Dapagliflozin Side Effects
Dapagliflozin is generally well tolerated with a low risk of hypoglycemia, but carries important risks including genital mycotic infections, volume depletion, urinary tract infections, and rare but serious diabetic ketoacidosis that can occur even with normal blood glucose levels. 1
Common Side Effects
Genital mycotic infections are among the most frequent adverse events, occurring more commonly in females (vaginal yeast infections) and males (balanitis or balanoposthitis), with symptoms including vaginal itching, discharge, or penile redness and swelling 1
Increased urination occurs due to the osmotic diuresis mechanism, with patients experiencing urgent need to urinate more often, in larger amounts, or at night 1
Upper respiratory symptoms including stuffy or runny nose and sore throat are commonly reported 1
Volume depletion and hypotension occur in approximately 5.7% of patients, particularly in elderly patients, those on diuretics, or those with renal impairment, manifesting as dizziness, lightheadedness, or orthostatic symptoms 2, 1
Serious but Less Common Side Effects
Diabetic ketoacidosis (DKA) is rare (0.2%) but life-threatening and can occur even with blood glucose levels less than 250 mg/dL (euglycemic DKA), requiring immediate medical attention if patients develop nausea, vomiting, abdominal pain, tiredness, or trouble breathing 2, 1
Necrotizing fasciitis of the perineum (Fournier's gangrene) is an extremely rare but serious bacterial infection requiring immediate medical attention if patients develop fever, malaise, pain, tenderness, swelling, or redness in the genital or perineal area 1
Serious urinary tract infections including pyelonephritis and urosepsis requiring hospitalization have been reported, with symptoms including burning with urination, urgency, pelvic pain, blood in urine, fever, or back pain 1
Acute kidney injury has been reported, particularly in the context of volume depletion, with rates of approximately 1.6% in clinical trials 2
Serious allergic reactions including urticaria, anaphylaxis, and angioedema have occurred and require immediate discontinuation of the medication 1
Metabolic and Laboratory Effects
Initial eGFR decline of 3-5 mL/min/1.73 m² typically occurs within the first 4 weeks of therapy but is generally reversible and not an indication to discontinue treatment 3, 4
Hypoglycemia risk is low when dapagliflozin is used alone (0.3%), but increases when combined with sulfonylureas or insulin, requiring dose adjustments of these agents 2, 1
Positive urine glucose tests will occur due to the drug's mechanism of action and should not be interpreted as treatment failure 1
Adverse Events Comparable to Placebo
Renal impairment occurred at similar rates to placebo (5.5% vs 6.5%) in long-term studies 2
Bone fractures showed no increased risk compared to placebo (2.2% vs 2.1%) 2
Urinary tract infections occurred at rates similar to placebo (2.3% vs 2.7%) in heart failure trials 2
Special Population Considerations
Elderly patients (≥65 years) are at higher risk for volume depletion and hypotension and require careful monitoring, though efficacy and safety are maintained across all age groups including octogenarians 3, 1, 5
Patients with renal impairment (eGFR <45 mL/min/1.73 m²) experience reduced glycemic efficacy, though cardiovascular and renal benefits persist; the drug was studied down to eGFR 25 mL/min/1.73 m² in DAPA-CKD 3, 6
Pregnant patients should be advised of potential fetal risks and discontinue dapagliflozin immediately 1
Breastfeeding is not recommended while taking dapagliflozin 1
Risk Mitigation Strategies
For DKA prevention: Implement sick day rules including withholding dapagliflozin during prolonged fasting, surgery, critical illness, or ketogenic diets 3, 1
For volume depletion: Consider reducing diuretic doses in at-risk patients and ensure adequate hydration, particularly during illness, heat exposure, or reduced oral intake 3, 1
For genital infections: Counsel patients on proper genital hygiene and provide information about over-the-counter antifungal treatments, with instructions to seek medical attention if symptoms persist 1
Overall Safety Profile
In the DAPA-HF trial, 74.1% of patients experienced at least one adverse event compared to 76.2% with placebo, with discontinuation rates due to adverse events being similar (4.7% vs 4.7%) 2. The medication demonstrated consistent safety across diverse patient populations including those with and without diabetes, cardiovascular disease, and chronic kidney disease 2, 7, 6, 8.