Alogliptin, saxagliptin, and sitagliptin (DPP-4 inhibitors) differ from pioglitazone in their effect on cardiovascular outcomes in CVOT trials. Which statement accurately reflects this difference?

• A DPP-4 inhibitors reduce heart failure hospitalisation, while pioglitazone has neutral effect
• B Saxagliptin in the SAVOR-TIMI trial increased heart failure hospitalisation by 27%; pioglitazone also increases heart failure risk due to fluid retention ✓
• C DPP-4 inhibitors reduce MACE events to a greater degree than pioglitazone
• D Pioglitazone increases bladder cancer risk but reduces heart failure risk; DPP-4 inhibitors have no bladder cancer association

Explanation

In the SAVOR-TIMI 53 trial, saxagliptin was associated with a significant 27% increase in heart failure hospitalisation compared to placebo, despite not increasing MACE. Alogliptin (EXAMINE trial) showed a numerically similar trend. The exact mechanism may involve DPP-4 inhibition affecting stromal cell-derived factor (SDF-1) and natriuretic peptide processing. Pioglitazone also increases heart failure risk and causes oedema/fluid retention via PPAR-gamma mediated sodium reabsorption in the distal nephron. Pioglitazone is contraindicated in heart failure. The statement about pioglitazone reducing heart failure is incorrect — it increases this risk.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.