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=158 Ertugliflozin 15 mg

N=155 

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%, 2.5%, and 1.3% in patients treated with placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg, respectively.

Lower Limb Amputation 

Across seven Phase 3 clinical trials in which ertugliflozin was studied as monotherapy and in combination with other antihyperglycemic agents, non-traumatic lower limb amputations occurred in 1 of 1,450 (0.1%) in the non-ertugliflozin group, 3 of 1,716 (0.2%) in the ertugliflozin 5 mg group, and 8 of 1,693 (0.5%) in the ertugliflozin 15 mg group.

Hypoglycemia 

The incidence of hypoglycemia by study is shown in Table 3.

Table 3: Incidence of Overall* and Severe† Hypoglycemia in Placebo-Controlled Clinical Studies in Patients with Type 2 Diabetes Mellitus 

* Overall hypoglycemic events: plasma or capillary glucose of less than or equal to 70 mg/dL. † Severe hypoglycemic events: required assistance, lost consciousness, or experienced a seizure regardless of blood glucose.  

Factorial Study with Sitagliptin as Add-on Combination Therapy with Metformin (26 weeks)  Ertugliflozin 5 mg + Sitagliptin

(N = 243) Ertugliflozin 15 mg + Sitagliptin

(N = 244) 

Overall [N (%)]  13 (5.3) 22 (9.0) 

Severe [N (%)]  0 (0.0) 1 (0.4) 

Add-on Combination Therapy with Metformin and Sitagliptin (26 weeks) Placebo

(N = 153) Ertugliflozin 5 mg

(N = 156) Ertugliflozin 15 mg

(N = 153) 

Overall [N (%)] 5 (3.3) 7 (4.5) 3 (2.0) 

Severe [N (%)] 1 (0.7) 1 (0.6) 0 (0.0) 

Initial Combination Therapy with Sitagliptin (26 weeks) Placebo

(N = 97) Ertugliflozin 5 mg + Sitagliptin

(N = 98) Ertugliflozin 15 mg + Sitagliptin

(N = 96) 

Overall [N (%)] 1 (1.0) 6 (6.1) 3 (3.1) 

Severe [N (%)] 0 (0.0) 0 (0.0) 2 (2.1) 

Genital Mycotic Infections