Is dapagliflozin (Forxiga) effective for treating obesity?

Dapagliflozin for Obesity

Dapagliflozin is not FDA-approved for obesity treatment and should not be used as a primary obesity medication, but it does produce modest weight loss (2-3 kg) as a secondary benefit when used for its approved indications in patients with type 2 diabetes, heart failure, or chronic kidney disease. 1

FDA-Approved Indications and Weight Effects

Dapagliflozin is FDA-approved exclusively for:

• Type 2 diabetes mellitus management 1
• Heart failure (regardless of ejection fraction) 2, 3
• Chronic kidney disease 2

Weight loss is a consistent secondary effect but not the primary therapeutic target. In clinical trials for diabetes, dapagliflozin produced:

• Mean weight reduction of 2.0-3.3 kg compared to placebo over 24-52 weeks 1
• Relative weight loss of 1.9-2.4% consistently across all BMI categories 4
• Greater absolute weight loss in patients with higher BMI (up to 2.5 kg in those with BMI ≥40 kg/m²) 5

Current Guideline Recommendations for Obesity

The 2024 ADA Standards of Care explicitly outline FDA-approved obesity pharmacotherapy, which includes:

• GLP-1 receptor agonists (semaglutide 2.4 mg weekly, liraglutide)
• Combination agents (phentermine/topiramate, naltrexone/bupropion)
• Orlistat
• SGLT2 inhibitors like dapagliflozin are notably absent from this list 2

The guidelines specify that obesity medications should produce ≥5% weight loss after 3 months to justify continuation 2. Dapagliflozin typically produces only 2-3% weight loss, falling short of this efficacy threshold 1.

Clinical Context Where Weight Loss Occurs

In Patients with Type 2 Diabetes and Obesity

When dapagliflozin is used for glycemic control in obese patients with diabetes:

• Weight loss occurs through glucosuria (urinary glucose excretion of ~70-80g/day) 6
• Fat mass specifically decreases (mean 9.9 kg reduction when combined with carbohydrate restriction) 7
• No compensatory increase in appetite or decrease in energy expenditure 7

In Patients with Heart Failure and Obesity

In the DELIVER trial examining heart failure with preserved ejection fraction:

• Dapagliflozin reduced cardiovascular death or heart failure hospitalization consistently across all BMI categories (HR 0.72-0.89) 5
• Placebo-corrected weight loss at 12 months ranged from 0.65 kg (overweight) to 2.50 kg (Class III obesity) 5
• Patients with obesity derived greater symptom improvement (8.6-point KCCQ improvement in Class III obesity vs. 0.9 points in normal weight) 5

Mechanistic Considerations

Dapagliflozin's weight loss mechanism differs fundamentally from approved obesity medications:

• Caloric loss through glucosuria (not appetite suppression or absorption blockade) 6
• Mild diuretic effect contributing ~1 kg of initial weight loss 6
• Potential improvement in insulin sensitivity secondary to glucose reduction 6

The DECLARE-TIMI 58 trial demonstrated that while relative cardiovascular risk reductions were consistent across BMI categories, obese patients (BMI ≥30 kg/m²) had greater absolute risk reduction in heart failure hospitalization and atrial fibrillation (P for interaction 0.02 and 0.09, respectively) 4.

Practical Clinical Algorithm

For patients with obesity alone (no diabetes, heart failure, or CKD):

• Do not prescribe dapagliflozin
• Use FDA-approved obesity medications (GLP-1 RAs preferred for weight loss >10-15%) 2

For patients with obesity plus type 2 diabetes:

• Prioritize GLP-1 receptor agonists for dual glycemic and weight benefits 2
• Consider dapagliflozin if cardiovascular disease, heart failure, or CKD present (weight loss is a bonus, not the goal) 2
• If using dapagliflozin for cardiorenal protection, expect 2-3 kg weight loss as secondary benefit 1

For patients with obesity plus heart failure:

• Prescribe dapagliflozin 10 mg daily for heart failure management (Class I recommendation) 2, 3
• Expect modest weight loss (0.65-2.5 kg depending on baseline BMI) 5
• Greater symptom improvement occurs in patients with higher BMI 5

Important Caveats

• Dapagliflozin's 2-3% weight loss is insufficient to meet obesity treatment efficacy standards (≥5% at 3 months) 2, 1
• The medication carries risks of genital mycotic infections (1.5-1.7%), urinary tract infections (2.3-2.7%), and volume depletion 8
• Euglycemic ketoacidosis risk exists, particularly with carbohydrate restriction or fasting 2
• Cost considerations: dapagliflozin costs significantly more than established obesity medications without superior weight loss efficacy 2