Endocrinology · USMLE Step 1 and Step 2

DPP-4 Inhibitors song

DPP-4 Inhibitors - Mechanism & Safety, as a song. Hear the short teaser here. The full song is on YouTube and Spotify.

DPP-4 Inhibitors

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Key points in this song10

DPP-4 inhibitors (gliptins: sitagliptin, saxagliptin, alogliptin, linagliptin) work by blocking dipeptidyl peptidase-4, the enzyme that degrades GLP-1 and GIP, thereby increasing incretin levels and stimulating glucose-dependent insulin secretion.
Because insulin release is glucose-dependent, DPP-4 inhibitors carry a low risk of hypoglycemia when used as monotherapy.
DPP-4 inhibitors are weight-neutral, distinguishing them from GLP-1 agonists (weight loss) and sulfonylureas or insulin (weight gain).
Saxagliptin and alogliptin are associated with increased risk of heart failure hospitalization; they should be avoided in patients with pre-existing heart failure with reduced ejection fraction.
A classic adverse effect is nasopharyngitis and upper respiratory tract infections due to DPP-4's role in immune cell regulation.
DPP-4 inhibitors are associated with rare but serious immune-mediated bullous pemphigoid, a skin finding to recognize on USMLE vignettes.
Linagliptin is the only DPP-4 inhibitor eliminated primarily via the biliary/fecal route, making it safe in patients with chronic kidney disease without dose adjustment.
All other gliptins (sitagliptin, saxagliptin, alogliptin) require renal dose adjustment due to renal excretion.
DPP-4 inhibitors can rarely cause acute pancreatitis; they should be discontinued if pancreatitis is suspected.
Unlike SGLT-2 inhibitors and GLP-1 agonists, DPP-4 inhibitors have not demonstrated significant cardiovascular mortality benefit in major outcome trials.