Is it okay to give dapagliflozin (Forxiga) to a non-diabetic patient with a history of gestational diabetes?

Dapagliflozin Use in Non-Diabetic Patients with History of Gestational Diabetes

Yes, dapagliflozin can be safely prescribed to a non-diabetic patient with a history of gestational diabetes, provided there are appropriate cardiovascular or renal indications and the patient is not pregnant or breastfeeding.

Current Diabetes Status Assessment

Before prescribing dapagliflozin, you must first confirm the patient's current glycemic status, as women with prior gestational diabetes have substantially elevated risk for progression to type 2 diabetes:

• Screen for current diabetes or prediabetes using a 75-g oral glucose tolerance test with clinically appropriate non-pregnancy diagnostic criteria, as this should be performed at 4-12 weeks postpartum and repeated at least every 3 years thereafter 1
• If the patient has developed prediabetes, intensive lifestyle interventions or metformin are the recommended first-line preventive therapies, not dapagliflozin 1
• If the patient has progressed to type 2 diabetes, then dapagliflozin becomes an appropriate therapeutic option with standard indications 2, 3

Indications for Dapagliflozin in Non-Diabetic Patients

If the patient remains non-diabetic, dapagliflozin can still be prescribed for the following FDA-approved indications that do not require diabetes:

Heart Failure Indication

• Dapagliflozin 10 mg once daily is approved for symptomatic heart failure regardless of ejection fraction (HFrEF, HFmrEF, or HFpEF) and independent of diabetes status 2, 4
• The DAPA-HF trial demonstrated a 26% reduction in cardiovascular death or heart failure hospitalization (HR 0.74,95% CI 0.65-0.85) in patients with heart failure, with benefits observed in both diabetic and non-diabetic patients 2, 4
• Initiate if eGFR ≥20 mL/min/1.73 m² for heart failure indication 3

Chronic Kidney Disease Indication

• Dapagliflozin 10 mg once daily is approved for chronic kidney disease with eGFR ≥25 mL/min/1.73 m² and albuminuria (UACR ≥200 mg/g), regardless of diabetes status 2, 3
• The DAPA-CKD trial included 32.5% of patients without diabetes and demonstrated a 39% reduction in the composite of sustained eGFR decline, end-stage kidney disease, or renal/cardiovascular death (HR 0.61,95% CI 0.51-0.72) 2, 3

Absolute Contraindications

Do not prescribe dapagliflozin if:

• The patient is pregnant or planning pregnancy - dapagliflozin crosses the placental barrier with fetal-to-maternal concentration ratios reaching 0.67 ± 0.05, and it interferes with placental leptin production 5
• The patient is breastfeeding - safety data are lacking 3
• eGFR <20 mL/min/1.73 m² for heart failure indication or eGFR <25 mL/min/1.73 m² for CKD indication 3
• The patient is on dialysis 3

Special Considerations for Women with Prior Gestational Diabetes

Evidence Supporting Use in This Population

A randomized trial specifically evaluated dapagliflozin in overweight women with recent gestational diabetes (within 12 months postpartum) and found:

• Dapagliflozin-metformin combination produced significant reductions in weight, waist circumference, and waist-to-height ratio compared to metformin alone 6
• Improved glycemia and insulin sensitivity were observed with combination therapy 6
• Cardiovascular benefits included increased HDL, reduced triglycerides, and improved glucose excursion 6
• This represents the only published trial examining SGLT2 inhibitors in this specific population 6

Clinical Decision Algorithm

For a non-diabetic patient with prior gestational diabetes:

1. Confirm non-diabetic status with 75-g OGTT if not done within the past year 1
2. Assess for cardiovascular or renal indications:
   • Check for symptomatic heart failure (any ejection fraction) 2, 4
   • Measure eGFR and urine albumin-to-creatinine ratio 2, 3
   • If UACR ≥200 mg/g and eGFR ≥25 mL/min/1.73 m², CKD indication exists 2, 3
3. If no cardiovascular/renal indication exists, dapagliflozin is not appropriate - instead recommend intensive lifestyle modification or metformin if prediabetes develops 1
4. If cardiovascular/renal indication exists, initiate dapagliflozin 10 mg once daily 2, 3

Safety Monitoring

When prescribing dapagliflozin to this population:

• Assess volume status before initiation and consider reducing concurrent diuretic doses 3
• Monitor for genital mycotic infections, which occur in approximately 6% of patients on SGLT2 inhibitors 3
• Educate about euglycemic diabetic ketoacidosis and instruct to withhold during acute illness with reduced oral intake, fever, vomiting, or diarrhea 3
• Withhold at least 3 days before major surgery or procedures requiring prolonged fasting 3
• Recheck eGFR within 1-2 weeks after initiation, as a transient dip of 3-5 mL/min/1.73 m² is expected 3

Common Pitfall to Avoid

Do not prescribe dapagliflozin solely for "diabetes prevention" in non-diabetic patients with prior gestational diabetes - this is not an approved indication, and lifestyle interventions or metformin are the evidence-based preventive strategies for prediabetes in this population 1. Dapagliflozin should only be prescribed when specific cardiovascular or renal indications exist, at which point the patient's diabetes status becomes irrelevant to the prescribing decision 2, 3, 4.