your drug.

Storing pens: MedlinePlus notes that pens are kept away from light and heat and usually in the refrigerator without freezing, and are disposed of after use through medicine take-back programmes; check the package leaflet.

Common questions