Dipeptidyl peptidase-4 inhibitor
Inhibitors of dipeptidyl peptidase 4 are a class of oral hypoglycemics that block the enzyme dipeptidyl peptidase-4. They can be used to treat diabetes mellitus type 2.
The first agent of the class—sitagliptin—was approved for marketing by the US Food and Drug Administration in 2006.
Glucagon increases blood glucose levels, and DPP-4 inhibitors reduce glucagon and blood glucose levels. The mechanism of DPP-4 inhibitors is to increase incretin levels, which inhibit glucagon release, which in turn increases insulin secretion, decreases gastric emptying, and decreases blood glucose levels.
A 2018 meta-analysis found no favorable effect of DPP-4 inhibitors on all-cause mortality, cardiovascular mortality, myocardial infarction or stroke in patients with type 2 diabetes.
Examples
Drugs belonging to this class are:- Sitagliptin
- Vildagliptin
- Saxagliptin
- Linagliptin
- Gemigliptin
- Anagliptin
- Teneligliptin
- Alogliptin
- Trelagliptin
- Omarigliptin
- Evogliptin
- Gosogliptin
- Dutogliptin
- Neogliptin
- Retagliptin
- Denagliptin
- Cofrogliptin
- Fotagliptin
- Prusogliptin
- Cetagliptin
Adverse effects
In individuals already taking sulphonylureas, use of DPP-4-class medications concurrently increases their risk for low blood sugar events relative to those on sulphonylureas alone.Adverse effects include nasopharyngitis, headache, nausea, heart failure, hypersensitivity, and skin reactions.
In late August 2015, the US FDA issued a warning that drugs like sitagliptin, saxagliptin, linagliptin, alogliptin, and other DPP-4 inhibitors could cause joint pain that can be severe and disabling. However, studies assessing risk of rheumatoid arthritis among DPP-4 inhibitor users have been inconclusive. A 2014 review found that the use of saxagliptin and alogliptin increased individuals' risk of developing heart failure, leading the FDA to add warnings to the labels of these drugs in 2016. A 2018 meta-analysis indicated that the use of DPP-4 inhibitors was associated with a 58% increased risk of developing acute pancreatitis compared to placebo or no treatment. Additionally, a 2018 observational study suggested an elevated risk of developing inflammatory bowel disease, specifically ulcerative colitis, which peaked after three to four years of use and decreased after more than four years. Finally, a 2020 Cochrane systematic review found insufficient evidence to suggest that metformin monotherapy reduced all-cause mortality, serious adverse events, cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, or end-stage renal disease when compared to DPP-4 inhibitors for the treatment of type 2 diabetes.