The mean baseline systolic blood pressure was 129.3 mmHg, 130.5 mmHg, and 130.2 mmHg in the placebo, STEGLATRO 5 mg, and STEGLATRO 15 mg groups, respectively. The mean changes from baseline to Week 26 were -1.8 mmHg, -5.1 mmHg, and -5.7 mmHg in the placebo, STEGLATRO 5 mg, and STEGLATRO 15 mg groups, respectively. The difference from placebo (95% CI) for STEGLATRO 5 mg was -3.3 mmHg (-5.6, -1.1) and for STEGLATRO 15 g was -3.8 mmHg (-6.1, -1.5).

 

Active Controlled Study versus Glimepiride as Add-on Combination Therapy with Metformin  

 

A total of 1,326 patients with type 2 diabetes mellitus inadequately controlled (HbA1c between 7% and 9%) on metformin monotherapy participated in a randomized, double-blind, multi-center, 52-week, active comparator controlled study (NCT01999218) to eva luate the efficacy and safety of STEGLATRO in combination with metformin. These patients, who were receiving metformin monotherapy (≥1,500 mg/day for ≥8 weeks), entered a 2-week, single-blind, placebo run-in period and were randomized to glimepiride, STEGLATRO 5 mg, or STEGLATRO 15 mg administered once daily in addition to continuation of background metformin therapy. Glimepiride was initiated at 1 mg/day and titrated up to a maximum dose of 6 or 8 mg/day (depending on maximum approved dose in each country) or a maximum tolerated dose or down-titrated to avoid or manage hypoglycemia. The mean daily dose of glimepiride was 3.0 mg.

 

STEGLATRO 15 mg was non-inferior to glimepiride after 52 weeks of treatment. (See Table 6.)

Table 6: Results at Week 52 from an Active-Controlled Study Comparing STEGLATRO to Glimepiride as Add-on Therapy in Patients with Type 2 Diabetes Mellitus Inadequately Controlled on Metformin* 

 

Glimepiride

 

STEGLATRO 5 mg

 

STEGLATRO 15 mg

 

* N includes all randomized and treated patients with a baseline measurement of the outcome variable. At Week 52, the primary HbA1c endpoint was missing for 15%, 20%, and 16% of patients and during the trial, rescue medication was initiated by 3%, 6%, and 4% of patients randomized to glimepiride, STEGLATRO 5 mg, and STEGLATRO 15 mg, respectively. Missing Week 52 measurements were imputed using multiple imputation with a mean equal to the baseline value of the patient. Results include measurements collected after initiation of rescue medication. For those patients who did not receive rescue medication and had values measured at 52 weeks, the mean changes from baseline for HbA1c were -0.8%, -0.6%, and -0.7% for glimepiride, STEGLATRO 5 mg, and STEGLATRO 15 mg, respectively. † Intent-to-treat analysis using ANCOVA adjusted for baseline value, prior antihyperglycemic medication and baseline eGFR. ‡ Non-inferiority is declared when the upper bound of the two-sided 95% confidence interval (CI) for the mean difference is less than 0.3%.  

 

HbA1c (%) N = 437 N = 447 N = 440 

  Baseline (mean) 7.8 7.8 7.8 

  Change from baseline (LS mean†) -0.6 -0.5 -0.5 

  Difference from glimepiride (LS mean†, 95% CI)  0.2‡ (0.0, 0.3) 0.1‡ (-0.0, 0.2)