DPP-4 Inhibitors

Summary

DPP-4 inhibitors are a class of drugs recognizable by their -gliptin ending, including sitagliptin, linagliptin, and saxagliptin. These drugs are used to treat type 2 diabetes mellitus by lowering blood sugar levels. Inhibition of the DPP-4 enzyme has several downstream effects, including increasing GLP-1 levels, decreasing gastric emptying and increasing satiety. These drugs also stimulate glucose-dependent insulin release, and decrease glucagon release. Side effects of these drugs include an increased risk of developing urinary infections and upper respiratory infections. Notably, these drugs typically do not cause hypoglycemia, and usually have no effect on weight in patients.

Key Points

• DPP-4 Inhibitors
  • Drug Names
    • -gliptin
      • Linagliptin
      • Saxagliptin
      • Sitagliptin
      • Alogliptin
  • Mechanism
    • Inhibits DPP-4 (dipeptidyl peptidase)
      • Increases GLP-1 (glucagon-like peptide)
        • Dipeptidyl peptidase-4 (DPP-4) normally works to break down hormones like GLP-1
      • Decreased glucagon release
      • Decreased gastric emptying
      • Increased glucose-dependent insulin release
        • Do not cause hypoglycemia since the increase is glucose dependent
        • Think: uses indirect machinery (does not directly act on beta cells, so body’s homeostatic effects remain intact)
  • Clinical Use
    • Treats diabetes mellitus
  • Side Effects
    • (Upper) Respiratory infections
      • Small risk in nasopharyngitis and other viral infections of the upper respiratory tract
    • Urinary infections
      • Small increase in UTI risk
    • Weight neutral
      • No effect on weight
    • Increased satiety
      • Often a desirable side effect
    • Does not cause hypoglycemia
      • Since increase in insulin is glucose-dependent, the insulin release is stopped when glucose levels fall too low