The mean baseline systolic blood pressure was 128.4 mmHg, 129.7 mmHg, 128.9 mmHg, 130.2 mmHg, and 129.1 mmHg in the sitagliptin 100 mg, ertugliflozin 5 mg, ertugliflozin 15 mg , ertugliflozin 5 mg + sitagliptin 100 mg, and ertugliflozin 15 mg + sitagliptin 100 mg groups, respectively. The mean changes from baseline to Week 26 were -0.5 mmHg, -4.0 mmHg, -3.6 mmHg, -2.8 mmHg, and -3.4 mmHg in the sitagliptin 100 mg, ertugliflozin 5 mg, ertugliflozin 15 mg, ertugliflozin 5 mg + sitagliptin 100 mg, and ertugliflozin 15 mg + sitagliptin 100 mg groups, respectively. The difference from sitagliptin 100 mg (95% CI) for ertugliflozin 5 mg + sitagliptin 100 mg was -2.3 mmHg (-4.3, -0.4) and for ertugliflozin 15 mg + sitagliptin 100 mg was -2.9 mmHg (-4.8, -1.0).

Figure 3: HbA1c (%) Change over Time in a Factorial Study with Ertugliflozin and Sitagliptin as Add-on Combination Therapy with Metformin Compared to Individual Components Alone*

* Data to the left of the vertical line are observed means (non-model-based) excluding values occurring post glycemic rescue. Data to the right of the vertical line represent the final Week 26 data, including all values regardless of use of glycemic rescue medication and use of study drug, with missing Week 26 values imputed using multiple imputation (26-MI) with a mean equal to the baseline value of the patient (see Table 6).  

Figure 3

14.3 Ertugliflozin as Add-on Combination Therapy with Metformin and Sitagliptin

A total of 463 patients with type 2 diabetes mellitus inadequately controlled (HbA1c between 7% and 10.5%) on metformin (≥1,500 mg/day for ≥8 weeks) and sitagliptin 100 mg once daily participated in a randomized, double-blind, multi-center, 26-week, placebo-controlled study (NCT02036515) to eva luate the efficacy and safety of ertugliflozin. Patients entered a 2-week, single-blind, placebo run-in period and were randomized to placebo, ertugliflozin 5 mg, or ertugliflozin 15 mg.

At Week 26, treatment with ertugliflozin at 5 mg or 15 mg daily provided statistically significant reductions in in HbA1c. Ertugliflozin also resulted in a higher proportion of patients achieving an HbA1c <7% compared to placebo (see Table 7).

Table 7: Results at Week 26 from an Add-on Study of Ertugliflozin in Combination with Metformin and Sitagliptin in Patients with Type 2 Diabetes Mellitus* 

Placebo

Ertugliflozin 5 mg

Ertugliflozin 15 mg

* N includes all randomized and treated patients with a baseline measurement of the outcome variable. At Week 26, the primary HbA1c endpoint was missing for 10%, 11%, and 7% of patients and during the trial, rescue medication was initiated by 16%, 1%, and 2% of patients randomized to placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg, respectively. Missing Week 26 measurements were imputed using multiple imputation with a mean equal to the baseline value of the patient. Results included measurements collected after initiation of rescue medication. For those patients who did not receive rescue medication and had values measured at 26 weeks, the mean changes from baseline for HbA1c were -0.2%, -0.8%, and -0.9% for placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg, respectively. † Intent-to-treat analysis using ANCOVA adjusted for baseline value, prior antihyperglycemic medication and baseline eGFR. ‡ p<0.001 compared to placebo.  

HbA1c (%) N = 152 N = 155 N = 152