What is the role of DPP-4 inhibitors in the treatment of diabetic nephropathy?

Updated: Oct 09, 2019
  • Author: Vecihi Batuman, MD, FASN; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
  • Print

The dipeptidyl peptidase (DPP)–4 inhibitors (ie, gliptins) are a new class of antidiabetic agents that can be used in type 2 diabetes. These agents include sitagliptin, saxagliptin, linagliptin, and alogliptin, and they decrease the breakdown of the incretin hormones such as glucagonlike peptide 1 (GLP-1). GLP-1 is secreted by the GI tract in response to food intake and leads to insulin secretion in a glucose-dependent manner, while also decreasing glucagon release. GLP-1 also slows gastric emptying.

Sitagliptin was the first available DPP-4 inhibitor. Approximately 80% of sitagliptin is cleared by the kidney; therefore, the standard dose of 100 mg daily should be reduced in patients with reduced glomerular filtration rates (GFRs). With an estimated GFR (eGFR) of 30 or greater to less than 50 mL/min/1.73 m2, the recommended dose is 50 mg once daily, and with an eGFR less than 30 mL/min/1.73 m2, a dose of 25 mg once daily is advised. [28]

The starting dose for saxagliptin is 2.5-5 mg daily in patients with an eGFR greater than 50 mL/min, but dose adjustment is recommended in patients with an eGFR of 50 mL/min/1.73 m2 or less to 2.5 mg daily.

Alogliptin also requires a dose reduction from 25 mg daily to 12.5 mg daily in patients with an eGFR of less than 60 mL/min/1.73 m2 and to 6.25 mg daily if the eGFR is less than 30 mL/min/1.73 m2.

In contrast, only the kidney clears a small amount of linagliptin; thus, no dose adjustment is necessary in patients with a reduced GFR. [29]

Did this answer your question?
Additional feedback? (Optional)
Thank you for your feedback!