- ACRONYMS AND DEFINITIONS
- CHF - Congestive heart failure
- CV - Cardiovascular
- CVD - Cardiovascular disease
- GFR - Glomerular filtration rate
- HFrEF - Heart failure with reduced ejection fraction
- Met - metformin
- P = Drugs with pediatric dosing
- SGLT2 - Sodium-glucose co-transporter
- T2DM - Type 2 diabetes
Canagliflozin (Invokana®)
Dosage forms
Tablet
- 100 mg
- 300 mg
Dosing
Type 2 diabetes
- Starting: 100 mg once daily
- Maintenance: 100 - 300 mg once daily
- Max: 300 mg once daily
- Take before first meal of the day
Kidney disease
- GFR 45 - 59 ml/min: dose should not exceed 100 mg a day
- GFR < 45 ml/min: DO NOT USE
Liver disease
- Mild-to-moderate liver disease (Child-Pugh class A and B): no dosage adjustment is necessary
- Severe liver disease (Child-Pugh class C): has not been studied. Do not use.
Generic / Price
- NO/$$$$Dapagliflozin (Farxiga®)
Dosage forms
Tablet
- 5 mg
- 10 mg
Dosing
Glycemic control in type 2 diabetes
- CrCl ≥ 45 ml/min
- Starting: 5 mg once daily
- Maintenance: 5 - 10 mg once daily
- Maximum: 10 mg once daily
- May take without regard to food
- CrCl 25 - 44 ml/min
- Dapagliflozin is not likely to improve glycemic control in patients with CrCl < 45 ml/min
- CrCl < 25 ml/min
- Initiation is not recommended, however patients may continue 10 mg orally once daily to reduce the risk of eGFR decline, end stage kidney disease, CVD death and hospitalization for heart failure.
- On dialysis
- Contraindicated
Heart failure / Chronic kidney disease
- CrCl ≥ 45 ml/min
- Dosing: 10 mg once daily
- May take without regard to food
- CrCl 25 - 44 ml/min
- Dosing: 10 mg once daily
- May take without regard to food
- CrCl < 25 ml/min
- Initiation is not recommended, however patients may continue 10 mg orally once daily to reduce the risk of eGFR decline, end stage kidney disease, CVD death and hospitalization for heart failure.
- On dialysis
- Contraindicated
Liver disease
- No dose adjustment is necessary in mild, moderate, or severe liver disease
- Has not been studied extensively in patients with severe liver disease
Generic / Price
- NO/$$$$Empagliflozin (Jardiance®)
Dosage forms
Tablet
- 10 mg
- 25 mg
Dosing
Type 2 diabetes (adults and children ≥ 10 years old)
- Starting: 10 mg once daily
- Maintenance: 10 - 25 mg once daily
- Max: 25 mg once daily
- Take in morning with or without food
Heart failure (HFrEF and HFpEF)
- Dosing: 10 mg once daily
- Take in morning with or without food
Kidney disease
- Type 2 diabetes
- GFR ≥ 30 ml/min: no dose adjustment necessary
- GFR < 30 ml/min: not recommended. Likely to be ineffective for glucose control.
- Heart failure with reduced EF
- GFR ≥ 20 ml/min: no dose adjustment necessary
- GFR < 20 ml/min: has not been studied. Not recommended.
Liver disease
- No dose adjustment necessary
Generic / Price
- NO/$$$$Ertugliflozin (Steglatro™)
Dosage forms
Tablet
- 5 mg
- 15 mg
Dosing
Type 2 diabetes
- Starting: 5 mg once daily in the morning
- Maintenance: 5 - 15 mg once daily in the morning
- Max: 15 mg once daily in the morning
- Take in morning with or without food
Kidney disease
- GFR ≥ 45 ml/min: no dose adjustment necessary
- GFR < 45 ml/min: not recommended. Do not use in patients on dialysis.
Liver disease
- Child-Pugh A and B: no dosage adjustment is necessary
- Child-Pugh C: has not been studied. Not recommended.
Generic / Price
- NO/$$$$Invokamet® (canagliflozin + metformin)
Dosage forms
Tablet
- Canagliflozin - Metformin
- 50 mg - 500 mg
- 50 mg - 1000 mg
- 150 mg - 500 mg
- 150 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting: 50/500 mg twice daily
- Maintenance: 50/500 - 150/1000 mg twice daily
- Max: 150/1000 mg twice daily
- Take with food
Generic / Price
- NO/$$$$Invokamet® XR (canagliflozin + metformin ER)
Dosage forms
Tablet, extended-release
- Canagliflozin - Metformin ER
- 50 mg - 500 mg
- 50 mg - 1000 mg
- 150 mg - 500 mg
- 150 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting: 50/500 mg once daily
- Maintenance: 50/500 - 300/2000 mg once daily
- Max: 300/2000 mg once daily
- Take with morning meal
- Swallow tablets whole. Do not crush, cut, or chew.
Generic / Price
- NO/$$$$Segluromet® (ertugliflozin + metformin)
Dosage forms
Tablet
- Ertugliflozin - Metformin
- 2.5 mg - 500 mg
- 2.5 mg - 1000 mg
- 7.5 mg - 500 mg
- 7.5 mg - 1000 mg
Dosing
Type 2 diabetes
- Dosing: 2.5/500 mg - 7.5/1000 mg twice a day
- Max: 7.5/1000 mg twice a day
- Individualize starting dose based on patient's current regimen
- Take with meals
Generic / Price
- NO/$$$$Synjardy® (empagliflozin + metformin)
Dosage forms
Tablet
- Empagliflozin - Metformin
- 5 mg - 500 mg
- 5 mg - 1000 mg
- 12.5 mg - 500 mg
- 12.5 mg - 1000 mg
Dosing
Type 2 diabetes (adults and children ≥ 10 years old)
- Starting: 5/500 mg twice daily
- Maintenance: 5/500 - 12.5/1000 mg twice daily
- Max: 12.5/1000 mg twice daily
- Take with meals
Generic / Price
- NO/$$$$Synjardy® XR (empagliflozin + metformin ER)
Dosage forms
Tablet, extended-release
- Empagliflozin - Metformin ER
- 5 mg - 1000 mg
- 10 mg - 1000 mg
- 12.5 mg - 1000 mg
- 25 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting: 5/1000 mg once daily
- Maintenance: 5/1000 - 25/2000 mg once daily
- Max: 25/2000 mg once daily
- Take with morning meal
- Swallow tablets whole. Do not crush, cut, or chew.
Generic / Price
- NO/$$$$Xigduo™ XR (dapagliflozin + metformin ER)
Dosage forms
Tablet, extended-release
- Dapagliflozin - Metformin ER
- 5 mg - 500 mg
- 5 mg - 1000 mg
- 10 mg - 500 mg
- 10 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting: 5/500 mg once daily
- Maintenance: 5/500 - 10/2000 mg once daily
- Max: 10/2000 mg once daily
- Take with food in the morning
- Swallow tablets whole. Do not crush, cut, or chew.
- Inactive ingredients may be eliminated in the feces as a soft, hydrated mass that may resemble the original tablet
Generic / Price
- NO/$$$$Glyxambi® (empagliflozin + linagliptin)
Dosage forms
Tablet
- Empagliflozin - Linagliptin
- 10 mg - 5 mg
- 25 mg - 5 mg
Dosing
Type 2 diabetes
- Starting: 10/5 mg once daily
- Maintenance: 10/5 - 25/5 mg once daily
- Max: 25/5 mg once daily
- May take without regard to food
Generic / Price
- NO/$$$$Qtern® (dapagliflozin + saxagliptin)
Dosage forms
Tablet
- Dapagliflozin - Saxagliptin
- 5 mg - 5 mg
- 10 mg - 5 mg
Dosing
Type 2 diabetes
- Starting: 5/5 mg once daily
- Maintenance: 5/5 - 10/5 mg once daily
- Max: 10/5 mg once daily
- Take in the morning. May take without regard to food.
- Swallow whole. Do not crush, cut, or chew tablets.
Generic / Price
- NO/$$$$Steglujan® (ertugliflozin + sitagliptin)
Dosage forms
Tablet
- Ertugliflozin - Sitagliptin
- 5 mg - 100 mg
- 15 mg - 100 mg
Dosing
Type 2 diabetes
- Starting: 5/100 mg once daily
- Maintenance: 5/100 - 15/100 mg once daily
- Max: 15/100 mg once daily
- Take in the morning. May take without regard to food.
Generic / Price
- NO/$$$$Trijardy® XR (empagliflozin + linagliptin + metformin ER)
Dosage forms
Tablet, extended-release
- Empagliflozin - Linagliptin - Metformin ER
- 5 mg - 2.5 mg - 1000 mg
- 10 mg - 5 mg - 1000 mg
- 12.5 mg - 2.5 mg - 1000 mg
- 25 mg - 5 mg - 1000 mg
Dosing
Type 2 diabetes
- Starting:
- For patients switching from metformin with or without linagliptin, use a dosage that gives a similar total daily dose of metformin and a total daily dose of empagliflozin 10 mg and linagliptin 5 mg
- For patients switching from metformin and any regimen containing empagliflozin with or without linagliptin, use a dosage that gives a similar total daily dose of metformin, the same total daily dose of empagliflozin, and linagliptin 5 mg
- Max: Empagliflozin 25 mg/day | Linagliptin 5 mg/day | Metformin ER 2000 mg/day
- Take once daily with a meal in the morning
- Swallow tablets whole. Do not crush, cut, dissolve, or chew.
- Incompletely dissolved tablets may be seen in the feces. Patients should report this finding to their healthcare provider, and the provider should assess their glycemic control.
Generic / Price
- NO/$$$$- Kidney disease dosing
- Canagliflozin (Invokana®)
- GFR 45 - 59 ml/min: Dose should not exceed 100 mg a day
- GFR < 45 ml/min: DO NOT USE
- Dapagliflozin (Farxiga®)
- See dapagliflozin dosing above
- Empagliflozin (Jardiance®)
- Type 2 diabetes
- GFR ≥ 30 ml/min: no dose adjustment necessary
- GFR < 30 ml/min: not recommended. Likely to be ineffective for glucose control.
- Heart failure with reduced EF
- GFR ≥ 20 ml/min: no dose adjustment necessary
- GFR < 20 ml/min: has not been studied. Not recommended.
- Ertugliflozin (Steglatro™)
- GFR ≥ 45 ml/min: no dose adjustment necessary
- GFR < 45 ml/min: not recommended. Do not use in patients on dialysis.
- Liver disease dosing
- Canagliflozin (Invokana®)
- Mild-to-moderate liver disease (Child-Pugh class A and B): No dosage adjustment is necessary
- Severe liver disease (Child-Pugh class C): Has not been studied. Do not use.
- Dapagliflozin (Farxiga®)
- No dose adjustment is necessary in mild, moderate, or severe liver disease
- Has not been studied extensively in patients with severe liver disease
- Empagliflozin (Jardiance®)
- No dose adjustment necessary [7]
- Ertugliflozin (Steglatro™)
- Mild-to-moderate liver disease (Child-Pugh class A and B): No dosage adjustment is necessary
- Severe liver disease (Child-Pugh class C): Has not been studied. Not recommended.
- DRUG INTERACTIONS
- NOTE: The drug interactions presented here are NOT all-inclusive. Other interactions may exist. Drug interaction checkers provide the most efficient and practical way to check for interactions among multiple medications. A free interaction checker is available from Drugs.com (see Drugs.com interactions checker).
- All SGLT2 inhibitors
- Diuretics - SGLT2 inhibitors may potentiate the diuresis that occurs with diuretics. This may result in increased urination and volume depletion. Monitor patients for signs of dehydration when prescribing together. Diuretics include thiazide diuretics, loop diuretics, and aldosterone antagonists.
- Insulin and insulin secretagogues - the risk of hypoglycemia is increased when SGLT2 inhibitors are prescribed with insulin and insulin secretagogues (e.g. sulfonylureas, meglitinides). Monitor blood sugars closely when combining, particularly during initiation and dose changes.
- Lithium - SGLT2 inhibitors may reduce serum lithium concentrations. Monitor lithium levels closely during SGLT2 inhibitor initiation and dosage changes.
- Canagliflozin (Invokana™)
- Drugs that raise potassium levels
- Canagliflozin has the potential to raise potassium levels. This effect appears to be more pronounced with the 300 mg dose.
- It may interact with other drugs that raise potassium causing hyperkalemia (high blood potassium levels)
- Drugs that may raise potassium levels include:
- Aldosterone antagonists (spironolactone, eplerenone)
- Aliskiren (Tekturna®)
- ARBs (losartan, valsartan, etc.)
- Cyclosporine (Neoral®)
- ENaC inhibitors (triamterene, amiloride)
- Penicillin G potassium injection (1 million units contains 1.68mEq of potassium)
- Potassium supplements (K-Dur®, etc.)
- Tacrolimus
- Trimethoprim (part of Bactrim® and Septra®)
- UGT enzyme inducers
- Canagliflozin is primarily metabolized through O-glucuronidation by UGT1A9 and UGT2B4. UGT inducers may decrease canagliflozin exposure and reduce its effectiveness. When prescribing UGT inducers (e.g. rifampin, phenytoin, phenobarbital, ritonavir) with canagliflozin, the following is recommended:
- CrCl ≥ 60 ml/min: for patients taking 100 mg/day, increase to 200 mg/day. For patients taking 200 mg/day, increase to 300 mg/day.
- CrCl < 60 ml/min: for patients taking 100 mg/day, increase to 200 mg/day
- Digoxin - Canagliflozin has the potential to raise digoxin levels. Monitor levels appropriately.
- Metabolism and clearance
- Canagliflozin (Invokana®)
- UGT1A9 - substrate
- UGT2B4 - substrate
- CYP3A4 - minor substrate
- Dapagliflozin (Farxiga®)
- UGT1A9 - major substrate
- OAT3 - substrate
- P-glycoprotein - weak substrate
- Cytochrome P450 metabolism - undefined, minor pathway
- Empagliflozin (Jardiance®)
- UGT2B7, UGT1A3, UGT1A8, and UGT1A9 - substrate
- OAT3 - substrate
- OATP1B1 and OATP1B3 - substrate
- P-glycoprotein - substrate
- BCRP - substrate
- Ertugliflozin (Steglatro™)
- UGT2B7 and UGT1A9 - substrate
- UGT1A1 and UGT1A4 - weak inhibitor
- P-glycoprotein - substrate
- BCRP - substrate
- PRICE ($) INFO
Pricing legend
- $ = 0 - $50
- $$ = $51 - $100
- $$$ = $101 - $150
- $$$$ = > $150
- Pricing based on one month of therapy at standard dosing in an adult
- Pricing based on information from GoodRX.com®
- Pricing may vary by region and availability
Patient Assistance Programs for SGLT2 Inhibitors | ||||
---|---|---|---|---|
Drug | Manufacturer | Ships to | PAP info | Application |
Canagliflozin (Invokana®, Invokamet®, Invokamet® XR) | Johnson and Johnson | Pharmacy | Link | Link |
Dapagliflozin (Farxiga®, Qtern®, Xigduo XR®) | AstraZeneca | Patient or doctor | Link | Link |
Empagliflozin (Jardiance®, Glyxambi®, Synjardy®, Synjardy® XR) | Boehringer Ingelheim | Patient | Link | Link |
Ertugliflozin (Steglatro®, Steglujan®) | Merck | N/A | N/A | N/A |
- BIBLIOGRAPHY
- 1 - Canagliflozin PI
- 2 - Dapagliflozin PI
- 3 - Empagliflozin PI
- 4 - Ertugliflozin PI