Differential pharmacology and clinical utility of empagliflozin in type 2 diabetes

Figures & data

Table 1 Pharmacokinetic and pharmacodynamic characteristics of empagliflozin when given orally at clinically available doses of either 10 mg/d or 25 mg/d

Pharmacokinetics and pharmacodynamics of empagliflozin (10–25 mg/d)
High SGLT2 selectivity	IC50 of 3.1 nM
SGLT2:SGLT1 selectivity ratio	2,500:1
Time to peak absorption after oral intake	1.5–2.1 hours
Maximum plasma concentration	226–722 nmol/L
Area under concentration–time curve	1,550–6,180 nmol⋅h/L
Terminal elimination half-life	7.8–14.3 hours
Renal clearance over 72 hours	21.1–41.1 mL/min
Terminal elimination half-life with hepatic impairment (50 mg)	17.1–18.1 hours
Terminal elimination half-life with renal impairment (50 mg)	22.0–27.9 hours
Renal clearance over 72 hours with renal impairment (50 mg)	0.5–18.6 mL/min
Urinary glucose excretion over 24 hours	∼40–90 g/d

Note: Terminal elimination half-life with hepatic or renal impairment and renal clearance with renal impairment are shown for 50 mg/d, since those studies were done with only one dose.

Abbreviations: SGLT2, sodium glucose transporter-2; SGLT1, sodium glucose transporter-1; IC₅₀, half maximal inhibitory concentration.

Figure 1 A summary of the glycemic, cardiovascular, renal, and adverse effects of empagliflozin.

Abbreviations: GFR, glomerular filtration rate; HDL, high-density lipoprotein; LDL, low-density lipoprotein; UTI, urinary tract infection; BP, blood pressure; CHF, congestive heart failure.

Table 2 Clinical properties of empagliflozin when given orally at clinically available doses of either 10 mg/d or 25 mg/d

Clinical properties of empagliflozin (10–25 mg/d)
Decrease in HbA1c	∼−0.6%–0.9%
Decrease in fasting plasma glucose	∼−20 mg/dL to −35 mg/dL
Decrease in HbA1c with baseline A1c ≥8.5%	∼1.2%–1.4%
Decrease in HbA1c with baseline A1c ≥10%	∼3%
Decrease in HbA1c with stage 2 or 3 CKD	∼−0.4% to −0.6%
Decrease in body weight	∼2–3 kg
Decrease in fasting plasma glucose	∼20–30 mg/dL
Decrease in systolic blood pressure	∼3–7 mmHg
Decrease in diastolic blood pressure	∼1–3 mmHg
Decrease in waist circumference	∼1–1.5 cm
Decrease in uric acid	∼0.5–1 mg/dL
Decreased risk of death from cardiovascular cause	−38%
Decreased all-cause mortality	−32%
Decreased hospitalization for congestive heart failure	−35%
Decreased new onset or worsening of neuropathy	−39%
Hypoglycemia	∼3%–5%
Genital infections	∼3%–5%

Abbreviations: HbA1c, hemoglobin A1c; CKD, chronic kidney disease.