DECLARE-TIMI 58 Study Summary for Hospitalized Patients
What the Study Showed
Dapagliflozin 10 mg daily reduced heart failure hospitalizations by 27% and kidney complications by 47% in patients with type 2 diabetes, though it did not significantly reduce heart attacks or strokes. 1
Key Patient Population
The DECLARE-TIMI 58 trial enrolled 17,160 patients with type 2 diabetes who either had established cardiovascular disease (41%) or multiple cardiovascular risk factors (59%), with a median diabetes duration of 11 years and average age of 64 years. 2, 3
Primary Results Over 4.2 Years
Heart Failure Benefits:
- Hospitalization for heart failure was reduced by 27% (HR 0.73; 95% CI 0.61-0.88) 1
- The combined outcome of cardiovascular death or heart failure hospitalization was reduced by 17% (HR 0.83; 95% CI 0.73-0.95) 1
Kidney Protection:
- Composite kidney events (sustained 40% decline in kidney function, end-stage kidney disease, or kidney death) were reduced by 47% (HR 0.53; 95% CI 0.43-0.66) 1
Cardiovascular Events:
- Major adverse cardiovascular events (heart attack, stroke, cardiovascular death) showed no significant reduction (HR 0.93; 95% CI 0.84-1.03) 1
- All-cause mortality was not significantly reduced (HR 0.93; 95% CI 0.82-1.04) 1
Who Benefits Most
Patients with prior heart attack showed the greatest benefit:
- In the 3,584 patients with previous myocardial infarction, dapagliflozin reduced major cardiovascular events by 16% with an absolute risk reduction of 2.6% (15.2% vs 17.8%; HR 0.84; 95% CI 0.72-0.99) 4
- Benefits appeared greatest within 2 years after the most recent heart attack 4
Benefits were consistent regardless of:
- Baseline blood pressure levels—even normotensive patients benefited (HR 0.66 for heart failure hospitalization) 2
- Baseline HbA1c levels—benefits occurred even in patients with HbA1c <7% 3
- Kidney function—benefits extended to patients with eGFR as low as 25 mL/min/1.73 m² 5
Safety Profile
Common side effects to monitor:
- Genital yeast infections (approximately 6% vs 1% with placebo) 5
- Urinary tract infections 5
- Volume depletion, particularly in elderly patients or those on diuretics 6
Rare but serious risks:
- Euglycemic diabetic ketoacidosis (can occur even with normal blood glucose) 5
- Fournier's gangrene (necrotizing infection of the perineum) 5
Practical Implementation for Your Patient
Dosing:
- Fixed dose of 10 mg once daily—no titration required 5
- Can be initiated if eGFR ≥25 mL/min/1.73 m² for cardiovascular/kidney protection 5
- For glycemic control alone, only initiate if eGFR ≥45 mL/min/1.73 m² 5
Before starting, ensure:
- Volume status is adequate—correct any dehydration first 5
- Consider reducing diuretic doses to prevent excessive volume depletion 5
- Patient education about sick day rules (hold during acute illness with reduced oral intake) 5
Important contraindications:
- Withhold at least 3 days before major surgery or prolonged fasting 5
- Hold during acute illness with fever, vomiting, or diarrhea 5
Clinical Bottom Line
For your hospitalized patient with type 2 diabetes and cardiovascular disease or high cardiovascular risk, dapagliflozin provides substantial protection against heart failure hospitalization and kidney disease progression, with benefits independent of blood sugar control. The medication is particularly valuable if the patient has a history of heart attack, existing kidney disease with albuminuria, or heart failure. 1, 4