Get urgent medical help if you take an SGLT2 inhibitor and develop nausea, vomiting, abdominal pain, unusual tiredness or shortness of breath, even if your blood glucose is normal or only slightly raised (possible ketoacidosis). Also seek help the same day for pain, tenderness, redness or swelling of the genitals or the area between the genitals and anus together with fever or feeling unwell (possible Fournier's gangrene).
Key points
- SGLT2 inhibitors (gliflozins) make the kidneys pass glucose and sodium into the urine. Depending on the medicine, they are FDA-approved for type 2 diabetes, heart failure and chronic kidney disease (CKD), and dapagliflozin and empagliflozin are approved for heart failure and CKD whether or not the person has diabetes.
- Their glucose-lowering effect fades as kidney function falls, but the heart and kidney benefits continue at lower eGFR levels. Each medicine has its own eGFR rules.
- They can cause ketoacidosis with near-normal blood glucose. Pause them during acute illness, poor eating or drinking and before planned surgery: at least 3 days before for most, and at least 4 days for ertugliflozin.
- Genital thrush and urinary infections are the most common side effects. Fournier's gangrene is rare but life-threatening.
- They are not recommended in the second and third trimesters of pregnancy or while breastfeeding.
How they work
The SGLT2 transporter in the first part of the kidney tubule reabsorbs most of the glucose filtered by the kidneys. Blocking it sends glucose out in the urine (about 70 g a day with dapagliflozin in type 2 diabetes). The medicines also reduce sodium reabsorption. The labels describe how this may lower the load on the heart (pre-load and after-load), damp down sympathetic nervous activity and reduce pressure inside the kidney's filtering units. Sotagliflozin also blocks SGLT1 in the gut, which reduces absorption of glucose and sodium there and likely contributes to diarrhoea, one of its most common side effects.
Because the effect depends on glucose being filtered, these medicines rarely cause low blood sugar on their own. The risk rises when they are combined with insulin or a sulfonylurea, and the labels advise considering a lower dose of those medicines.
What each medicine is approved for
US FDA indications as of October 2026. Approved uses vary between countries.
| Medicine | FDA-approved uses | Kidney (eGFR) rule in the label |
|---|---|---|
| Dapagliflozin | Type 2 diabetes (adults and children 10 years and older); heart failure; CKD at risk of progression; reducing heart-failure hospitalisation in type 2 diabetes with cardiovascular disease or risk factors | Not recommended for glucose control below 45. For other uses, do not start below 25, but may continue if eGFR falls below 25. |
| Empagliflozin | Type 2 diabetes (adults and children 10 years and older); heart failure; CKD at risk of progression; reducing cardiovascular death in type 2 diabetes with established cardiovascular disease | Not recommended for glucose control below 30. Heart failure and CKD trials enrolled people with eGFR 20 and above. |
| Canagliflozin | Type 2 diabetes (adults and children 10 years and older); reducing major cardiovascular events in type 2 diabetes with cardiovascular disease; reducing kidney failure and cardiovascular events in diabetic kidney disease with albuminuria above 300 mg/day | Maximum 100 mg at eGFR 30 to 59. Do not start below 30; people with heavy albuminuria already taking it may continue. |
| Ertugliflozin | Glucose control in adults with type 2 diabetes | Not recommended below 45. |
| Sotagliflozin | Reducing cardiovascular death and heart-failure events in adults with heart failure, or with type 2 diabetes, CKD and other cardiovascular risk factors (FDA-approved in 2023) | Studies did not enrol people with eGFR below 25 or on dialysis. |
None of these medicines is approved in the US for glucose control in type 1 diabetes, because they markedly increase the risk of diabetic ketoacidosis in that group. Dapagliflozin and empagliflozin are not recommended for treating CKD caused by polycystic kidney disease, or in people who need or recently had immunosuppressive treatment for kidney disease, because they are not expected to work there.
Dosing principles
- Check kidney function and fluid status before starting. Correct dehydration first.
- Dapagliflozin: 10 mg once daily for heart failure and CKD. For glucose control, start at 5 mg and increase to 10 mg if needed.
- Empagliflozin: 10 mg once daily in the morning. It may be increased to 25 mg for extra glucose control only.
- Canagliflozin: 100 mg once daily before the first meal. It may be increased to 300 mg for glucose control only if eGFR is 60 or above. Enzyme inducers such as rifampicin, phenytoin, phenobarbital and ritonavir lower its levels, and the label gives a higher dose in that case.
- Ertugliflozin: 5 mg once daily in the morning, increased to 15 mg if needed.
- Sotagliflozin: 200 mg once daily, no more than 1 hour before the first meal, increased to 400 mg after at least 2 weeks if tolerated.
Main side effects and risks
Ketoacidosis, including with normal glucose
Fatal ketoacidosis has been reported with SGLT2 inhibitors in type 2 diabetes. The labels warn that blood glucose may be lower than expected, for example below 250 mg/dL (about 14 mmol/L), so ketoacidosis can be missed. Triggers include missed or reduced insulin doses, fever or acute illness, eating very little, a ketogenic diet, surgery, dehydration and heavy alcohol use. A history of pancreatitis or pancreatic surgery also raises risk. Symptoms are nausea, vomiting, abdominal pain, feeling generally unwell and shortness of breath. Glucose loss in the urine lasts about 3 days after the last dose, but ketoacidosis has been reported up to 2 weeks after stopping.
Sick days and surgery
- The labels advise withholding the medicine, where possible, during temporary situations that raise ketoacidosis risk, and restarting once the person is stable and eating and drinking normally.
- Before surgery or procedures with prolonged fasting, withhold dapagliflozin, empagliflozin, canagliflozin and sotagliflozin for at least 3 days, and ertugliflozin for at least 4 days, if possible.
- Ketone testing may be advised for people at higher risk. Check ketones if symptoms appear, whatever the glucose reading.
Genital and urinary infections
Genital fungal infections (thrush) in women and men, and urinary tract infections, are among the most common side effects. A previous history of these infections makes them more likely. Serious infections, including kidney infection and urosepsis, have needed hospital care. Report symptoms early so they can be treated promptly.
Fournier's gangrene
This is a rare, life-threatening flesh-eating infection of the perineum that needs urgent surgery. Cases have occurred in both women and men, and some were fatal. Anyone with pain, tenderness, redness or swelling in the genital or perineal area plus fever or malaise needs immediate assessment, and the medicine should be stopped if it is suspected.
Low blood volume and kidney function
Fluid loss can cause dizziness or low blood pressure and a temporary rise in creatinine. Acute kidney injury, sometimes needing dialysis, has been reported. The risk is higher with eGFR below 60, in older adults, with loop diuretics and with low blood pressure.
Lower-limb amputation
The current canagliflozin, empagliflozin and ertugliflozin labels carry this warning. In the CANVAS trials, amputations were about twice as common with canagliflozin as with placebo, mostly of toes and the mid-foot. Empagliflozin outcome trials showed a smaller imbalance. Risk is highest with previous amputation, peripheral artery disease or diabetic foot ulcers. Check the feet regularly and report any ulcer, infection or new pain. The canagliflozin label advises stopping if these occur. The canagliflozin label also lists bone fracture as a precaution.
Safety: what to check
- Contraindications: a previous serious allergic reaction (such as anaphylaxis or angioedema) to the medicine.
- Before starting: eGFR, fluid status and blood pressure; diuretic doses; type of diabetes (avoid in type 1 diabetes outside specialist care); history of pancreatitis, genital or urinary infections, foot ulcers or peripheral artery disease; alcohol use and diet (ketogenic diets raise ketoacidosis risk).
- Interactions: insulin and sulfonylureas (hypoglycaemia, so lower doses may be needed); lithium (levels may fall, so monitor more often when starting or changing the dose); diuretics (volume depletion); digoxin with canagliflozin (higher digoxin levels). Urine glucose and 1,5-anhydroglucitol tests become unreliable, so use blood tests or HbA1c instead.
- Monitoring: kidney function after starting and as clinically indicated, blood pressure, symptoms of dehydration, genital and urinary symptoms, and foot checks.
- Pregnancy: not recommended in the second and third trimesters, based on animal data showing effects on the developing kidney. Discuss planning a pregnancy with the prescriber, since poorly controlled diabetes and untreated heart failure also carry risks.
- Breastfeeding: not recommended. Human kidneys continue to mature during the first 2 years of life, so a breastfed infant could be at risk.
- Older adults: no dose change based on age alone, but low blood pressure, dizziness and kidney-related side effects are more common.
- Liver: empagliflozin may be used in liver impairment. Canagliflozin is not recommended in severe liver impairment.
Frequently asked questions
Why would I take an SGLT2 inhibitor if I do not have diabetes?
Dapagliflozin and empagliflozin are approved to reduce cardiovascular death and hospital admissions in heart failure, and to slow kidney decline in CKD, whether or not diabetes is present. Sotagliflozin is approved for heart failure. In these uses they are taken for heart and kidney protection, not for blood sugar.
My eGFR has dropped. Should I stop?
Not necessarily. A small early dip in eGFR can happen as fluid is lost. Low eGFR mainly reduces the glucose-lowering effect, and some labels allow people to continue for heart or kidney protection at lower eGFR levels. Let the prescriber decide based on your medicine and reason for taking it.
What should I do if I am vomiting or cannot eat?
Pause the medicine as agreed in your sick-day plan and restart once you are eating and drinking normally. Seek urgent care for vomiting, abdominal pain or breathlessness, even if your glucose is not very high, and ask for a ketone test.
Sources
- US FDA-approved labeling, dapagliflozin (Farxiga). DailyMed
- US FDA-approved labeling, empagliflozin (Jardiance). DailyMed
- US FDA-approved labeling, canagliflozin (Invokana). DailyMed
- US FDA-approved labeling, ertugliflozin (Steglatro). DailyMed
- US FDA-approved labeling, sotagliflozin (Inpefa). DailyMed
- US FDA, Drugs@FDA: Inpefa (sotagliflozin), NDA 216203. accessdata.fda.gov
This article is for education and does not replace advice from a doctor or pharmacist who knows the person's history, kidney function and other medicines.
