What are the side effects of dapagliflozin (SGLT2 inhibitor)?

Side Effects of Dapagliflozin (SGLT2 Inhibitor)

Dapagliflozin commonly causes genital mycotic infections and urinary tract infections, with less frequent but serious side effects including diabetic ketoacidosis, volume depletion, and rare cases of necrotizing fasciitis of the perineum. 1

Common Side Effects

• Genital mycotic infections: Most frequent side effect, particularly in women (13.2% of women vs 3.3% of men) and those with prior history of such infections (21.6% vs 7.3% in those without prior history) 2
• Urinary tract infections: Can be serious and lead to hospitalization, though clinical trials show no significant difference in rates compared to placebo 1
• Changes in urination patterns: Including urgent need to urinate more frequently, in larger amounts, or at night 1
• Upper respiratory infections: Including stuffy or runny nose and sore throat 1

Serious Side Effects

• Diabetic ketoacidosis: Can occur even with normal or only mildly elevated blood glucose levels ("euglycemic diabetic ketoacidosis") 3, 1
• Volume depletion and hypotension: Particularly in patients with renal impairment, those on diuretics, or elderly patients 3
• Necrotizing fasciitis of the perineum (Fournier's gangrene): Rare but serious bacterial infection that may lead to hospitalization, multiple surgeries, and death 1
• Serious hypersensitivity reactions: Including urticaria, anaphylactic reactions, and angioedema 1

Metabolic and Laboratory Effects

• Initial eGFR decline: Typically 3-5 mL/min/1.73 m² within first 4 weeks of therapy, which is usually reversible and not an indication to discontinue therapy 3
• Hypoglycemia: Risk increases when used with insulin or insulin secretagogues (e.g., sulfonylureas) 1
• Positive urine glucose tests: Due to mechanism of action, patients will test positive for glucose in urine 1

Risk Mitigation Strategies

• For genital mycotic infections: Provide hygienic counseling; most infections are mild to moderate, easily treated, and infrequently recur 3, 4
• For diabetic ketoacidosis: Implement sick day rules and insulin guidance; consider withholding during prolonged fasting, surgery, or critical illness 3
• For volume depletion: Consider reducing diuretic doses in patients at risk for hypovolemia or hypotension 3
• For hypoglycemia: Reduce doses of insulin or insulin secretagogues when adding dapagliflozin, particularly in patients with eGFR >45 mL/min/1.73 m² 3

Special Population Considerations

• Renal impairment: Reduced efficacy when eGFR <45 mL/min/1.73 m²; monitor closely in patients with renal impairment 3
• Elderly patients: Higher risk for volume depletion and hypotension; monitor carefully 5
• Pregnancy: Potential risk to fetus; not recommended during pregnancy 1
• Breastfeeding: Not recommended during breastfeeding 1

Beneficial Side Effects

• Weight loss: Consistent finding across clinical trials 6, 7
• Blood pressure reduction: Beneficial effect on both systolic and diastolic blood pressure 6
• Reduced hyperkalemia risk: Without causing hypokalemia 3
• Reduced fluid retention: Can facilitate use of other guideline-directed therapies 3

When to Discontinue

• If symptoms of ketoacidosis develop: Including nausea, vomiting, abdominal pain, difficulty breathing 3, 1
• If signs of serious allergic reaction occur: Stop immediately and seek emergency care 1
• If necrotizing fasciitis is suspected: Seek immediate medical attention for pain, tenderness, redness, or swelling in the genital or perianal area, especially with fever or malaise 1

Dapagliflozin has a favorable overall safety profile with most adverse effects being mild to moderate in severity, but awareness of potential serious complications is essential for appropriate patient selection and monitoring 4, 6.