ular filtration rate, renal impairment, increased blood creatinine, acute renal failure, and decreased urine output. None of the adverse reactions was reported as serious and all but one were mild to moderate in intensity. Three subjects discontinued due to decreased eGFR. Subjects with AEs of renal impairment had lower mean eGFR values at baseline of 64.4 ml/min/1.73 m2 compared to 94.4 ml/min/1.73 m2 in overall population treated with QTERN.
Dapagliflozin
Use of dapagliflozin was associated with increases in serum creatinine and decreases in eGFR (see Table 2). In patients with normal or mildly impaired renal function at baseline, serum creatinine and eGFR returned to baseline values at Week 24. Sustained decreases in eGFR were seen in patients with moderate renal impairment (eGFR 30 to less than 60 mL/min/1.73 m2). Elderly patients and patients with impaired renal function were more susceptible to these adverse reactions.
Table 2. Changes in Serum Creatinine and eGFR Associated with Dapagliflozin
Laboratory Findings
Decrease in Lymphocyte Counts
Saxagliptin
A dose-related mean decrease in absolute lymphocyte count has been observed with saxagliptin. In a pool of 5 placebo-controlled studies, a mean decrease in absolute lymphocyte count of approximately 100 cells/microL relative to placebo. There was a dose-related mean decrease in absolute lymphocyte count observed with saxagliptin. The proportion of patients who were reported to have a lymphocyte count ≤750 cells/microL was 0.5%, 1.5%, and 0.4% in the saxagliptin 2.5 mg, 5 mg, and placebo groups, respectively. The decreases in lymphocyte count were not associated with clinically relevant adverse reactions.
The clinical significance of this decrease in lymphocyte count relative to placebo is not known. When clinically indicated, such as in settings of unusual or prolonged infection, lymphocyte count should be measured. The effect of saxagliptin on lymphocyte counts in patients with lymphocyte abnormalities (e.g., human immunodeficiency virus) is unknown.
Increase in Hematocrit
Dapagliflozin
In a pool of 13 placebo-controlled studies with dapagliflozin, increases from baseline in mean hematocrit values were observed in dapagliflozin treated patients starting at Week 1 and continuing up to Week 16, when the maximum mean difference from baseline was observed. At Week 24, the mean changes from baseline in hematocrit were −0.33% in the placebo group and 2.30% in the dapagliflozin 10 mg group. By Week 24, hematocrit values >55% were reported in 0.4% of placebo-treated patients and 1.3% of dapagliflozin 10 mg-treated patients.
Increase in Serum Inorganic Phosphorus
Dapagliflozin
In a pool of 13 placebo-controlled studies with dapagliflozin, increases from baseline in mean serum phosphorus levels were reported at Week 24 in dapagliflozin treated patients compared with placebo-treated patients (mean increase of 0.13 versus −0.04 mg/dL, respectively). Higher proportions of patients with marked laboratory abnormalities of hyperphosphatemia (≥5.6 mg/dL for age 17-65 years or ≥5.1 mg/dL for age ≥66 years) were reported on dapagliflozin at Week 24 (0.9% versus 1.7% for placebo and dapagliflozin 10 mg, respectively).
Increase in Low-Density Lipoprotein Cholesterol
Patients treated with QTERN demonstrated a mean percent increase from baseline LDL-cholesterol (ranging from 2.1 to 6.9%).
