Safety and Efficacy of Bexagliflozin Compared to Glimepiride as Add-on Therapy to Metformin in Type 2 Diabetes Subjects

• Sponsor: Theracos (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02769481
• Collaborator: (none)
• Enrollment: 426
• Locations: 45
• Arms: 2
• Actual Duration (Months): 33.9
• Patients Per Site: 9.5
• Patients Per Site Per Month: 0.3

Study Details

Study Description

Brief Summary

The purpose of this study is to investigate the effect of bexagliflozin compared to glimepiride as an add-on therapy to metformin in lowering hemoglobin A1c (HbA1c) levels in subjects with type 2 diabetes mellitus (T2DM).

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Bexagliflozin; Drug: Placebo for Bexagliflozin; Drug: Glimepiride; Drug: Placebo for Glimepiride	Phase 3

Detailed Description

Approximately 420 subjects with inadequately controlled T2DM on metformin will be recruited from North America and Europe. Subjects will be randomly assigned to receive bexagliflozin tablets, 20 mg, or glimepiride capsules, 2, 4 or 6 mg, in a ratio of 1:1 once daily for 96 weeks. Subjects will continue to take metformin for the duration of the study.

Study Design

• Study Type: Interventional
• Actual Enrollment: 426 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Randomized, Double-blind, Active-controlled Study to Evaluate the Effects of Bexagliflozin Versus Glimepiride in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control by Metformin
• Actual Study Start Date: Aug 15, 2016
• Actual Primary Completion Date: Jun 14, 2019
• Actual Study Completion Date: Jun 14, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Bexagliflozin Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for glimepiride daily for the duration of the study.	Drug: Bexagliflozin; 20 mg, tablet; Other Names: EGT0001442 ; Drug: Placebo for Glimepiride; inactive capsules to match active comparator glimepiride
Active Comparator: Glimepiride Subjects will receive a glimepiride capsule, 2, 4 or 6 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study.	Drug: Placebo for Bexagliflozin; inactive tablet to match active comparator bexagliflozin; Drug: Glimepiride; 2, 4 or 6 mg, capsule

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in HbA1c at Week 60 [Baseline and Week 60]

   The primary objective is to demonstrate that bexagliflozin is non-inferior to glimepiride by evaluating the treatment effect on HbA1c reduction at week 60 in subjects whose T2DM is inadequately controlled by metformin. The least square mean (LSM) change from baseline to Week 60 was analyzed using a mixed model repeated measures (MMRM) analysis of covariance model (ANCOVA).

Secondary Outcome Measures

1. Change From Baseline in Body Weight at Week 60 for Subjects With Baseline BMI ≥ 25 kg/m2 [Baseline and 60 weeks]

   Least squares (LS) mean treatment difference between the bexagliflozin group and placebo group in the change of body weight in subjects with baseline BMI ≥ 25 kg/m2 at week 60 is analyzed using ANCOVA.

2. Change From Baseline in Systolic Blood Pressure (SBP) at Week 60 for Subjects With Baseline SBP ≥ 140 mmHg [Baseline and 60 weeks]

   Least squares (LS) mean treatment difference between the bexagliflozin group and placebo group in the change of SBP in subjects with baseline SBP ≥ 140 mmHg at week 60 is analyzed using ANCOVA.

3. Difference in Proportion of Subjects With ≥ 1 Severe or Documented Symptomatic Hypoglycemia Events Over 96 Weeks [During the 96 week treatment period]

   The difference in proportion of subjects with ≥ 1 severe or documented symptomatic hypoglycemia events in the bexagliflozin group compared with glimepiride group over 96 weeks is analyzed using a logistic regression model. The full model included region, baseline HbA1c value, background treatment status (metformin or metformin + OHA), eGFR at baseline ≥ 90 or < 90 mL min 1 per 1.73 m2), treatment as a fixed effect covariate.

4. Superiority of Bexagliflozin Over Glimepiride in HbA1c Reduction at Week 60. [Baseline to Week 60]

   Superiority of bexagliflozin over glimepiride in HbA1c reduction from baseline to week 60 will be declared if the upper bound of 95% CI is less than 0.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Diagnosis of T2DM

• Currently taking metformin or taking metformin and one additional oral medication for diabetes

• Body Mass Index (BMI) ≤ 45 kg/m2

• Stable dose of blood pressure or cholesterol medications (if applicable) for at least 30 days

Exclusion Criteria:

• Hypersensitivity or other contraindication to the safe use of sulfonylurea or glimepiride

• Diagnosis of type 1 diabetes mellitus or maturity-onset/diabetes of the young

• Current use of injected therapy for treatment of diabetes (insulin or GLP-1 receptor agonist therapy) or thiazolidinedione class drugs

• History of genitourinary tract infections

• Evidence of abnormal liver function

• Myocardial infarction, stroke or hospitalization for heart failure within 3 months of screening

• Prior kidney transplant or evidence of kidney problems

• Pregnant or nursing

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Research Site	Birmingham	Alabama	United States	35205
2	Research Site	Huntington Park	California	United States	90255
3	Research Site	Los Angeles	California	United States	90057
4	Research Site	San Carlos	California	United States	94070
5	Research Site	Hialeah	Florida	United States	33012
6	Research Site	Miami Lakes	Florida	United States	33016
7	Research Site	Orlando	Florida	United States	32806
8	Research Site	West Palm Beach	Florida	United States	33401
9	Research Site	Calabash	North Carolina	United States	28467
10	Research Site	Morehead City	North Carolina	United States	28557
11	Research Site	Magnolia	Texas	United States	77355
12	Research Site	Aschaffenburg		Germany	63739
13	Research Site	Essen		Germany	45277
14	Research Site 2	Essen		Germany	45355
15	Research Site 2	Hamburg		Germany	21073
16	Research Site	Hamburg		Germany	22607
17	Research Site	Heidelberg		Germany	69115
18	Research Site	Magdeburg		Germany	39120
19	Research Site	Wangen		Germany	88239
20	Research Site	Bochnia		Poland	32-700
21	Research Site	Bydgoszcz		Poland	85-312
22	Research Site	Kraków		Poland	30-015
23	Research Site 2	Kraków		Poland	31-011
24	Research Site 2	Lublin		Poland	20-064
25	Research Site	Lublin		Poland	20-362
26	Research Site	Olsztyn		Poland	10-117
27	Research Site	Poznań		Poland	61-655
28	Research Site	Puławy		Poland	24-100
29	Research Site	Staszów		Poland	28-200
30	Research Site	Swarzędz		Poland	62-020
31	Research Site	Toruń		Poland	87-100
32	Research Site	Warszawa		Poland	00-660
33	Research Site	Zamość		Poland	22-400
34	Research Site	Łódź		Poland	90-242
35	Research Site	Świdnik		Poland	21-040
36	Research Site	Alicante		Spain
37	Research Site 2	Barcelona		Spain
38	Research Site	Barcelona		Spain
39	Research Site 2	Madrid		Spain
40	Research Site 3	Madrid		Spain
41	Research Site	Madrid		Spain
42	Research Site 2	Malaga		Spain
43	Research Site	Malaga		Spain
44	Research Site 2	Oviedo		Spain
45	Research Site	Valencia		Spain

Sponsors and Collaborators

• Theracos

Investigators

• Study Director: J. Paul Lock, MD, Theracos Sub, LLC

Study Documents (Full-Text)

• Study Protocol - Oct 27, 2016
• Statistical Analysis Plan - Jun 24, 2019

More Information

Publications

None provided.

• Responsible Party: Theracos
• ClinicalTrials.gov Identifier: NCT02769481
• Other Study ID Numbers: THR-1442-C-480
• First Posted: May 11, 2016
• Last Update Posted: May 27, 2021
• Last Verified: May 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Glimepiride; Bexagliflozin

Study Results

Participant Flow

Arm/Group Title	Bexagliflozin	Glimepiride
Arm/Group Description	Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for glimepiride for the duration of the study. Bexagliflozin tablets: 20 mg Glimepiride capsules: Placebo, inactive capsule to match the active comparator	Subjects will receive a glimepiride capsule, 2, 4 or 6 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. Bexagliflozin: Placebo, inactive tablet to match the active comparator Glimepiride capsules: 2, 4 or 6 mg
Period Title: Overall Study
STARTED	213	213
Study Complete at Week 60	193	192
COMPLETED	180	177
NOT COMPLETED	33	36

Baseline Characteristics

Arm/Group Title	Bexagliflozin	Glimepiride	Total
Arm/Group Description	Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for glimepiride for the duration of the study. Bexagliflozin tablets: 20 mg Glimepiride capsules: Placebo, inactive capsule to match the active comparator	Subjects will receive a glimepiride capsule, 2, 4 or 6 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. Bexagliflozin: Placebo, inactive tablet to match the active comparator Glimepiride capsules: 2, 4 or 6 mg	Total of all reporting groups
Overall Participants	213	213	426
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	59.5 (9.06)	59.7 (10.35)	59.6 (9.71)
Sex: Female, Male (Count of Participants)
Female	95 44.6%	83 39%	178 41.8%
Male	118 55.4%	130 61%	248 58.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	46 21.6%	47 22.1%	93 21.8%
Not Hispanic or Latino	167 78.4%	166 77.9%	333 78.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	9 4.2%	4 1.9%	13 3.1%
Native Hawaiian or Other Pacific Islander	1 0.5%	0 0%	1 0.2%
Black or African American	5 2.3%	4 1.9%	9 2.1%
White	198 93%	204 95.8%	402 94.4%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	1 0.5%	1 0.2%
Region of Enrollment (participants) [Number]
United States	65 30.5%	63 29.6%	128 30%
Poland	74 34.7%	79 37.1%	153 35.9%
Germany	28 13.1%	29 13.6%	57 13.4%
Spain	46 21.6%	42 19.7%	88 20.7%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	166.7 (11.13)	167.1 (9.53)	166.9 (10.35)
Body Weight at Baseline (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	87.95 (19.122)	90.23 (17.616)	89.09 (18.399)
BMI (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	31.45 (4.861)	32.22 (5.155)	31.83 (5.019)
Systolic Blood Pressure at Baseline (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	133.3 (14.88)	134.2 (14.37)	133.8 (14.62)
Systolic Blood Pressure Categories (Count of Participants)
< 140 mm Hg	135 63.4%	138 64.8%	273 64.1%
> 140 mm Hg	78 36.6%	75 35.2%	153 35.9%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in HbA1c at Week 60
Description	The primary objective is to demonstrate that bexagliflozin is non-inferior to glimepiride by evaluating the treatment effect on HbA1c reduction at week 60 in subjects whose T2DM is inadequately controlled by metformin. The least square mean (LSM) change from baseline to Week 60 was analyzed using a mixed model repeated measures (MMRM) analysis of covariance model (ANCOVA).
Time Frame	Baseline and Week 60

Outcome Measure Data

Analysis Population Description

The intention-to-treat population was used for the analysis. Subjects with a value at baseline and at week 60 were analyzed.

Arm/Group Title	Bexagliflozin	Glimepiride
Arm/Group Description	Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for glimepiride for the duration of the study. Bexagliflozin tablets: 20 mg Glimepiride capsules: Placebo, inactive capsule to match the active comparator	Subjects will receive a glimepiride capsule, 2, 4 or 6 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. Bexagliflozin: Placebo, inactive tablet to match the active comparator Glimepiride capsules: 2, 4 or 6 mg
Measure Participants	193	191
Least Squares Mean (Standard Error) [percentage of glycated hemoglin]	-0.70 (0.058)	-0.66 (0.058)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bexagliflozin, Glimepiride
	Comments	The null hypothesis for the primary endpoint was that the change in HbA1c from baseline to week 60 in the bexagliflozin arm would be greater than change in the glimepiride arm by greater than 0.35%.
	Type of Statistical Test	Non-Inferiority
	Comments	A 95% CI was to be calculated to estimate the range of values in which the treatment difference was likely to lie. If the 95% CI fell below the specified non inferiority margin of 0.35%, the non inferiority of bexagliflozin treatment to glimepiride treatment would be demonstrated and the null hypothesis would be rejected.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.05
	Confidence Interval	(2-Sided) 95%; -0.21 to 0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments	A lower value represents a better treatment effect.

2. Secondary Outcome

Title	Change From Baseline in Body Weight at Week 60 for Subjects With Baseline BMI ≥ 25 kg/m2
Description	Least squares (LS) mean treatment difference between the bexagliflozin group and placebo group in the change of body weight in subjects with baseline BMI ≥ 25 kg/m2 at week 60 is analyzed using ANCOVA.
Time Frame	Baseline and 60 weeks

Outcome Measure Data

Analysis Population Description

Number of subjects with a value at baseline and at the specified visit

Arm/Group Title	Bexagliflozin	Glimepiride
Arm/Group Description	Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for glimepiride for the duration of the study. Bexagliflozin tablets: 20 mg Glimepiride capsules: Placebo, inactive capsule to match the active comparator	Subjects will receive a glimepiride capsule, 2, 4 or 6 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. Bexagliflozin: Placebo, inactive tablet to match the active comparator Glimepiride capsules: 2, 4 or 6 mg
Measure Participants	182	182
Least Squares Mean (Standard Error) [kg]	-3.71 (0.285)	0.59 (0.284)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bexagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value is based on one sided statistical tests using a 0.025 level of significance.
	Method	Mixed-effects repeated measures
	Comments	Region, background treatment, baseline HbA1c, baseline eGFR, treatment, visit, treatment-by-visit and baseline weight as a fixed effect covariate.
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-4.31
	Confidence Interval	(2-Sided) 95%; -5.10 to -3.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) at Week 60 for Subjects With Baseline SBP ≥ 140 mmHg
Description	Least squares (LS) mean treatment difference between the bexagliflozin group and placebo group in the change of SBP in subjects with baseline SBP ≥ 140 mmHg at week 60 is analyzed using ANCOVA.
Time Frame	Baseline and 60 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Bexagliflozin	Glimepiride
Arm/Group Description	Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for glimepiride for the duration of the study. Bexagliflozin tablets: 20 mg Glimepiride capsules: Placebo, inactive capsule to match the active comparator	Subjects will receive a glimepiride capsule, 2, 4 or 6 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. Bexagliflozin: Placebo, inactive tablet to match the active comparator Glimepiride capsules: 2, 4 or 6 mg
Measure Participants	74	68
Least Squares Mean (Standard Error) [mm Hg]	-13.48 (1.404)	-6.95 (1.460)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bexagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0008
	Comments	P-value is based on one sided statistical tests using a 0.025 level of significance.
	Method	Mixed-effects repeated measures
	Comments	Region, background treatment, baseline HbA1c, baseline eGFR, treatment, visit, treatment-by-visit and baseline weight as a fixed effect covariate.
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-6.53
	Confidence Interval	(2-Sided) 95%; -10.56 to -2.51
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Difference in Proportion of Subjects With ≥ 1 Severe or Documented Symptomatic Hypoglycemia Events Over 96 Weeks
Description	The difference in proportion of subjects with ≥ 1 severe or documented symptomatic hypoglycemia events in the bexagliflozin group compared with glimepiride group over 96 weeks is analyzed using a logistic regression model. The full model included region, baseline HbA1c value, background treatment status (metformin or metformin + OHA), eGFR at baseline ≥ 90 or < 90 mL min 1 per 1.73 m2), treatment as a fixed effect covariate.
Time Frame	During the 96 week treatment period

Outcome Measure Data

Analysis Population Description

Subjects with post-baseline assessment.

Arm/Group Title	Bexagliflozin	Glimepiride
Arm/Group Description	Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for glimepiride for the duration of the study. Bexagliflozin tablets: 20 mg Glimepiride capsules: Placebo, inactive capsule to match the active comparator	Subjects will receive a glimepiride capsule, 2, 4 or 6 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. Bexagliflozin: Placebo, inactive tablet to match the active comparator Glimepiride capsules: 2, 4 or 6 mg
Measure Participants	213	212
Number (95% Confidence Interval) [Proportion of participants]	0.02 0%	0.15 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bexagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	< 0.0001
	Comments	P-value is based on one sided statistical tests using a 0.025 level of significance.
	Method	Regression, Logistic
	Comments	Region, baseline HbA1c, background treatment, eGFR at baseline, treatment as a fixed effect covariate.
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.12
	Confidence Interval	(2-Sided) 95%; 0.05 to 0.28
	Parameter Dispersion	Type: Value:
	Estimation Comments	Odds ratio is calculated as the odds ratio of bexagliflozin over glimepiride.

5. Secondary Outcome

Title	Superiority of Bexagliflozin Over Glimepiride in HbA1c Reduction at Week 60.
Description	Superiority of bexagliflozin over glimepiride in HbA1c reduction from baseline to week 60 will be declared if the upper bound of 95% CI is less than 0.
Time Frame	Baseline to Week 60

Outcome Measure Data

Analysis Population Description

The intention-to-treat population was used for the analysis. Subjects with a value at baseline and at week 60 were analyzed.

Arm/Group Title	Bexagliflozin	Glimepiride
Arm/Group Description	Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for glimepiride for the duration of the study. Bexagliflozin tablets: 20 mg Glimepiride capsules: Placebo, inactive capsule to match the active comparator	Subjects will receive a glimepiride capsule, 2, 4 or 6 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. Bexagliflozin: Placebo, inactive tablet to match the active comparator Glimepiride capsules: 2, 4 or 6 mg
Measure Participants	193	191
Least Squares Mean (Standard Error) [percentage of glycated hemoglobin]	-0.70 (0.058)	-0.66 (0.058)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Bexagliflozin, Glimepiride
	Comments
	Type of Statistical Test	Superiority
	Comments	Superiority of bexagliflozin over glimepiride in HbA1c reduction from baseline to week 60 will be declared if the upper bound of 95% confidence interval is less than 0
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference of LS Means
	Estimated Value	-0.05
	Confidence Interval	(2-Sided) 95%; -0.21 to 0.11
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse event data was collected from Week -8 (V2, wash-out) to Week 98 (V18, follow-up).
Arm/Group Title	Bexagliflozin		Glimepiride
Arm/Group Description	Subjects will receive a bexagliflozin tablet, 20 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for glimepiride for the duration of the study. Bexagliflozin tablets: 20 mg Glimepiride capsules: Placebo, inactive capsule to match the active comparator		Subjects will receive a glimepiride capsule, 2, 4 or 6 mg, once daily for the duration of the study. Subjects will continue taking metformin and receive placebo for bexagliflozin for the duration of the study. Bexagliflozin: Placebo, inactive tablet to match the active comparator Glimepiride capsules: 2, 4 or 6 mg
All Cause Mortality
	Bexagliflozin		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/213 (0%)		1/213 (0.5%)
Serious Adverse Events
	Bexagliflozin		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	25/213 (11.7%)		26/213 (12.2%)
Cardiac disorders
Acute myocardial infarction	2/213 (0.9%)		1/213 (0.5%)
Myocardial ischemia	1/213 (0.5%)		2/213 (0.9%)
Acute coronary syndrome	1/213 (0.5%)		1/213 (0.5%)
Angina unstable	0/213 (0%)		1/213 (0.5%)
Bradycardia	0/213 (0%)		1/213 (0.5%)
Cardiac failure congestive	0/213 (0%)		1/213 (0.5%)
Myocardial infarction	0/213 (0%)		1/213 (0.5%)
Myocarditis	1/213 (0.5%)		0/213 (0%)
Palpitation	1/213 (0.5%)		0/213 (0%)
Congenital, familial and genetic disorders
Phimosis	1/213 (0.5%)		0/213 (0%)
Ear and labyrinth disorders
Deafness unilateral	0/213 (0%)		1/213 (0.5%)
Eye disorders
Ectropion	1/213 (0.5%)		0/213 (0%)
Entropion	1/213 (0.5%)		0/213 (0%)
Retinal detachment	0/213 (0%)		1/213 (0.5%)
Gastrointestinal disorders
Faecaloma	1/213 (0.5%)		0/213 (0%)
Inguinal hernia	1/213 (0.5%)		0/213 (0%)
Small intestinal obstruction	0/213 (0%)		1/213 (0.5%)
General disorders
Non-cardiac chest pain	1/213 (0.5%)		0/213 (0%)
Hepatobiliary disorders
Cholelithiasis	1/213 (0.5%)		1/213 (0.5%)
Infections and infestations
Pneumonia	2/213 (0.9%)		2/213 (0.9%)
Erysipelas	0/213 (0%)		1/213 (0.5%)
Otitis media chronic	0/213 (0%)		1/213 (0.5%)
Pyelonephritis acute	1/213 (0.5%)		0/213 (0%)
Metabolism and nutrition disorders
Hyponatremia	0/213 (0%)		1/213 (0.5%)
Musculoskeletal and connective tissue disorders
Osteoarthritis	1/213 (0.5%)		1/213 (0.5%)
Osteochondrosis	0/213 (0%)		1/213 (0.5%)
Polyarthritis	1/213 (0.5%)		0/213 (0%)
Spinal osteoarthritis	1/213 (0.5%)		0/213 (0%)
Ankle fracture	0/213 (0%)		1/213 (0.5%)
Contusion	1/213 (0.5%)		0/213 (0%)
Muscle rupture	1/213 (0.5%)		0/213 (0%)
Tibia fracture	0/213 (0%)		1/213 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal adenocarcinoma	1/213 (0.5%)		0/213 (0%)
Small cell lung cancer	0/213 (0%)		1/213 (0.5%)
Nervous system disorders
Transient ischemic attack	1/213 (0.5%)		1/213 (0.5%)
Carotid artery stenosis	1/213 (0.5%)		0/213 (0%)
Cerebrovascular accident	1/213 (0.5%)		0/213 (0%)
Ischemic stroke	0/213 (0%)		1/213 (0.5%)
Nervous system disorder	0/213 (0%)		1/213 (0.5%)
Thalamic infarction	1/213 (0.5%)		0/213 (0%)
Renal and urinary disorders
Nephrolithiasis	0/213 (0%)		2/213 (0.9%)
Bladder disorder	0/213 (0%)		1/213 (0.5%)
Reproductive system and breast disorders
Genital hemorrhage	0/213 (0%)		1/213 (0.5%)
Uterine prolapse	1/213 (0.5%)		0/213 (0%)
Skin and subcutaneous tissue disorders
Dermatitis	0/213 (0%)		1/213 (0.5%)
Ecchymosis	0/213 (0%)		1/213 (0.5%)
Vascular disorders
Arterial occlusive disease	0/213 (0%)		1/213 (0.5%)
Other (Not Including Serious) Adverse Events
	Bexagliflozin		Glimepiride
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	98/213 (46%)		112/213 (52.6%)
Infections and infestations
Nasopharyngitis	29/213 (13.6%)		29/213 (13.6%)
Urinary Tract Infection	25/213 (11.7%)		10/213 (4.7%)
Bronchitis	14/213 (6.6%)		16/213 (7.5%)
Metabolism and nutrition disorders
Hypoglycemia	36/213 (16.9%)		71/213 (33.3%)
Diabetes mellitus inadequate control	1/213 (0.5%)		17/213 (8%)
Musculoskeletal and connective tissue disorders
Back pain	6/213 (2.8%)		16/213 (7.5%)
Arthralgia	13/213 (6.1%)		4/213 (1.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Investigator has no publication right.