1% 12.2%
Male genital mycotic infections‡ 0.4% 3.7% 4.2%
Urinary tract infections§ 3.9% 4.0% 4.1%
Headache 2.3% 3.5% 2.9%
Vaginal pruritus¶ 0.4% 2.8% 2.4%
Increased urination# 1.0% 2.7% 2.4%
Nasopharyngitis 2.3% 2.5% 2.0%
Back pain 2.3% 1.7% 2.5%
Weight decreased 1.0% 1.2% 2.4%
ThirstÞ 0.6% 2.7% 1.4%
Volume Depletion
Ertugliflozin causes an osmotic diuresis, which may lead to intravascular volume contraction and adverse reactions related to volume depletion, particularly in patients with impaired renal function (eGFR less than 60 mL/min/1.73 m2). In patients with moderate renal impairment, adverse reactions related to volume depletion (e.g., dehydration, dizziness postural, presyncope, syncope, hypotension, and orthostatic hypotension) were reported in 0%, 4.4%, and 1.9% of patients treated with placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg, respectively. Ertugliflozin may also increase the risk of hypotension in other patients at risk for volume contraction [see Use in Specific Populations (8.5, 8.6)].
Ketoacidosis
Across the clinical program, ketoacidosis was identified in 3 of 3,409 (0.1%) ertugliflozin-treated patients and 0.0% of comparator-treated patients [see Warnings and Precautions (5.3)].
Impairment in Renal Function
Treatment with ertugliflozin was associated with increases in serum creatinine and decreases in eGFR (see Table 2). Patients with moderate renal impairment at baseline had larger mean changes. In a study in patients with moderate renal impairment, these abnormal laboratory findings were observed to reverse after treatment discontinuation [see Use in Specific Populations (8.5, 8.6)].
Table 2: Changes from Baseline in Serum Creatinine and eGFR in the Pool of Three 26-Week Placebo-Controlled Studies and a 26-Week Moderate Renal Impairment Study in Patients with Type 2 Diabetes Mellitus
Pool of 26-Week Placebo-Controlled Studies
Placebo
N = 515 Ertugliflozin 5 mg
N = 519 Ertugliflozin 15 mg
N = 510
Baseline Mean Creatinine (mg/dL) 0.83 0.82 0.82
eGFR (mL/min/1.73 m2) 89.5 88.2 89.0
Week 6 Change Creatinine (mg/dL) 0.00 0.03 0.03
eGFR (mL/min/1.73 m2) -0.3 -2.7 -3.1
Week 26 Change Creatinine (mg/dL) -0.01 0.00 0.01
eGFR (mL/min/1.73 m2) 0.7 0.5 -0.6
Moderate Renal Impairment Study
Placebo
N = 154 Ertugliflozin 5 mg
N = 154 Ertugliflozin 15 mg
N = 154
Baseline Creatinine (mg/dL) 1.39 1.38 1.37
eGFR (mL/min/1.73 m2) 46.0 46.8 46.9
Week 6 Change Creatinine (mg/dL) -0.02 0.11 0.12
eGFR (mL/min/1.73 m2) 0.6 -3.2 -4.1
Week 26 Change Creatinine (mg/dL) 0.02 0.08 0.10
eGFR (mL/min/1.73 m2) 0.0 -2.7 -2.6
Renal-related adverse reactions (e.g., acute kidney injury, renal impairment, acute prerenal failure) may occur in patients treated with ertugliflozin, particularly in patients with moderate renal impairment where the incidence of renal-related adverse reactions was 0.6%, 2