SGLT2 Inhibitors (Empagliflozin, Dapagliflozin, Canagliflozin)

ED / ICU / Transport

• Arrives on the drug: It is a home medication. Find it on every medication list. It is not started or used for acute care in the field or ED.
• Hospital holds and restarts: The treating team decides. For the hold rules, see Contraindications & Precautions and Dosing.

Other Uses

• Type 2 diabetes, glycemic control: Add-on to diet and exercise, in adults and in patients aged 10 years and older (all three agents). Not for glycemic control in type 1 diabetes. Ketoacidosis risk is the reason.
• Heart failure: empagliflozin and dapagliflozin reduce cardiovascular death and hospitalization for heart failure in adults with heart failure.
• Chronic kidney disease: empagliflozin and dapagliflozin reduce sustained eGFR decline, end-stage kidney disease, cardiovascular death and heart failure hospitalization in adults with CKD at risk of progression. Not for CKD from polycystic kidney disease or with recent immunosuppressive therapy for kidney disease.
• Cardiovascular risk in type 2 diabetes: empagliflozin reduces cardiovascular death with established cardiovascular disease; canagliflozin reduces major adverse cardiovascular events; dapagliflozin reduces heart failure hospitalization with established disease or multiple risk factors.
• Diabetic nephropathy: canagliflozin reduces end-stage kidney disease, doubling of serum creatinine, cardiovascular death and heart failure hospitalization in type 2 diabetes with albuminuria over 300 mg/day.

Doses vary by protocol; follow local protocols and medical direction.

Available Forms

• Empagliflozin (Jardiance) tablets: 10 mg and 25 mg
• Dapagliflozin (Farxiga) tablets: 5 mg and 10 mg
• Canagliflozin (Invokana) tablets: 100 mg and 300 mg
• EMS / transport: not carried. Write down the agent, strength, time of last dose and any pending procedure on the home medication list.

Adult Dosing

Pediatric Dosing

Preparation & Administration

• Route and timing: oral. Empagliflozin and dapagliflozin may be taken with or without food. Canagliflozin is taken before the first meal of the day (label).
• Missed dose: Take it as soon as it is remembered. Do not double the next dose (dapagliflozin label).
• Temporary hold for surgery: withhold at least 3 days before surgery or procedures with prolonged fasting, if possible (empagliflozin, dapagliflozin, canagliflozin). Resume when clinically stable and eating and drinking (labels).

Contraindications

• Serious hypersensitivity to the drug or any excipient: angioedema or anaphylaxis (all three labels).

Precautions

• Type 1 diabetes: Not indicated for glycemic control. The label reports a markedly increased ketoacidosis risk in type 1 patients. Fatal ketoacidosis has occurred with empagliflozin.
• Ketoacidosis in type 2 diabetes: Pancreatic disorders (prior pancreatitis or pancreatic surgery) raise the risk. The triggers to watch for are insulin dose reduction or missed insulin, acute febrile illness, reduced calorie intake, ketogenic diet, surgery, volume depletion and alcohol abuse.
• Volume depletion and acute kidney injury: Risk runs higher with eGFR under 60 mL/min/1.73 m², older age or loop diuretics. Postmarketing reports include acute kidney injury that required hospitalization and dialysis.
• Genitourinary infection: urosepsis, pyelonephritis, genital mycotic infection and Fournier gangrene (necrotizing fasciitis of the perineum).
• Hypoglycemia: Risk is higher with insulin or a sulfonylurea. Lower the insulin or sulfonylurea dose when the SGLT2 inhibitor is started.
• Lower-limb amputation: The labels describe watching the feet for infections and ulcers. Canagliflozin's label reports a higher amputation risk versus placebo in the CANVAS trial.
• Bone fracture (canagliflozin): the label (section 5.7) reports increased fracture risk in CANVAS, as early as 12 weeks after starting. Consider fracture-risk factors before you start.
• Urine glucose: These drugs make the urine glucose test positive. Using urine glucose to monitor glycemic control is not recommended.

Hold / Reassess If

• Ketoacidosis suspected, at any blood glucose: Stop the drug, then evaluate and treat per protocol. Restart only after the ketoacidosis has resolved and the patient is stable and eating.
• Surgery or prolonged fasting: Withhold for at least 3 days beforehand, if possible. Reassess before restarting.
• Acute illness with vomiting, poor oral intake, fever or alcohol use: Withhold if possible. These predispose the patient to ketoacidosis (label).
• eGFR thresholds: empagliflozin not recommended for glycemic control at eGFR <30; dapagliflozin not recommended for glycemic control at eGFR <45 and not started for other indications at eGFR <25; canagliflozin initiation not recommended at eGFR <30.
• Symptomatic hypotension or signs of volume depletion: correct volume status and reassess the drug and any loop diuretic.
• Perineal or genital pain, tenderness, erythema or swelling with fever or malaise: stop the drug and evaluate urgently for Fournier gangrene (label).
• Hypersensitivity or angioedema: discontinue and treat promptly; monitor until signs resolve (label).

Common

• Genital mycotic infections and urinary tract infections.
• Increased urination and glucosuria. The glucosuria is the expected pharmacologic effect.
• Intravascular volume depletion: dizziness or symptomatic hypotension, most often in older patients or those on loop diuretics.
• A small early rise in serum creatinine and a fall in eGFR happen after starting. These changes usually stabilize (label laboratory section).

Serious / Life-Threatening

Overdose & Toxicity Management

• Overdose: there is no SGLT2-specific antidote on this page. Manage the effects (ketoacidosis, volume loss, hypoglycemia with insulin or sulfonylurea) per protocol. Consult a poison center per local policy.
• Ketoacidosis: see Diabetic Ketoacidosis. The labels note that glucose may be below 250 mg/dL, and that ketoacidosis and glucosuria may persist longer than expected. In euglycemic cases, glucose-containing fluids with insulin are used per protocol. The local protocol sets the dextrose start point, the insulin and potassium plan and the glucose target.
• Hypoglycemia: Dextrose and glucagon per protocol; see Hypoglycemia.

This page does not cover other combinations. Check an institutional drug-interaction resource.

• Pediatrics: Glycemic control is labeled from age 10 years. Use below age 10 is not established. Hypoglycemia risk is higher in this age group. The doses are in the Pediatric Dosing table.
• Pregnancy: The labels say these drugs are not recommended in the second and third trimesters. The basis is rat renal-development data, and human data are limited. The labels also flag the risk of poorly controlled diabetes in pregnancy.
• Lactation: Not recommended while breastfeeding (all three labels).
• Older Adults: Volume-depletion reactions were higher in patients aged 75 years and older (empagliflozin label). Adverse reactions also rise with reduced renal function. Review diuretics and blood pressure.
• Renal Impairment: The glycemic and non-glycemic thresholds are under Hold / Reassess If. Trials of these agents excluded patients on dialysis, and the labels give no dialysis dosing. Empagliflozin efficacy and safety trials did not enroll adults with eGFR below 20 mL/min/1.73 m² or on dialysis. Patients already enrolled in EMPA-REG OUTCOME, EMPEROR-Reduced, EMPEROR-Preserved and EMPA-KIDNEY did not have to stop when eGFR fell below 20 or when dialysis started (label, section 8.6). Dapagliflozin (DAPA-CKD, DELIVER) is the same at eGFR below 25 (label, section 8.6).
• Hepatic Impairment: Empagliflozin may be used in hepatic impairment. Exposure rises with Child-Pugh severity (about 23%, 47% and 75% AUC increase for mild, moderate and severe impairment).
• Obesity / Dosing Weight: Fixed doses. No weight adjustment.
• Type 1 Diabetes: Not indicated for glycemic control. See Precautions.

Mechanism of Action

• Target: Sodium-glucose cotransporter 2 in the proximal renal tubule. That transporter reabsorbs filtered glucose.
• Effect: Blocking it pushes glucose out in the urine (glucosuria). Blood glucose falls without insulin.
• Clinical consequence: The glucose-lowering effect weakens as eGFR falls. Intravascular volume depletion can cause symptomatic hypotension.

Pharmacokinetics

• Half-life: empagliflozin 12.4 h; dapagliflozin 12.9 h; canagliflozin 10.6 h (100 mg) and 13.1 h (300 mg). Canagliflozin reaches steady state in 4 to 5 days.
• Metabolism and elimination: Empagliflozin has no major metabolite. For dapagliflozin, less than 2% of the dose leaves in the urine as parent drug, and about 15% leaves in the feces as parent drug.
• Protein binding: empagliflozin about 86%.

Generic name

Empagliflozin; dapagliflozin; canagliflozin

Brand names (US)

Jardiance (empagliflozin); Farxiga (dapagliflozin); Invokana (canagliflozin). Combination products: Synjardy (empagliflozin with metformin); Invokamet (canagliflozin with metformin). Other SGLT2 products to recognize on a med list: ertugliflozin (Steglatro; Segluromet with metformin; Steglujan with sitagliptin); bexagliflozin (Brenzavvy); sotagliflozin (Inpefa); dapagliflozin with metformin (Xigduo XR); empagliflozin with linagliptin (Glyxambi; Trijardy XR with metformin). The same ketoacidosis cautions apply; check each label for the pre-surgery hold (ertugliflozin: at least 4 days)

Pharmacologic class

SGLT2 inhibitor

Therapeutic class

Antihyperglycemic; heart failure and CKD therapy

Controlled substance

Not controlled

ISMP High-Alert

No

Look-alike / sound-alike

None commonly reported