• Urosepsis and Pyelonephritis [see Warnings and Precautions (5.6)]

• Hypoglycemia with Concomitant Use of Insulin or Insulin Secretagogues [see Warnings and Precautions (5.7)]

• Hypersensitivity Reactions [see Warnings and Precautions (5.8)]

• Genital Mycotic Infections [see Warnings and Precautions (5.9)]

• Increases in Low-Density Lipoprotein Cholesterol (LDL-C) [see Warnings and Precautions (5.10)]

• Bladder Cancer [see Warnings and Precautions (5.11)]

• Severe and Disabling Arthralgia [see Warnings and Precautions (5.12)]

• Bullous Pemphigoid [see Warnings and Precautions (5.13)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of combined use of 10 mg dapagliflozin and 5 mg saxagliptin has been eva luated in 492 adult subjects with type 2 diabetes in a pooled safety analysis of three phase 3 active/placebo-controlled clinical trials with a median exposure of 51 weeks. The mean age of these subjects was 54 years, 0.8% were 75 years or older and 53.7% were female. The population was 80.9% White, 8.3% Black or African American, 3.7% Asian, and 6.6% Other race. At baseline the population had diabetes for an average of 7.5 years and a mean HbA1c of 8.4%. The mean eGFR at baseline was 94.4 mL/min/1.73 m2.

The common adverse reactions were based on the pooled analyses of these studies as shown in Table 1.

Table 1. Adverse Reactions Reported in ≥2% Subjects Treated with 10 mg Dapagliflozin and 5 mg Saxagliptin

* Adverse reactions that are medically related were grouped to a single preferred term.

Additionally, adverse reactions reported in <5% and ≥2% from the dapagliflozin development program and ≥1% more frequently compared to placebo included increased urination, and discomfort with urination.

Hypoglycemia

Hypoglycemia was reported in 8 subjects (1.6%) treated with QTERN. No episodes of major hypoglycemia (defined as a symptomatic episode requiring external assistance) were reported.

Genital Mycotic Infections

Genital mycotic infections were reported in 15 subjects (3%) treated with QTERN. Reported adverse reactions by frequency included vulvovaginal mycotic infection, balanoposthitis, genital fungal infection, vaginal infection, and vulvovaginitis. The majority of subjects (84.2%) who experienced genital infection adverse reactions were females.

Urinary Tract Infections

Urinary tract infections were reported in 28 subjects (5.7%) treated with QTERN. Reported adverse reactions by frequency included urinary tract infection, Escherichia urinary tract infection, prostatitis, and pyelonephritis. The majority of subjects (80.6%) who experienced urinary tract infection adverse reactions were females.

Volume Depletion

Events related to volume depletion (hypotension, dehydration, and hypovolemia) were reported in 2 subjects (0.4%) treated with QTERN.

Renal Impairment
Adverse reactions related to decreased renal function were reported in 10 subjects (2.0%) treated with QTERN. The reported adverse reactions included decreased glomer