Trial Outcomes & Findings for Safety and Efficacy of Bexagliflozin Compared to Placebo as Add-on Therapy to Metformin in Type 2 Diabetes Subjects (NCT NCT03259789)

NCT ID: NCT03259789

Last Updated: 2021-07-07

Results Overview

HbA1c was obtained at baseline and at Week 24. The model-adjusted change from baseline was calculated using mixed-effects repeated measures analysis.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 351 participants
• Primary outcome timeframe: Baseline to week 24
• Results posted on: 2021-07-07

Participant Flow

Participant milestones

Measure	Double-blind Group: Bexagliflozin 20 mg Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	Double-blind Group: Placebo Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	High Glycemic Group Each subject will receive Bexagliflozin tablet, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
Overall Study STARTED	158	159	34
Overall Study COMPLETED	141	142	28
Overall Study NOT COMPLETED	17	17	6

Reasons for withdrawal

Measure	Double-blind Group: Bexagliflozin 20 mg Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	Double-blind Group: Placebo Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	High Glycemic Group Each subject will receive Bexagliflozin tablet, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
Overall Study Adverse Event	3	2	1
Overall Study Withdrawal by Subject	9	5	1
Overall Study Lost to Follow-up	5	9	4
Overall Study Physician Decision	0	1	0

Baseline Characteristics

For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.

Baseline characteristics by cohort

Measure	Double-blind Group: Bexagliflozin 20 mg n=158 Participants Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	Double-blind Group: Placebo n=159 Participants Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	High Glycemic Group n=34 Participants Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	Total n=351 Participants Total of all reporting groups
Age, Continuous Double-blind Group	56.0 years STANDARD_DEVIATION 10.05 • n=158 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.	55.6 years STANDARD_DEVIATION 11.18 • n=159 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.	—	55.8 years STANDARD_DEVIATION 10.62 • n=317 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.
Age, Continuous High Glycemic Group	—	—	52.1 years STANDARD_DEVIATION 8.59 • n=34 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.	52.1 years STANDARD_DEVIATION 8.59 • n=34 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.
Sex: Female, Male Female	58 Participants n=158 Participants	65 Participants n=159 Participants	15 Participants n=34 Participants	138 Participants n=351 Participants
Sex: Female, Male Male	100 Participants n=158 Participants	94 Participants n=159 Participants	19 Participants n=34 Participants	213 Participants n=351 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	35 Participants n=158 Participants	32 Participants n=159 Participants	9 Participants n=34 Participants	76 Participants n=351 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	123 Participants n=158 Participants	127 Participants n=159 Participants	25 Participants n=34 Participants	275 Participants n=351 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=158 Participants	0 Participants n=159 Participants	0 Participants n=34 Participants	0 Participants n=351 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=158 Participants	1 Participants n=159 Participants	1 Participants n=34 Participants	3 Participants n=351 Participants
Race (NIH/OMB) Asian	78 Participants n=158 Participants	79 Participants n=159 Participants	9 Participants n=34 Participants	166 Participants n=351 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=158 Participants	0 Participants n=159 Participants	1 Participants n=34 Participants	2 Participants n=351 Participants
Race (NIH/OMB) Black or African American	26 Participants n=158 Participants	29 Participants n=159 Participants	12 Participants n=34 Participants	67 Participants n=351 Participants
Race (NIH/OMB) White	51 Participants n=158 Participants	48 Participants n=159 Participants	11 Participants n=34 Participants	110 Participants n=351 Participants
Race (NIH/OMB) More than one race	1 Participants n=158 Participants	2 Participants n=159 Participants	0 Participants n=34 Participants	3 Participants n=351 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=158 Participants	0 Participants n=159 Participants	0 Participants n=34 Participants	0 Participants n=351 Participants
Region of Enrollment United States	83 participants n=158 Participants	83 participants n=159 Participants	27 participants n=34 Participants	193 participants n=351 Participants
Region of Enrollment Japan	75 participants n=158 Participants	76 participants n=159 Participants	7 participants n=34 Participants	158 participants n=351 Participants
Height Double-blind Group	168.4 cm STANDARD_DEVIATION 9.71 • n=158 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.	167.3 cm STANDARD_DEVIATION 9.55 • n=159 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.	—	167.8 cm STANDARD_DEVIATION 9.63 • n=317 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.
Height High Glycemic Group	—	—	169.4 cm STANDARD_DEVIATION 9.34 • n=34 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.	169.4 cm STANDARD_DEVIATION 9.34 • n=34 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.
Body Weight Double-blind Group	84.58 kg STANDARD_DEVIATION 21.989 • n=158 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.	84.44 kg STANDARD_DEVIATION 20.928 • n=159 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.	—	84.51 kg STANDARD_DEVIATION 21.43 • n=317 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.
Body Weight High Glycemic Group	—	—	87.28 kg STANDARD_DEVIATION 17.759 • n=34 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.	87.28 kg STANDARD_DEVIATION 17.759 • n=34 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.
BMI Double-blind Group	29.67 kg/m^2 STANDARD_DEVIATION 6.45 • n=158 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.	29.99 kg/m^2 STANDARD_DEVIATION 6.342 • n=159 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.	—	29.83 kg/m^2 STANDARD_DEVIATION 6.388 • n=317 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.
BMI High Glycemic Group	—	—	30.37 kg/m^2 STANDARD_DEVIATION 5.558 • n=34 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.	30.37 kg/m^2 STANDARD_DEVIATION 5.558 • n=34 Participants • For the Double-blind group, the High Glycemic group is excluded. Therefore, the number of participants analyzed is 317. Conversely, for the High Glycemic group, the Double-blind group is excluded. Therefore, the number of participants analyzed is 34.

PRIMARY outcome

Timeframe: Baseline to week 24

Population: The intention-to-treat (ITT) population was used for the primary analysis. Subjects with a value at baseline and at week 24 were analyzed.

HbA1c was obtained at baseline and at Week 24. The model-adjusted change from baseline was calculated using mixed-effects repeated measures analysis.

Outcome measures

Measure	Double-blind Group: Bexagliflozin 20 mg n=142 Participants Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	Double-blind Group: Placebo n=145 Participants Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	High Glycemic Group Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
Change From Baseline in HbA1c at Week 24 for Double-blind Group	-1.09 percentage of HbA1c Standard Error 0.076	-0.56 percentage of HbA1c Standard Error 0.075	—

PRIMARY outcome

Timeframe: Baseline to week 24

Population: The intention-to-treat (ITT) population was used for the primary analysis. Subjects with a value at baseline and at week 24 were analyzed.

The change in HbA1c from baseline at Week 24 in High Glycemic Group was calculated by subtracting the mean HbA1c at baseline from the mean HbA1c at Week 24

Outcome measures

Measure	Double-blind Group: Bexagliflozin 20 mg n=29 Participants Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	Double-blind Group: Placebo Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	High Glycemic Group Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
Change From Baseline in HbA1c at Week 24 for High Glycemic Group	-2.82 percentage of HbA1c Standard Deviation 1.084	—	—

SECONDARY outcome

Timeframe: Baseline, up to 24 weeks

Population: ITT population was used for the analysis. Subjects with a value at baseline and at week 24 were analyzed.

FPG was obtained at baseline and at Week 24. The model-adjusted change from baseline was calculated using mixed-effects repeated measures analysis.

Outcome measures

Measure	Double-blind Group: Bexagliflozin 20 mg n=142 Participants Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	Double-blind Group: Placebo n=145 Participants Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	High Glycemic Group Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 for Double-blind Group	-2.51 mmol/L Standard Error 0.174	-1.16 mmol/L Standard Error 0.173	—

SECONDARY outcome

Timeframe: Baseline, up to 24 weeks

Population: ITT population was used for the analysis. Subjects with a value at baseline and at week 24 were analyzed.

The change in FPG from baseline at Week 24 for High Glycemic Group was calculated by subtracting the mean FPG at baseline from the mean FPG at Week 24

Outcome measures

Measure	Double-blind Group: Bexagliflozin 20 mg n=29 Participants Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	Double-blind Group: Placebo Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	High Glycemic Group Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 24 for High Glycemic Group	-4.98 mmol/L Standard Deviation 3.437	—	—

SECONDARY outcome

Timeframe: Baseline to week 24

Population: The ITT population was used for the analysis. Subjects with a value at baseline and at the specific visit were analyzed.

Changes from baseline at Week 24 in SBP for the double-blind group and high glycemic group

Outcome measures

Measure	Double-blind Group: Bexagliflozin 20 mg n=143 Participants Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	Double-blind Group: Placebo n=145 Participants Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	High Glycemic Group n=29 Participants Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
Change From Baseline in Systolic Blood Pressure (SBP) at Week 24	-5.03 mm Hg Standard Error 0.993	2.04 mm Hg Standard Error 0.987	-8.19 mm Hg Standard Error 14.882

SECONDARY outcome

Timeframe: Baseline, up to 24 weeks

Population: The number of subjects in the ITT population with a value at baseline and at the specified visit was included. Model-adjusted proportion (LS proportion) and 95% confidence interval were reported for Double-blind Treatment Group.

The proportion of subjects who achieved HbA1c < 7% at 6, 12, 18 and 24 weeks were calculated based on the number of subjects with a value at each time point for each group. The model-adjusted proportion was calculated based on a logistic analysis using Generalized Estimating Equation (GEE) logistic regression that includes country, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate. An unstructured correlation structure will be used, or autoregressive if the model with the unstructured structure does not converge.

Outcome measures

Measure	Double-blind Group: Bexagliflozin 20 mg n=158 Participants Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	Double-blind Group: Placebo n=159 Participants Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	High Glycemic Group Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
Proportion of Subjects Achieving HbA1c < 7% Over Time for Double-blind Group Week 6	0.14 Proportion of subjects Interval 0.09 to 0.23	0.03 Proportion of subjects Interval 0.01 to 0.07	—
Proportion of Subjects Achieving HbA1c < 7% Over Time for Double-blind Group Week 12	0.26 Proportion of subjects Interval 0.18 to 0.38	0.06 Proportion of subjects Interval 0.03 to 0.12	—
Proportion of Subjects Achieving HbA1c < 7% Over Time for Double-blind Group Week 18	0.26 Proportion of subjects Interval 0.18 to 0.39	0.10 Proportion of subjects Interval 0.06 to 0.18	—
Proportion of Subjects Achieving HbA1c < 7% Over Time for Double-blind Group Week 24	0.38 Proportion of subjects Interval 0.26 to 0.55	0.10 Proportion of subjects Interval 0.06 to 0.17	—

SECONDARY outcome

Timeframe: Baseline, up to 24 weeks

Population: The number of subjects in the ITT population with a value at baseline and at the specified visit was included. Proportion of subjects achieving HbA1c \< 7% was reported for High Glycemic Group without a 95% confidence interval.

The proportion of subjects who achieved HbA1c < 7% at 6, 12, 18 and 24 weeks were calculated based on the number of subjects with a value at each time point for each group.

Outcome measures

Measure	Double-blind Group: Bexagliflozin 20 mg n=34 Participants Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	Double-blind Group: Placebo Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	High Glycemic Group Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
Proportion of Subjects Achieving HbA1c < 7% Over Time for High Glycemic Group Week 6	0 Proportion of subjects	—	—
Proportion of Subjects Achieving HbA1c < 7% Over Time for High Glycemic Group Week 12	0.065 Proportion of subjects	—	—
Proportion of Subjects Achieving HbA1c < 7% Over Time for High Glycemic Group Week 18	0.097 Proportion of subjects	—	—
Proportion of Subjects Achieving HbA1c < 7% Over Time for High Glycemic Group Week 24	0.138 Proportion of subjects	—	—

SECONDARY outcome

Timeframe: Baseline to week 24

Population: Subjects with a BMI \>= 25 kg/m2 at baseline in the ITT population were included. The number of subjects with a value at baseline and at week 24 was analyzed. Model-adjusted mean change (LS Mean) and standard error (SE) were reported.

Changes in body mass from baseline to week 24 was calculated based on LS means for both bexagliflozin and placebo groups.

Outcome measures

Measure	Double-blind Group: Bexagliflozin 20 mg n=119 Participants Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	Double-blind Group: Placebo n=124 Participants Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	High Glycemic Group Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
Change in Body Mass From Baseline to Week 24 in Subjects With a BMI ≥ 25 kg/m2 for Double-blind Group	-3.60 kg Standard Error 0.348	-1.09 kg Standard Error 0.336	—

SECONDARY outcome

Timeframe: Baseline to week 24

Population: Subjects with a BMI \>= 25 kg/m2 at baseline in the ITT population were included. The number of subjects with a value at baseline and at week 24 was analyzed.

The change in body mass from baseline at week 24 for High Glycemic group was calculated by subtracting the mean body mass at baseline from the mean body mass at week 24

Outcome measures

Measure	Double-blind Group: Bexagliflozin 20 mg n=28 Participants Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	Double-blind Group: Placebo Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	High Glycemic Group Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
Change in Body Mass From Baseline to Week 24 in Subjects With a BMI ≥ 25 kg/m2 for High Glycemic Group	-1.40 kg Standard Deviation 3.759	—	—

SECONDARY outcome

Timeframe: Baseline, up to 24 weeks

Population: The Number Analyzed only includes the number of subjects with a value at baseline and at the specific visit. Model-adjusted mean change (LS Mean) and standard error (SE) were reported for Double-blind Treatment Group.

The change from baseline in HbA1c at 6, 12, 18 and 24 weeks was calculated based on the number of subjects with a value at each time point for each group. The model-adjusted change from baseline was calculated based on a mixed-effects repeated measures analysis that includes country, treatment, visit, treatment-by-visit interaction and the baseline HbA1c value as a fixed effect covariate.

Outcome measures

Measure	Double-blind Group: Bexagliflozin 20 mg n=158 Participants Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	Double-blind Group: Placebo n=159 Participants Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	High Glycemic Group Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
Change From Baseline in HbA1c Over Time in Double-blind Treatment Group Week 6	-0.72 percentage of HbA1c Standard Error 0.065	-0.16 percentage of HbA1c Standard Error 0.065	—
Change From Baseline in HbA1c Over Time in Double-blind Treatment Group Week 12	-0.97 percentage of HbA1c Standard Error 0.073	-0.31 percentage of HbA1c Standard Error 0.073	—
Change From Baseline in HbA1c Over Time in Double-blind Treatment Group Week 18	-1.00 percentage of HbA1c Standard Error 0.072	-0.51 percentage of HbA1c Standard Error 0.072	—
Change From Baseline in HbA1c Over Time in Double-blind Treatment Group Week 24	-1.09 percentage of HbA1c Standard Error 0.076	-0.56 percentage of HbA1c Standard Error 0.075	—

SECONDARY outcome

Timeframe: Baseline, up to 24 weeks

Population: The Number Analyzed only includes the number of subjects with a value at baseline and at the specific visit.

The change from baseline in HbA1c at 6, 12, 18 and 24 weeks was calculated based on the number of subjects with a value at each time point in High Glycemic Group.

Outcome measures

Measure	Double-blind Group: Bexagliflozin 20 mg n=34 Participants Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	Double-blind Group: Placebo Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	High Glycemic Group Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
Change in HbA1c Over Time Among Subjects Who Have Baseline HbA1c of > 10.5% and ≤ 12.0% Week 6	-1.72 percentage of HbA1c Standard Deviation 1.027	—	—
Change in HbA1c Over Time Among Subjects Who Have Baseline HbA1c of > 10.5% and ≤ 12.0% Week 12	-2.45 percentage of HbA1c Standard Deviation 1.136	—	—
Change in HbA1c Over Time Among Subjects Who Have Baseline HbA1c of > 10.5% and ≤ 12.0% Week 18	-2.62 percentage of HbA1c Standard Deviation 1.055	—	—
Change in HbA1c Over Time Among Subjects Who Have Baseline HbA1c of > 10.5% and ≤ 12.0% Week 24	-2.82 percentage of HbA1c Standard Deviation 1.084	—	—

Adverse Events

Double-blind Group: Bexagliflozin 20 mg

Serious events: 3 serious events

Other events: 16 other events

Deaths: 0 deaths

Double-blind Group: Placebo

Serious events: 4 serious events

Other events: 28 other events

Deaths: 0 deaths

High Glycemic Group

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	Double-blind Group: Bexagliflozin 20 mg n=158 participants at risk Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	Double-blind Group: Placebo n=159 participants at risk Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	High Glycemic Group n=34 participants at risk Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
Cardiac disorders Acute coronary syndrome	0.63% 1/158 • Number of events 1 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	0.00% 0/159 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	0.00% 0/34 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).
Cardiac disorders Atrial fibrillation	0.00% 0/158 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	0.63% 1/159 • Number of events 1 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	0.00% 0/34 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).
Gastrointestinal disorders Constipation	0.00% 0/158 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	0.63% 1/159 • Number of events 1 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	0.00% 0/34 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).
Metabolism and nutrition disorders Diabetic ketoacidosis	0.63% 1/158 • Number of events 1 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	0.00% 0/159 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	0.00% 0/34 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).
Respiratory, thoracic and mediastinal disorders Asthma	0.00% 0/158 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	0.63% 1/159 • Number of events 1 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	0.00% 0/34 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.00% 0/158 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	0.63% 1/159 • Number of events 1 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	0.00% 0/34 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).
Vascular disorders Hypertension	0.00% 0/158 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	0.63% 1/159 • Number of events 1 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	0.00% 0/34 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).
Cardiac disorders Acute cardiac failure	0.63% 1/158 • Number of events 1 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	0.00% 0/159 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	0.00% 0/34 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).

Other adverse events

Measure	Double-blind Group: Bexagliflozin 20 mg n=158 participants at risk Each subject will receive bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	Double-blind Group: Placebo n=159 participants at risk Each subject will receive placebo (inactive tablet) once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.	High Glycemic Group n=34 participants at risk Each subject will receive Bexagliflozin, 20 mg, once daily and open-labeled metformin background medication during the entire study at a stable dose and frequency.
Metabolism and nutrition disorders Diabetes mellitus inadequate control	1.9% 3/158 • Number of events 3 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	6.3% 10/159 • Number of events 10 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	2.9% 1/34 • Number of events 1 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).
Investigations Glomerular filtration rate decreased	0.00% 0/158 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	0.00% 0/159 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	5.9% 2/34 • Number of events 2 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).
Infections and infestations Nasopharyngitis	5.7% 9/158 • Number of events 9 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	8.2% 13/159 • Number of events 13 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	2.9% 1/34 • Number of events 1 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).
Metabolism and nutrition disorders Polydipsia	3.2% 5/158 • Number of events 6 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	2.5% 4/159 • Number of events 4 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	8.8% 3/34 • Number of events 3 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).
Renal and urinary disorders Polyuria	3.2% 5/158 • Number of events 7 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	3.8% 6/159 • Number of events 6 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).	11.8% 4/34 • Number of events 4 • Adverse events were collected from Week -1 (run in period: Visit 2) to Week 26 (Follow up: Visit 8).

Additional Information

Albert Collinson

Theracos Sub, LLC

Phone: (508) 630-2129

Email: acollinson@theracos.com

Results disclosure agreements

• Principal investigator is a sponsor employee The investigator does not have the right to publish trial results.
• Publication restrictions are in place

Restriction type: OTHER