sodium-glucose co-transporter 2 (SGLT2) inhibitors
- Adjunct to diet and exercise in the management of type 2 diabetes mellitus.
- May be used with other antidiabetic agents.
Inhibits proximal renal tubular sodium-glucose co-transporter 2 (SGLT2) which determines reabsorption of glucose from the tubular lumen. Inhibits reabsorption of glucose, lowers renal threshold for glucose and increases excretion of glucose in urine.
Improved glycemic control.
Absorption: 78% absorbed following oral administration.
Metabolism and Excretion: Extensively metabolized by UGT1A9 to inactive metabolites which are primarily excreted in urine. 15% excreted in feces as unchanged drug.
Half-life: 12.9 hr
TIME/ACTION PROFILE (decrease in HbA1c)
|PO||within 4 wk||12 wk||unknown|
- Severe renal impairment/end-stage renal disease/dialysis eGFR <60 mL/min/1.73 m2;
- Type 1 diabetes;
- Diabetic ketoacidosis;
- Active bladder cancer;
- Lactation: Avoid use, discontinue breastfeeding or discontinue dapagliflozin.
Use Cautiously in:
- History of pancreatitis, pancreatic surgery, reduced caloric intake due to illness or surgery, or alcohol abuse (↑ risk of ketoacidosis);
- Hypovolemia, chronic kidney disease, HF, or concurrent use of diuretics, NSAIDs, ACE inhibitors, or ARBs (↑ risk of acute kidney injury);
- Geri: ↑ risk of adverse reactions related to ↓ intravascular volume;
- Hypotension (correct prior to treatment, especially if eGFR 30–60 mL/min, age >65 yr, or concurrent use of loop diuretics, ACE inhibitors, or ARBs
- History of bladder cancer;
- OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
- Pedi: Safe and effective use in children <18 yr has not been established.
Adverse Reactions/Side Effects
CV: volume depletion
GU: UROSEPSIS, acute kidney injury, genital mycotic infections, ↑ urination, renal impairment, urinary tract infection (including pyelonephritis)
Endo: hypoglycemia (↑ with other medications)
F and E: KETOACIDOSIS, hyperphosphatemia
Misc: HYPERSENSITIVITY REACTIONS(INCLUDING ANGIOEDEMA, OR URTICARIA)
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
PO (Adults) 5 mg once daily, may be increased to 10 mg once daily.
Tablets: 5 mg, 10 mg
In Combination with: metformin (Xigduo XR); saxagliptin (Qtern). See combination drugs
- Observe for signs and symptoms of hypoglycemic reactions (sweating, hunger, weakness, dizziness, tremor, tachycardia, anxiety), especially in patients taking insulin or other hypoglycemic agents.
- Monitor BP after initiating and periodically during therapy; may cause hypotension.
- Monitor for signs and symptoms of urinary tract infection (burning during urination, frequent urination, urgency, pain in pelvis, blood in urine, fever, back pain, nausea, vomiting) during therapy. Treat promptly.
Lab Test Considerations: Monitor serum glucose and glycosylated hemoglobin periodically during therapy to evaluate effectiveness of treatment.
- Evaluate renal function prior to starting and periodically during therapy; may cause ↑serum creatinine and ↓ eGFR.
- May cause ↑ LDL cholesterol.
- May cause an ↑ hematocrit and serum phosphorous.
- Will cause urine to test positive for glucose.
Overdose is manifested by symptoms of hypoglycemia. Mild hypoglycemia may be treated with administration of oral glucose. Treat severe hypoglycemia with IV D50W followed by continuous IV infusion of more dilute dextrose solution at a rate sufficient to keep serum glucose at approximately 100 mg/dL.
- Patients stabilized on a diabetic regimen who are exposed to stress, fever, trauma, infection, or surgery may require administration of insulin.
- PO Administer once daily in the morning without regard to food.
- Instruct patient to take medication at same time each day. Take missed doses as soon as remembered unless almost time for next dose; do not double doses. Advise patient to read Medication Guide before starting and with each Rx refill in case of changes.
- Explain to patient that this medication controls hyperglycemia but does not cure diabetes. Therapy is long term.
- Inform patient dapagliflozin may cause dehydration and hypotension. Maintain adequate hydration and notify health care professional if dizziness, fainting, weakness or orthostatic hypotension occur.
- Advise patient to notify health care professional if signs and symptoms of urinary tract infections or genital mycotic infections; females (vaginal odor, white or yellowish vaginal discharge, vaginal itching), males (rash or redness of glans or foreskin of penis, foul smelling discharge from penis, pain in skin around penis) occur. Instruct patient on treatment options and when to notify health care professional.
- Review signs of hypoglycemia and hyperglycemia with patient. If hypoglycemia occurs, advise patient to drink a glass of orange juice or ingest 2–3 tsp of sugar, honey, or corn syrup dissolved in water or an appropriate number of glucose tablets and notify health care professional.
- Encourage patient to follow prescribed diet, medication, and exercise regimen to prevent hypoglycemic or hyperglycemic episodes.
- Instruct patient in proper testing of serum glucose and ketones. These tests should be closely monitored during periods of stress or illness and health care professional notified if significant changes occur.
- Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
- Advise patient to inform health care professional of medication regimen prior to treatment or surgery.
- Advise patient to notify health care professional promptly if signs and symptoms of hypersensitivity reactions (rash; raised red patches on skin; swelling of face, lips, tongue, throat; difficulty breathing or swallowing) or bladder cancer (blood or red color in urine, painful urination) occur.
- Advise patient to carry a form of sugar (sugar packets, candy) and identification describing disease process and medication regimen at all times.
- Rep: Insulin is the recommended method of controlling blood sugar during pregnancy. Counsel female patients to use a form of contraception other than oral contraceptives and to notify health care professional promptly if pregnancy is planned or suspected. May cause fetal harm in 2nd or 3rd trimester.
- Emphasize the importance of routine follow-up exams.
Control of blood glucose levels without the appearance of hypoglycemic or hyperglycemic episodes.
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