糖尿病 (DPP4I / SGLT2I) Type 2 diabetes mellitus

Antidiabetic Agent, Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitor; Dipeptidyl Peptidase 4 (DPP-4) Inhibitor

1. Dapagliflozin
Duration: Following discontinuation, urinary glucose excretion returns to baseline within ~3 days for the 10 mg dose.
Protein binding: ~91%.
Metabolism: Primarily mediated by UGT1A9 to an inactive metabolite (dapagliflozin 3-O-glucuronide); CYP-mediated metabolism (minor).
Bioavailability: 78%.
Half-life elimination: ~12.9 hours.
Time to peak, plasma: 2 hours.
Excretion: Urine (75%; <2% as parent drug); feces (21%; ~15% as parent drug).
2. Saxagliptin
Duration: 24 hours
Protein binding: Negligible
Metabolism: Hepatic via CYP3A4/5 to 5-hydroxy saxagliptin (active; ~50% potency of the parent compound)
Half-life elimination: Saxagliptin: 2.5 hours; 5-hydroxy saxagliptin: 3.1 hours
Time to peak, plasma: 2 hours
Excretion: Urine (75%, 24% of the total dose as saxagliptin, 36% of the total dose as 5-hydroxy saxagliptin); feces (22%)

Serious hypersensitivity (eg, anaphylactic reactions, angioedema, exfoliative skin conditions) to dapagliflozin, saxagliptin, or any component of the formulation; moderate to severe renal impairment (eGFR <45 mL/minute/1.73 m2), end-stage renal disease, or patients on dialysis.

Not recommended during the second or third trimesters of pregnancy.

It is not known if dapagliflozin or saxagliptin are present in breast milk. Due to the potential for adverse events in a breastfed infant, breastfeeding is not recommended by the manufacturer.

>10%: Respiratory: Upper respiratory tract infection (14%)
1% to 10%:
Cardiovascular: Headache (4%)
Endocrine & metabolic: Dyslipidemia (5%), hypoglycemia (1%)
Gastrointestinal: Diarrhea (4%)
Genitourinary: Urinary tract infection (6%; mostly reported in females)
Infection: Vulvovaginal candidiasis (3%)
Neuromuscular & skeletal: Back pain (3%), arthralgia (2%)

Initial: Dapagliflozin 5 mg/saxagliptin 5 mg once daily in patients not already taking dapagliflozin; may increase to dapagliflozin 10 mg/saxagliptin 5 mg once daily in patients currently tolerating dapagliflozin 5 mg/saxagliptin 5 mg who require additional glycemic control.

1. eGFR ≥45 mL/min/1.73 m2: No dosage adjustment necessary.
2. eGFR <45 mL/minute/1.73 m2, ESRD or Hemodialysis: Use is contraindicated.

No dosage adjustment necessary; use with caution in severe impairment (has not been studied)