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.  

 

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

(N = 209) Ertugliflozin

5 mg

(N = 207) Ertugliflozin

15 mg

(N = 205) 

Overall [N (%)]  9 (4.3) 15 (7.2) 16 (7.8) 

Severe [N (%)]  1 (0.5) 1 (0.5) 0 (0.0) 

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) 

Genital Mycotic Infections 

 

In the pool of three placebo-controlled clinical trials, the incidence of female genital mycotic infections (e.g., genital candidiasis, genital infection fungal, vaginal infection, vulvitis, vulvovaginal candidiasis, vulvovaginal mycotic infection, vulvovaginitis) occurred in 3%, 9.1%, and 12.2%, of females treated with placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg, respectively (see Table 1). In females, discontinuation due to genital mycotic infections occurred in 0% and 0.6% of patients treated with placebo and ertugliflozin, respectively.

 

In the same pool, male genital mycotic infections (e.g., balanitis candida, balanoposthitis, genital infection, genital infection fungal) occurred in 0.4%, 3.7%, and 4.2% of males treated with placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg, respectively. Male genital mycotic infections occurred more commonly in uncircumcised males. In males, discontinuations due to genital mycotic infections occurred in 0% and 0.2% of patients treated with placebo and ertugliflozin, respectively. Phimosis was reported in 8 of 1,729 (0.5%) male ertugliflozin-treated patients, of which four required circumcision. 

 

Metformin 

 

The most common (5% or greater incidence) established adverse reactions due to initiation of metformin therapy are diarrhea, nausea, vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache.

 

Long-term treatment with metformin has been associated with a decrease in vitamin B12 absorption, which may very rarely result in clinically significant vitamin B12 deficiency (e.g., megaloblastic anemia). 

Laboratory Tests 

Ertugliflozin