SGLT2 inhibitors

What is it?

According to MedlinePlus, "SGLT2 inhibitors increase the amount of glucose passed in the urine", and may also lead to some weight loss and lower blood pressure in people with diabetes.

The MedlinePlus dapagliflozin page describes the mechanism of action as helping the kidneys remove glucose (sugar) and excess fluid through the urine, and the empagliflozin page describes the mechanism as the kidneys getting rid of more glucose in the urine.

The drugs MedlinePlus lists by name within the class: canagliflozin (Invokana), dapagliflozin (Farxiga) and empagliflozin (Jardiance). This page is limited to the class's drugs as they appear in its sources.

The NIDDK page on diabetes drugs does not mention the SGLT2 inhibitor class, so this page is limited to what appears in MedlinePlus, the NHS and the FDA label.

Uses

MedlinePlus notes on the dapagliflozin page that it is prescribed to lower blood sugar in people with type 2 diabetes, to reduce the risk of hospitalisation for heart failure in certain adults with diabetes, to treat heart failure, and to prevent worsening of kidney disease. The NHS notes that it is used in type 2 diabetes, heart failure and chronic kidney disease.

According to MedlinePlus, empagliflozin is prescribed to lower blood sugar in type 2, to reduce the risk of stroke, heart attack or death in certain people with diabetes, to reduce hospitalisation and death in heart failure, and to reduce worsening of kidney disease in people with kidney disease.

According to MedlinePlus, canagliflozin is prescribed to treat type 2 diabetes and to reduce the risk of stroke, heart attack, death and worsening of kidney disease in certain people.

The FDA label for Jardiance describes an indication to reduce the risk of cardiovascular death and hospitalisation for heart failure in adults, and to control blood sugar in type 2 "as an adjunct to diet and exercise". The NIDDK says on its heart and stroke page that "some diabetes drugs have been shown to reduce the risk of heart attacks and death in people at very high risk", without naming a specific class.

These uses do not mean that every patient is suited to the drug; each source has its own conditions, and the choice is decided by the doctor.

How it is used

Tablets taken by mouth. According to MedlinePlus they are taken once a day at a set time, with or without food for dapagliflozin, in the morning with or without food for empagliflozin, and before breakfast or the first main meal of the day for canagliflozin. The NHS gives the same advice for dapagliflozin: once daily at a set time with or without food. The dose and the method of stepwise increase are decided by the doctor according to your condition.

MedlinePlus stresses that the drug "helps control the condition but does not cure it", so it is continued even when you feel better as long as the doctor prescribes it.

MedlinePlus advises drinking plenty of water during use to reduce the risk of dehydration, and asking the doctor what to do in case of illness, infection, fever, severe stress or injury. The NHS notes that vomiting, diarrhoea or fever may cause dehydration, so consult the pharmacist or doctor.

Side effects

Common effects according to MedlinePlus: frequent urination (including at night) and increased thirst, and nasal congestion, sore throat, limb pain and constipation may also be mentioned depending on the drug. The NHS notes for dapagliflozin: fungal infection, back pain and frequent urination, and dizziness or fainting because of low blood sugar.

MedlinePlus says that with these drugs sugar in the urine increases, which is why "urinary infections and fungal infections" occur. It describes the symptoms: in women a vaginal odour or white or yellow discharge (which may be lumpy) or itching; in men redness, itching, swelling or rash on the penis, foul-smelling discharge or skin pain in the area. The FDA notes in the label that genital fungal infections in females were clearly higher than with placebo.

Symptoms of urinary infection according to MedlinePlus: frequent, urgent, burning or painful urination, cloudy or red, pink or brown urine, strong odour, passing a small amount of urine, fever, back pain, nausea or vomiting.

Ketoacidosis: MedlinePlus describes it as an emergency whose symptoms are nausea, vomiting, pain in the stomach area, tiredness or difficulty breathing, and states to test urine for ketones if possible even if blood sugar is not very high. The FDA notes in the Jardiance label that the risk "clearly increased" in patients with type 1 diabetes and that fatal cases have occurred, and that blood sugar may be lower than expected. The NHS lists its symptoms: intense thirst, confusion and sweet-smelling breath.

Dehydration: its signs according to MedlinePlus are dry mouth, dark urine, reduced sweating and dry skin. The FDA notes that these drugs may cause reduced fluid volume inside the vessels that sometimes shows as low blood pressure, and the risk is higher with impaired kidneys and in the elderly. MedlinePlus warns of dizziness or fainting when standing up quickly.

Necrotising infection of the perineum (Fournier's gangrene): MedlinePlus lists its symptoms as tiredness and weakness with fever and pain, tenderness, redness and swelling in the genitals or the area between them and the anus. The FDA describes it as a "rare life-threatening infection". The NHS mentions severe pain and swelling in the genital area.

Lower limb amputation: MedlinePlus says that empagliflozin and canagliflozin "may increase the risk of amputation of a toe, foot or leg", and calls for telling the doctor immediately of pain, sores, swelling or signs of infection in the legs or feet. This statement did not appear on the dapagliflozin page read here.

The NHS notes that severe allergy (anaphylaxis and angioedema) is possible. MedlinePlus mentions difficulty breathing or swallowing or swelling of the face, throat and tongue as emergency signs of allergy.

Warnings and precautions

According to MedlinePlus, tell your doctor before starting about: heart failure, pancreatic disease, urinary tract problems, low blood pressure, genital infection, kidney or liver disease, and for males circumcision status; as well as alcohol (especially excess), low-sodium or ketogenic diets, eating and drinking little, recent diarrhoea and vomiting, intense sun exposure and heavy sweating. The empagliflozin and canagliflozin pages add: peripheral vascular disease, foot ulcers, previous amputation, infection and osteoporosis depending on the drug.

According to the NHS for dapagliflozin: not suitable for people with type 1 diabetes, liver problems, an allergy to it, or recurrent urinary tract infection, and it is a prescription-only drug.

MedlinePlus says that alcohol may change blood sugar and increase side effects, so discuss it with the doctor. It advises telling the surgeon and dentist about the drug, and says the doctor may ask for it to be stopped at least three days before an operation, which is a decision the doctor makes.

Glucose may appear in a urine test because of the drug's own mechanism (MedlinePlus for empagliflozin).

Interactions

MedlinePlus states that the doctor may need to adjust the doses of your other medicines or monitor you closely, so tell them about all prescription and non-prescription medicines, vitamins, supplements and herbs.

The FDA notes in the Jardiance label that the risk of low blood sugar increases when it is used with insulin or insulin-secretagogue drugs.

For dapagliflozin the NHS lists among what may interact with it: furosemide, gliclazide, blood pressure–lowering drugs and lithium, and notes that alcohol may lower blood pressure. This page does not cover the complete list of interactions.

MedlinePlus notes that the doctor usually starts with metformin and may add another drug if blood sugar does not reach target; this is a general description of adding drugs and not details of a particular interaction.

Monitoring

MedlinePlus says of canagliflozin that the drug reduces the risk of worsening kidney disease but "requires monitoring through laboratory tests". The FDA notes in the Jardiance label that its use to control blood sugar is not recommended when the eGFR falls below a certain limit set by the label, and that the risk is higher with impaired kidneys. Monitoring relates to kidney function (creatinine and eGFR), and the doctor decides the testing schedule.

MedlinePlus advises monitoring blood sugar regularly and wearing something that identifies you as a person with diabetes (for empagliflozin).

Special situations

Pregnancy and breastfeeding: MedlinePlus says: "do not breastfeed while taking dapagliflozin", and if pregnancy occurs call your doctor, and advises telling them when planning pregnancy (canagliflozin). The NHS notes that dapagliflozin is avoided during pregnancy because of insufficient safety data and that it may pass into breast milk. In the Jardiance label: not recommended in the second and third trimesters or during breastfeeding because of the possible effect on kidney development.

Kidneys: MedlinePlus (diabetes medicine education) says: "if you have kidney disease, tell your provider before taking these drugs". The FDA notes that the risk is higher in people with impaired kidneys and the elderly with regard to reduced fluid volume.

Children: the NHS notes that dapagliflozin is suitable for adults and children aged ten and over, without detailing the indications; this page does not cover similar texts for the other drugs.

Common situations

A missed dose according to MedlinePlus: take it as soon as you remember unless the time for the next dose is near, in which case skip it and do not double. The NHS gives dapagliflozin a short window after the usual time (twelve hours). Check with the pharmacist for the rule specific to your drug.

MedlinePlus advises telling the doctor in case of illness, infection, fever, severe stress or injury to know how to handle the drug.

Common questions