Let's talk about hypoglycemic drugs.
DPP-4 inhibitors.
In the previous article, the mechanism of action of siglitazide sodium was briefly explained (in detail, the hypoglycemic drug - siglitazide sodium). In a phase III clinical study of sitaglitata sodium, which was compared to sitagliptin, the study showed that siglitat sodium significantly reduced HbA1C and was not inferior to the sitagliptin group.
Figure 1Both sitaglitat sodium and sitagliptin significantly reduced HbA1C
So what is sitagliptin?This article will briefly introduce this.
DPP-4 inhibitors.
Sitagliptin, the first dipeptidyl peptidase-4 inhibitor (DPP-4I), was developed by Merck & Co., and approved by the FDA in October 2006 for hypoglycemic drugs for type 2 diabetes by increasing the secretion of incretin in the body. Since then, other DPP-4I have been developed one after another, such as vildagliptin, saxagliptin, linagliptin, alogliptin, ticagliptin, etc.
Hypoglycemic mechanisms. There are two main types of hormones that regulate blood sugar: insulin-based hypoglycemic hormones, and glucagon-based glycemic hormones. For normal people, the intestines secrete incretin after eating, especially glucagon-like peptide-1 (GLP-1), active GLP-1 can induce insulin secretion, inhibit glucagon secretion, and can also suppress appetite, so that blood sugar can be maintained in a steady state and produce a feeling of satiety.
However, the half-life of active GLP-1 in the blood is only about 1 minute, and the reason why the half-life of active GLP-1 is short is mainly because it is easily degraded by DPP-4 enzymes.
Figure 2Metabolism and role of GLP-1.
Natural GLP-1 cannot be directly used in diabetes, so prolonging the life and effect of active GLP-1 in the body has become the direction of type 2 diabetes.
Based on this, inhibiting the DPP-4 enzyme to reduce the active GLP-1 degradation or enhance the activity of GLP-1 can play a role in lowering blood glucose. It is also the principle of action of DPP-4 inhibitors and GLP-1 receptor agonists.
Figure 3DPP-4I and GLP-1RA mechanisms.
Different DPP-4I usages.
Summary. Although both sitagliptin and sitaglitata sodium have "sitaglip", they are not the same kind of drugs. DPP-4I, represented by sitagliptin, does not have high requirements for liver and kidney function, and has a small risk of hypoglycemia, so it can be combined with hypoglycemic drugs other than GLP-1RA. However, its hypoglycemic magnitude is not too large, and the reduction of glycosylated hemoglobin is about 04%-1.0%。Compared with SGLT-2I and GLP-1RA, there is no clear cardiorenal benefit, and there is no obvious weight loss effect, so the current clinical application is somewhat limited.