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

Dapagliflozin Side Effects

Dapagliflozin is generally well-tolerated, but clinicians must be vigilant for diabetic ketoacidosis (which can occur even with normal glucose levels), genital mycotic infections, and volume depletion, while understanding that the initial eGFR decline is expected and typically not a reason to discontinue therapy. 1, 2

Serious Side Effects Requiring Immediate Attention

Diabetic Ketoacidosis (DKA)

• Life-threatening ketoacidosis can develop even with blood glucose <250 mg/dL ("euglycemic DKA"), requiring hospitalization and potentially leading to death 2
• High-risk scenarios include: prolonged fasting, surgery, critical illness, reduced insulin doses, excessive alcohol consumption, ketogenic diets, volume depletion, or intercurrent illness 3, 2
• Discontinue dapagliflozin 3 days before any elective or anticipated invasive procedures to prevent postoperative ketoacidosis 3
• Warning signs: nausea, vomiting, abdominal pain, tiredness, trouble breathing, even with normal blood glucose 2

Volume Depletion and Hypotension

• Occurs due to diuretic action, particularly in elderly patients (≥65 years), those on concurrent diuretics, or patients with renal impairment 1, 2
• Manifests as dizziness, lightheadedness, weakness, or orthostatic hypotension 2
• Consider reducing diuretic doses in at-risk patients rather than routinely discontinuing diuretics when initiating dapagliflozin 3, 1
• Sudden kidney injury has been reported in type 2 diabetes patients taking dapagliflozin 2

Necrotizing Fasciitis of the Perineum (Fournier's Gangrene)

• Rare but potentially fatal bacterial infection affecting the perineal area in both men and women with diabetes 2
• May require multiple surgeries and can lead to death 2
• Seek immediate medical attention for fever >100.4°F with pain, tenderness, swelling, or redness in the genital or perianal area 2

Serious Urinary Tract Infections

• Pyelonephritis and urosepsis requiring hospitalization have been reported 2
• Warning signs: burning with urination, urgency, frequency, pelvic pain, blood in urine, fever, back pain, nausea, or vomiting 2

Common Side Effects

Genital Mycotic Infections

• More common in females than males 1
• Female symptoms: vaginal odor, white/yellowish discharge (cottage cheese-like), vaginal itching 2
• Male symptoms (balanitis/balanoposthitis): redness, itching, swelling of penis, foul-smelling discharge, rash, pain; uncircumcised men may develop difficulty retracting foreskin 2
• Managed with proper genital hygiene and over-the-counter antifungal medications, though seek medical advice if symptoms persist 1, 2

Upper Respiratory Symptoms

• Stuffy or runny nose and sore throat 2

Changes in Urination

• Urgent need to urinate more often, in larger amounts, or at night 2
• Urine will test positive for glucose due to mechanism of action 2

Metabolic and Laboratory Effects

Initial eGFR Decline

• Expected decrease of 3-5 mL/min/1.73 m² within first 4 weeks of therapy 3, 1
• This decline is typically reversible, with kidney function generally returning to baseline in following weeks and remaining stable during continued therapy 3
• This initial "eGFR dip" is NOT an indication to discontinue therapy 1
• Long-term data through 102 weeks shows stable renal function with minimal differences from placebo 4

Hypoglycemia Risk

• Low risk when used as monotherapy 2
• Increased risk when combined with sulfonylureas or insulin, requiring dose reduction of these agents 2
• Symptoms: headache, confusion, hunger, shaking, drowsiness, dizziness, fast heartbeat, weakness, sweating, irritability 2

Special Population Considerations

Renal Impairment

• Reduced glycemic efficacy when eGFR <45 mL/min/1.73 m² 3, 1
• Use not recommended for glycemic control when eGFR <45 mL/min/1.73 m² 3
• Contraindicated when eGFR <30 mL/min/1.73 m² or on dialysis 3
• Renal adverse events occur more frequently in patients with moderate renal impairment (eGFR 30 to <60 mL/min/1.73 m²) 4

Elderly Patients (≥65 years)

• Higher risk for volume depletion, hypotension, and renal adverse events 4
• Requires closer monitoring 1

Pregnancy and Lactation

• Contraindicated in pregnancy due to potential fetal risk 2
• Not recommended while breastfeeding 2

Serious Allergic Reactions

• Urticaria, anaphylaxis, and angioedema have been reported 2
• Stop dapagliflozin immediately and seek emergency care if allergic reaction symptoms develop 2

Beneficial Effects Worth Noting

• Reduced hyperkalemia risk without causing hypokalemia 1
• Reduced fluid retention facilitates use of other guideline-directed therapies 1
• Modest blood pressure reduction 5
• Body weight reduction 6, 5

Critical Monitoring and Patient Education

• Educate patients on sick day rules: reduce food/liquid intake, vomiting, diarrhea, or prolonged sun exposure warrant immediate medical contact 2
• If a dose is missed, take as soon as remembered unless almost time for next dose; never double dose 2
• Most common renal event is serum creatinine increase, though serious renal events are rare (0.2% over 102 weeks) 4