What are DPP4 inhibitors and how do they work?

Members of this family : Sitagliptin, Vildagliptin, Saxagliptin. 

Background

The DPP4 enzyme was first identified in 1966. Its role in blood glucose control was recognized in the late 1980s when researchers discovered its involvement in the breakdown of the GLP-1 hormone.

Enzymes are substances found in our bodies; they help speed up various processes. They can build some substances and break down other substances. Each enzyme works on a specific substance, like a lock and key. The enzyme recognises a specific place on the substance it acts on, where it binds to produce its effect.

The DPP4 enzyme causes the rapid breakdown of incretin hormones GLP-1 and GIP. It became clear to researchers that if they could block the effects of the enzyme, they could extend the effect of both incretin hormones.

Researchers in the 1990s, where able to show that in animals studies certain substances were able to reduce the amount of enzyme in the body, thus increasing the effect of the GLP-1 hormone.

Edwin Villhauer a researcher at Novartis encouraged by these findings studied a lot of these inhibitor substances in a bid to understand the specific place where the enzyme binds. From his work he was able to design Vildagliptin. Vildagliptin went through a series of safety studies laying a foundation for other DPP4 inhibitors. The first DPP4 inhibitor for use in Type 2 diabetes was approved in 2006.

How do DPP 4 inhibitors work?

DPP 4 inhibitors produce their blood glucose lowering effect by preventing the DPP4 enzyme from breaking down incretin hormones GLP-1 and GIP. This increases active incretin hormones, which boost insulin release from the pancreas and reduce glucagon secretion, thereby lowering blood glucose levels.

Factors to consider when using DPP 4 inhibitors.

Risk of hypoglycaemia.

DPP4 inhibitors have a low risk of hypoglycaemia. However, combining them with other glucose-lowering medications increases this risk.

Glycaemic control

DPP-4 inhibitors reduce HbA1c by 0.5% to 0.8% when used alone.

Effect on weight

DDP-4 inhibitors are weight-neutral; they do not cause weight loss or weight gain.

Benefits to heart and kidneys

DPP4 inhibitors have not been shown to have any protective heart and kidney benefits.

Cost

DPP4 inhibitors are less expensive compared to other newer classes of glucose-lowering medications.

Side Effects

Most common side effects associated with DPP4 inhibitors include chest infections, stuffy and runny nose, headache, and sore throat.

Less common side effects include swelling of the pancreas (pancreatitis), joint pain and skin rashes.