Are pioglitazone and Farxiga (dapagliflozin) the same medication?

No, Pioglitazone and Farxiga (Dapagliflozin) Are Not the Same Medication

Pioglitazone and Farxiga (dapagliflozin) are completely different medications from distinct drug classes with different mechanisms of action, indications, and clinical effects. 1

Drug Class and Mechanism of Action

• Pioglitazone is a thiazolidinedione (TZD) that activates peroxisome proliferator-activated receptor γ (PPAR-γ), improving insulin sensitivity in skeletal muscle and adipose tissue while reducing hepatic glucose production 1

• Dapagliflozin (Farxiga) is a sodium-glucose co-transporter-2 (SGLT2) inhibitor that blocks renal glucose reabsorption in the proximal tubule, leading to urinary glucose excretion and sodium diuresis 2, 3

Clinical Indications

Pioglitazone Indications:

• Type 2 diabetes mellitus for glycemic control 1
• Nonalcoholic steatohepatitis (NASH) with or without diabetes—pioglitazone improves liver histology and resolves steatohepatitis 4

Dapagliflozin (Farxiga) Indications:

• Type 2 diabetes mellitus 2
• Chronic heart failure (both reduced and preserved ejection fraction) 2
• Chronic kidney disease with eGFR ≥20 mL/min/1.73 m² and albuminuria 2

Cardiovascular and Renal Effects

• Pioglitazone reduces cardiovascular events in patients with macrovascular disease and prevents progression from prediabetes to diabetes, but causes fluid retention and is contraindicated in NYHA class III or IV heart failure 1, 4

• Dapagliflozin reduces cardiovascular death or heart failure hospitalization by 26-29%, slows kidney disease progression by 39-44%, and reduces all-cause mortality by 31% 2

Side Effect Profiles

Pioglitazone:

• Weight gain (average 2.7%) 4
• Fluid retention and edema 1
• Possible increased bladder cancer risk 1
• Contraindicated in decompensated cirrhosis 4

Dapagliflozin:

• Genital mycotic infections (≈6% vs 1% placebo) 2
• Urinary tract infections 2, 3
• Volume depletion risk 2
• Euglycemic diabetic ketoacidosis (rare) 2
• Weight loss (not weight gain) 3

Renal Dosing Considerations

• Pioglitazone requires no dose adjustment for renal impairment and can be used in end-stage kidney disease 4

• Dapagliflozin should not be initiated for glycemic control if eGFR <45 mL/min/1.73 m², though it can be started at eGFR ≥25 mL/min/1.73 m² for cardiovascular/renal protection 4, 2

Combination Therapy

• Pioglitazone can be combined with SGLT2 inhibitors like dapagliflozin to prevent weight gain associated with pioglitazone while maintaining its metabolic benefits 4

• When used together, these medications provide complementary mechanisms—pioglitazone improves insulin sensitivity while dapagliflozin increases urinary glucose excretion independent of insulin action 3