What is the indication for dapagliflozin in adults with type 2 diabetes and a history of cardiovascular disease or kidney disease?

What is Dapagliflozin For?

Dapagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor indicated for reducing cardiovascular death, heart failure hospitalization, and kidney disease progression in adults with type 2 diabetes and established cardiovascular or kidney disease, as well as for treating heart failure and chronic kidney disease regardless of diabetes status. 1, 2

Primary Indications

Cardiovascular Protection in Type 2 Diabetes

• Dapagliflozin reduces cardiovascular death or heart failure hospitalization by 17-29% in patients with type 2 diabetes and established cardiovascular disease or multiple cardiovascular risk factors. 1, 3
• The medication prevents incident heart failure, with a 17% reduction in heart failure hospitalization in patients without prior heart failure. 2
• These cardiovascular benefits occur independently of baseline HbA1c levels or glycemic control needs. 3

Kidney Disease Protection

• Dapagliflozin provides robust kidney protection by reducing the composite outcome of sustained eGFR decline ≥50%, end-stage kidney disease, or renal/cardiovascular death by 39% (HR 0.61,95% CI 0.51-0.72) in patients with chronic kidney disease. 1, 3
• The renal-specific composite outcome (sustained eGFR decline ≥50%, end-stage kidney disease, or renal death) is reduced by 44% (HR 0.56,95% CI 0.45-0.68). 1, 3
• These kidney protective effects are independent of diabetes status—benefits are consistent in patients with and without type 2 diabetes. 4, 5
• Dapagliflozin slows the rate of eGFR decline and reduces progression to end-stage renal disease. 1, 2

Heart Failure Treatment

• Dapagliflozin 10 mg once daily is indicated for heart failure with reduced ejection fraction (HFrEF), reducing cardiovascular death or worsening heart failure by 26% (HR 0.74,95% CI 0.65-0.85). 2
• The medication also benefits heart failure with preserved ejection fraction (HFpEF), reducing worsening heart failure or cardiovascular death by 18% (HR 0.82,95% CI 0.73-0.92). 2
• These heart failure benefits occur regardless of diabetes status. 1

Glycemic Control

• Dapagliflozin improves glycemic control in adults with type 2 diabetes as an adjunct to diet and exercise, though this is considered a secondary benefit compared to its cardiovascular and renal protective effects. 1, 3
• The glucose-lowering efficacy decreases significantly when eGFR falls below 45 mL/min/1.73 m², but cardiovascular and renal benefits are preserved at lower eGFR levels. 2

Dosing and Initiation Criteria

Standard Dosing

• The fixed dose is 10 mg orally once daily for all indications—no titration is required or recommended. 1, 2

eGFR Thresholds for Initiation

• For cardiovascular and renal protection: initiate if eGFR ≥25 mL/min/1.73 m² (some guidelines support initiation at eGFR ≥20 mL/min/1.73 m²). 1, 2
• For glycemic control alone: initiate only if eGFR ≥45 mL/min/1.73 m², as glucose-lowering efficacy is minimal below this threshold. 2
• If eGFR falls below 25 mL/min/1.73 m² during treatment, dapagliflozin 10 mg daily may be continued until dialysis is required. 2

Patient Selection

• Strongest evidence supports use in patients with chronic kidney disease (UACR 200-5,000 mg/g and eGFR 25-75 mL/min/1.73 m²), with or without diabetes. 1, 3
• Patients with type 2 diabetes and established atherosclerotic cardiovascular disease or multiple cardiovascular risk factors. 1, 3
• Patients with heart failure (reduced or preserved ejection fraction), regardless of diabetes status. 2

Critical Safety Considerations and Contraindications

Absolute Contraindications

• History of serious hypersensitivity reaction to dapagliflozin. 1
• Patients on dialysis (though severe renal impairment down to eGFR 20-25 mL/min/1.73 m² is not a contraindication for cardiovascular/renal protection). 1

Important Precautions

• Withhold dapagliflozin at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis. 2
• Hold during acute illness, particularly with fever, vomiting, diarrhea, or reduced oral intake—this is critical "sick day management." 2
• Assess volume status before initiation and correct volume depletion if present, particularly in elderly patients, those on diuretics, or those with low systolic blood pressure. 1, 2
• Increased risk of genital mycotic infections (approximately 6% vs 1% with placebo)—counsel patients on hygiene measures. 1, 2
• Monitor for euglycemic diabetic ketoacidosis, which can occur even with normal blood glucose levels, especially during illness or with reduced insulin doses. 2

Medication Interactions

• When used with insulin or insulin secretagogues (sulfonylureas), hypoglycemia risk increases—consider reducing doses of these agents. 1
• Consider reducing concurrent diuretic doses when initiating dapagliflozin to prevent excessive volume depletion. 2

Key Clinical Advantages

Mortality Benefit

• Dapagliflozin reduces all-cause mortality by 31% (HR 0.69,95% CI 0.53-0.88) in patients with chronic kidney disease. 1, 3

Mechanism Independent of Glycemic Control

• The cardiovascular and renal protective effects are independent of glucose-lowering—benefits are consistent across all HbA1c levels and in patients without diabetes. 3, 4
• This distinguishes dapagliflozin from traditional diabetes medications like sulfonylureas, which provide only glycemic control without cardiovascular or renal protection. 2

Broad Applicability

• Benefits are consistent regardless of background glucose-lowering therapy, number of diabetes medications, or presence/absence of cardiovascular disease at baseline. 6, 5

Common Pitfalls to Avoid

• Do not discontinue dapagliflozin solely because eGFR falls below 45 mL/min/1.73 m²—cardiovascular and renal protective benefits persist even when glycemic efficacy is lost. 2
• Do not reduce the dose below 10 mg daily for any indication—all outcome trials used the fixed 10 mg dose. 2
• Do not continue dapagliflozin during acute illness without holding it—this significantly increases the risk of diabetic ketoacidosis and volume depletion. 2
• An initial eGFR dip of 3-5 mL/min/1.73 m² within the first 1-4 weeks is expected, transient, and reversible—do not discontinue the medication for this reason alone. 2