Pharmacology · DPP-4 inhibitors (gliptins)
Saxagliptin !
A DPP-4 inhibitor metabolized by CYP3A4. It raised heart failure hospitalizations in a large trial, so it is avoided in heart failure.
Updated 2026-11-01
The figure shows saxagliptin (BMS-477118) in the active site of human DPP-4, where it binds the catalytic serine covalently and reversibly.
Mechanism of action
Saxagliptin is a cyanopyrrolidine that forms a reversible covalent bond with the catalytic serine of DPP-4. The enzyme stays blocked for long, active GLP-1 and GIP rise after meals, and insulin increases and glucagon falls when glucose is high. Its active metabolite also inhibits DPP-4.
- 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, with or without food.
- Metabolism
- By CYP3A4/5 in the liver to an active metabolite.
- Elimination
- Kidney and liver; the dose is lowered in moderate to severe kidney impairment.
Indications
- Type 2 diabetes, with diet and exercise Type 2 diabetes mellitus →
Adverse effects
Common
- Upper respiratory and urinary tract infections, headache
- Hypoglycemia with insulin or a sulfonylurea
Contraindications
- Serious hypersensitivity to saxagliptin
- Not for type 1 diabetes or ketoacidosis
Key interactions
- Strong CYP3A4/5 inhibitors (ketoconazole, clarithromycin, ritonavir)
- Raise saxagliptin levels; the dose is limited.
- Insulin or sulfonylureas
- Higher risk of hypoglycemia.
What is monitored
- Kidney function
- Signs of heart failure (weight gain, edema, breathlessness)
- HbA1c
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.
- Ask about new antifungal, antibiotic or HIV drugs (CYP3A4 inhibitors).
Pregnancy and breastfeeding
Data in pregnancy are limited; insulin is the usual choice.
Test yourself
Think of the answer, then tap the question to see it.
Which DPP-4 inhibitor is linked to more heart failure hospitalizations?
Saxagliptin, in a large cardiovascular outcomes trial.
Why does ketoconazole matter for saxagliptin?
It strongly inhibits CYP3A4, the enzyme that metabolizes saxagliptin, raising its levels.
How does saxagliptin bind DPP-4?
Through a reversible covalent bond with the catalytic serine of the enzyme.
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: Saxagliptin: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); DailyMed - SAXAGLIPTIN tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); Crystal structure of human DPP-IV in complex with (1S,3S, 5S)-2-[(2S)-2-AMINO-2-(3-HYDROXYTRICYCLO[3.3.1.13,7]DEC-1- YL)ACETYL]-2-AZABICYCLO[3.1.0]HEXANE-3-CARBONITRILE (CAS), (1S,3S,5S)-2-((2S)-2-AMINO-2-(3-HYDROXYADAMANTAN-1- YL)ACETYL)-2-AZABICYCLO[3.1.0]HEXANE-3-CARBONITRILE (IUPAC), OR BMS-477118 (RCSB Protein Data Bank, 2008); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.