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# DPP-4 inhibitors (gliptins)

Oral drugs that stop the breakdown of the body's own gut hormones (incretins), so insulin rises after meals. Gentle and weight-neutral.

Updated 2026-11-01

## What they are

Inhibitors of the enzyme dipeptidyl peptidase-4. Used in type 2 diabetes, usually added to metformin.

## Mechanism of action

DPP-4 is a serine protease on cell surfaces and in plasma that inactivates GLP-1 and GIP within minutes by cutting two amino acids off their N-terminus. Gliptins block it, so active incretin levels rise after meals; insulin release increases and glucagon falls, both in a glucose-dependent way.

Target: Dipeptidyl peptidase-4 (DPP4, CD26)

## Key points

- Low risk of hypoglycemia and no weight change; modest glucose lowering.
- Acute pancreatitis has been reported; severe joint pain and bullous pemphigoid are class warnings.
- Saxagliptin raised heart failure hospitalizations in a large trial.
- Most are cleared by the kidney and need adjustment; linagliptin is mainly excreted in bile and feces.
- Do not combine with a GLP-1 agonist: they act on the same axis.

## Drugs in this class

- [**Sitagliptin** The first DPP-4 inhibitor: an oral tablet that protects the body's own incretins, with low hypoglycemia risk and no… Dipeptidyl peptidase-4 (DPP-4)](https://durgical.com/en/pharmacology/sitagliptin/)
- [**Linagliptin** A DPP-4 inhibitor cleared mainly through bile, so it needs no kidney adjustment. Low hypoglycemia risk, no weight… Dipeptidyl peptidase-4 (DPP-4)](https://durgical.com/en/pharmacology/linagliptin/)
- [**Saxagliptin** A DPP-4 inhibitor metabolized by CYP3A4. It raised heart failure hospitalizations in a large trial, so it is avoided… Dipeptidyl peptidase-4 (DPP-4)](https://durgical.com/en/pharmacology/saxagliptin/)
- [**Vildagliptin** A DPP-4 inhibitor used in Europe and other regions, not in the US. It binds the enzyme covalently and is cleared… Dipeptidyl peptidase-4 (DPP-4)](https://durgical.com/en/pharmacology/vildagliptin/)

## Others in the class

- alogliptin

## Test yourself

Think of the answer, then tap the question to see it.

## Which hormones does DPP-4 inactivate?

The incretins GLP-1 and GIP, by removing the first two amino acids from their N-terminal end.

## Which gliptin needs no kidney adjustment, and why?

Linagliptin, because it is eliminated mainly unchanged through bile and feces rather than urine.

## Why are DPP-4 inhibitors weight-neutral while GLP-1 agonists cause weight loss?

They only raise the body's own incretins to physiological levels, too low to slow the stomach or reduce appetite much.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [Sitagliptin: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a606023.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [DailyMed - SITAGLIPTIN tablet, film coated](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=58e23b30-451c-f451-e063-6394a90a35a7) (DailyMed (U.S. National Library of Medicine), 2026); [HUMAN DIPEPTIDYL PEPTIDASE IV IN COMPLEX WITH A BETA AMINO ACID INHIBITOR](https://www.rcsb.org/structure/1X70) (RCSB Protein Data Bank, 2005).

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Representative model, for educational purposes only.

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