Pharmacology · DPP-4 inhibitors (gliptins)
Sitagliptin !
The first DPP-4 inhibitor: an oral tablet that protects the body's own incretins, with low hypoglycemia risk and no weight gain.
Updated 2026-11-01
The figure shows sitagliptin (labelled in the entry as a beta-amino acid inhibitor) in the active site of human DPP-4.
Mechanism of action
Sitagliptin is a competitive, reversible inhibitor of DPP-4. With the enzyme blocked, active GLP-1 and GIP rise after meals, insulin secretion increases and glucagon falls, only while glucose is high. The effect on HbA1c is moderate.
- Blocks the DPP-4 enzyme in plasma and on cells
- Active GLP-1 and GIP last longer after meals
- More insulin and less glucagon when glucose is high
- Glucose falls without weight change
Pharmacokinetics
- Absorption
- Oral, well absorbed.
- Metabolism
- Little metabolism.
- Elimination
- Mostly unchanged in urine, so the dose is lowered in kidney impairment.
- Half-life
- Allows once-daily use.
Indications
- Type 2 diabetes, with diet and exercise, alone or with metformin and other drugs Type 2 diabetes mellitus →
Adverse effects
Common
- Upper respiratory infection, sore throat, headache
- Hypoglycemia when combined with insulin or a sulfonylurea
Contraindications
- Hypersensitivity to sitagliptin (anaphylaxis, angioedema)
- Not for type 1 diabetes or ketoacidosis
Key interactions
- Insulin or sulfonylureas
- Higher risk of hypoglycemia.
- GLP-1 receptor agonists
- Not combined: same pathway, no extra benefit.
What is monitored
- Kidney function before starting and periodically
- HbA1c
- Symptoms of pancreatitis
Administration and safety
- Oral tablet, once a day, with or without food.
- Not given together with a GLP-1 receptor agonist.
Nursing care
- Before: kidney function, history of pancreatitis and heart failure.
- During: abdominal pain, skin blisters, joint pain, swelling or breathlessness.
- Capillary glucose when combined with insulin or a sulfonylurea.
Pregnancy and breastfeeding
Data in pregnancy are too limited to judge the risk; insulin is the usual choice.
Test yourself
Think of the answer, then tap the question to see it.
Why does sitagliptin need adjustment in kidney disease?
It is cleared mainly unchanged by the kidney, so levels rise when filtration falls.
Which skin disease is a class warning for DPP-4 inhibitors?
Bullous pemphigoid: tense blisters that may need hospital care; the drug is stopped.
Is weight gain expected with sitagliptin?
No. DPP-4 inhibitors are weight-neutral.
Related drugs
Related conditions
← Back to the class: DPP-4 inhibitors (gliptins)
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 (MedlinePlus (U.S. National Library of Medicine), 2026); DailyMed - SITAGLIPTIN tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); HUMAN DIPEPTIDYL PEPTIDASE IV IN COMPLEX WITH A BETA AMINO ACID INHIBITOR (RCSB Protein Data Bank, 2005); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.