saxagliptin
Brand: Onglyza
Prototype: sitagliptin
Drug Class: DPP-4 inhibitor
Drug Family: antidiabetic
Subclass: dipeptidyl peptidase-4 inhibitor
Organ Systems: endocrine
Mechanism of Action
Inhibits DPP-4 to prolong the action of endogenous incretin hormones GLP-1 and GIP, glucose-dependently increasing insulin secretion and decreasing glucagon, lowering postprandial and fasting glucose.
DPP-4 enzyme
Indications
- type 2 diabetes mellitus
Contraindications
- type 1 diabetes
- DKA
- avoid if history of heart failure or pancreatitis
Adverse Effects
Common
- upper respiratory infections
- nasopharyngitis
- urinary tract infections
Serious
- heart failure hospitalization (increased risk, SAVOR-TIMI trial)
- pancreatitis
- severe arthralgia
- hypersensitivity
- bullous pemphigoid
Pharmacokinetics (ADME)
| Absorption | oral bioavailability ~75% |
| Distribution | negligible protein binding |
| Metabolism | hepatic via CYP3A4/5 to active metabolite (5-hydroxy saxagliptin) |
| Excretion | renal (75%) and fecal (22%) |
| Half-life | 2.5 hours (saxagliptin); 3.1 hours (active metabolite) |
| Onset | rapid |
| Peak | 2 hours |
| Duration | 24 hours |
| Protein Binding | negligible |
| Vd | 2.6 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| strong CYP3A4 inhibitors (ketoconazole) | increase saxagliptin exposure 2.5-fold; reduce dose to 2.5 mg | major |
Nursing Considerations
- Reduce dose from 5 mg to 2.5 mg daily with strong CYP3A4 inhibitors or renal impairment (eGFR <45 mL/min).
- Saxagliptin is the DPP-4 inhibitor with the strongest signal for increased heart failure hospitalization (SAVOR-TIMI); avoid in patients with existing heart failure.
- Monitor for pancreatitis symptoms (severe, persistent abdominal pain); discontinue if pancreatitis suspected.
- Educate patients that saxagliptin has a low hypoglycemia risk as monotherapy due to glucose-dependent action.
Clinical Pearls
- Among DPP-4 inhibitors, only saxagliptin showed an increased rate of heart failure hospitalization (27% relative increase) in the SAVOR-TIMI trial; this distinguishes it from sitagliptin and linagliptin.
- Despite its cardiovascular signal, saxagliptin remains used clinically, particularly when it's already part of an established regimen.
Safety Profile
Pregnancy avoid
Lactation insufficient-data
Renal Adjustment Required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.