What is the difference between alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin?📊📊📊

Dipeptidyl peptidase-4 (DPP-4) inhibitor is a new type of oral hypoglycemic drug with the fastest growing clinical use recently. Alogliptin, linagliptin, saxagliptin, sitagliptin and vildagliptin all belong to this class of drugs, but what exactly is the difference between them?

What is the mechanism of action of DPP-4 inhibitors?

Intestinal cells are stimulated by food (especially carbohydrates) to secrete hormones (such as GIP and GLP-1) that increase insulin secretion. And 70 to 80% of the incretin activity is produced by GLP-1.

DPP-4 in the human body can easily degrade GLP-1. It results in a half-life of GLP-1 in plasma of less than two minutes. Concentrations of endogenous GLP-1 are elevated two to threefold by the efficacy of DPP-4 inhibitors in inhibiting DPP-4. The effects of promoting insulin secretion and inhibiting glucagon secretion of GLP-1 are glucose concentration-dependent. Therefore, DPP-4 inhibitors do not increase the risk of hypoglycemia and are therefore suitable for use in the elderly.

What is the difference in chemical structure between DPP-4 inhibitors?

Alogliptin

Linagliptin

Saxagliptin

Sitagliptin

Vildagliptin

What is the difference between the dosage of DPP-4 inhibitors?

1. Alogliptin: It is a DPP-4 competitive inhibitor. It binds non-covalently to the active site of DPP-4. Therefore, its half-life is relatively long, up to 21 hours. Alogliptin is taken once a day, 25 mg each time.
2. Linagliptin: It is a DPP-4 competitive inhibitor. It binds non-covalently to the active site of DPP-4. Therefore, its half-life is 12 hours. Linagliptin is taken once a day, 5 mg each time.
3. Saxagliptin: It binds covalently to the active site of DPP-4. Therefore, its dissociation and association will be slower. This makes its half-life only 2.5 hours, but its hypoglycemic effect lasts longer. Saxagliptin is taken once a day, 5 mg each time.
4. Sitagliptin: It is a DPP-4 competitive inhibitor. It binds non-covalently to the active site of DPP-4. Therefore, its half-life is about 12 hours. Sitagliptin is taken once a day, 100 mg each time.
5. Vildagliptin: It is also covalently bound to the active site of DPP-4. Its half-life is 3 hours. Vildagliptin is taken twice a day, 50 mg each time.

Food does not affect the absorption of the above DPP-4 inhibitors.

Precautions for use in patients with renal insufficiency.

1. Alogliptin: It is rarely metabolized in the body and its metabolites are also active. Its bioavailability can reach 100%. It rarely interacts with other medicines. About 76% of alogliptin is excreted through the kidneys. Therefore, its dosage should be adjusted when it is used in patients with renal insufficiency.
2. Linagliptin: It is rarely metabolized in the body. Its metabolites are inactive. Its bioavailability is about 30%. It rarely interacts with other medicines. Less than 5% of the administered dose of linagliptin is excreted by the kidneys. Therefore, it does not require dose adjustment when used in patients with renal insufficiency.
3. Saxagliptin: It is metabolized by CYP3A4/5. Its metabolites are active. Its bioavailability is about 67%. It rarely interacts with other medicines. Its usual dose is 5 mg once a day. However, when it is co-administered with potent CYP3A4/5 drugs such as itraconazole, clarithromycin and atazanavir, the dose of saxagliptin should not exceed 2.5 mg per day. About 75% of saxagliptin is excreted through the kidneys. Therefore, its dosage should be adjusted when it is used in patients with renal insufficiency.
4. Sitagliptin: It is rarely metabolized in the body. Its metabolites are inactive. Its bioavailability is about 87%. It rarely interacts with other medicines. About 79% of sitagliptin is excreted by the kidneys. Therefore, its dosage should be adjusted when it is used in patients with renal insufficiency.
5. Vildagliptin: It is not metabolized by CYP enzymes, but inactivated by hydrolysis. Its bioavailability is about 85%. It is less likely to interact with other drugs. About 85% of vildagliptin is excreted through the kidneys. Therefore, its dosage should be adjusted when it is used in patients with renal insufficiency.

What are the common adverse reactions of DPP-4 inhibitors?

It is possible that DPP-4 inhibitors increase GLP-1 levels. This can be associated with delayed gastric emptying and appetite suppression. Therefore, DPP-4 inhibitors can cause stomach upset. Their main adverse reactions are upper respiratory tract infection, nasopharyngitis and headache. Less common adverse reactions are hypersensitivity reactions and angioedema. 

In addition, alogliptin and saxagliptin have the potential to increase the risk of heart failure hospitalization events. Therefore, when a patient has risk factors for heart failure, the patient should be observed for symptoms and signs of heart failure during treatment.