Type 2 Diabetes Mellitus
Conditions
Brief summary
Primary Objective: To demonstrate the non-inferiority of Sotagliflozin 400 milligrams (mg) compared to Glimepiride on hemoglobin A1c (HbA1c) reduction at Week 52 in participants with Type 2 Diabetes (T2D) who have inadequate glycemic control with metformin. Secondary Objectives: To demonstrate the superiority of Sotagliflozin 400 mg compared to Glimepiride on change in body weight, systolic blood pressure (SBP) in participants with baseline SBP ≥130 millimeter of mercury (mmHg), SBP in all participants, and proportion of participants with at least 1 documented symptomatic hypoglycemic event (≤70 milligrams per deciliter \[mg/dL\]). * To demonstrate the superiority of Sotagliflozin 400 mg compared to placebo on change in HbA1c, body weight, SBP in participants with baseline SBP ≥130 mmHg, SBP in all participants. * To demonstrate the superiority of Sotagliflozin 200 mg compared to placebo on change in HbA1c. * To demonstrate the non-inferiority of Sotagliflozin 400 mg compared to Glimepiride on change in HbA1c. * To demonstrate the superiority of Sotagliflozin 400 mg compared to Glimepiride on change in HbA1c. * To evaluate the safety and tolerability of Sotagliflozin compared to Glimepiride and placebo.
Detailed description
Up to 58 weeks, including a Screening Period consisting of a Screening phase of up to 2 weeks, a 2-week single-blind placebo Run-in phase, a 52-week double-blind Treatment Period, and a 2-week post-treatment Follow-up period to collect safety information.
Interventions
Pharmaceutical form: tablet Route of administration: oral
DRUGGlimepiride
Pharmaceutical form: capsule Route of administration: oral
DRUGMetformin
Pharmaceutical form: tablet Route of administration: oral
DRUGPlacebo
Pharmaceutical form: tablet Route of administration: oral
Sponsors
Sanofi
Lexicon Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
: * Participants with Type 2 Diabetes (T2D) treated with metformin at a stable dose ≥1500 milligrams per day (mg/day) or maximum tolerated dose (documented) for at least 12 weeks prior to Screening Visit; in case of documented lack of tolerance, metformin dose \<1500 mg/day is acceptable, and the dose should be stable for at least 12 weeks prior to Screening Visit. * Participants has given written informed consent to participate in the study in accordance with local regulations.
Exclusion criteria
* Age \<18 years at the Screening Visit or \<legal age of majority, whichever is greater. * Type 1 diabetes mellitus. * HbA1c, HbA1c \<7.0% or HbA1c \>10% at Screening. * Fasting Plasma Glucose (FPG) \>15 millimoles per liter (mmol/L) (\>270 milligram per deciliter \[mg/dL\]) measured by the central laboratory at Screening (Visit 1) and confirmed by a repeat test (\>15 mmol/L \[\>270 mg/dL\]) before randomization. * Body mass index ≤20 or \>45 kilogram per meter square (kg/m\^2) at Screening. * Pregnant (confirmed by pregnancy test at the Screening) or breast-feeding women. * Women of childbearing potential (WOCBP) not willing to use highly effective method(s) of birth control during the study treatment period and the follow-up period, or who are unwilling or unable to be tested for pregnancy (see Appendix A) during the study. * Previous use of any antidiabetic drug other than Metformin within 12 weeks preceding the Screening Visit. * Use of a selective Sodium-glucose co-transporter-2 (SGLT2) inhibitor (e.g., Canagliflozin, Dapagliflozin, or Empagliflozin) within 3 months prior to the Screening visit. * Use of systemic glucocorticoids (excluding topical, or ophthalmic application, intra-articular, nasal spray or inhaled forms) for more than 10 consecutive days within 90 days prior to the Screening Visit. * Previous insulin use \>1 month (at any time, except for treatment of gestational diabetes). * History of prior gastric surgical procedure, including gastric banding, or inflammatory bowel disease within 3 years prior to the Screening Visit. * Difficulty swallowing such that the participants cannot take the investigational medicinal product (IMP). * History of diabetic ketoacidosis or nonketotic hyperosmolar coma within 12 weeks prior to the Screening Visit. * Mean of 3 separate blood pressure measurements \>180 millimeter of mercury (mmHg) (SBP) or \>100 mmHg (DBP). * History of hypertensive emergency within 12 weeks prior to Screening. * Participants who have previously been randomized in any clinical trial of Sotagliflozin/LX4211. * Participants with severe renal disease as defined by an estimated glomerular filtration rate (eGFR) of \<30 milliliter per minute per meter square (mL/min/1.73 m\^2) at Screening, based on the 4 variable Modification of Diet in Renal Disease (MDRD) equation (or according to the renal function restrictions of metformin use defined in the local approved label). * Participants with severe anemia, severe cardiovascular (including congestive heart failure New York Heart Association IV), respiratory, hepatic, neurological, psychiatric, or active malignant tumor or other major systemic disease that, according to Investigator, will preclude their safe participation in this study, or will make implementation of the protocol or interpretation of the study results difficult. * Aspartate aminotransferase and/or alanine aminotransferase: \>3 times the upper limit of the normal laboratory range (ULN). * Total bilirubin: \>1.5 times ULN (except in case of Gilbert's syndrome). * Participants who have taken other investigational drugs within 12 weeks or 5 half-lives from Screening whichever is longer. * Participants unwilling or unable to perform self-monitoring blood glucose (SMBG), complete the participant diary, or comply with study visits and other study procedures as required per protocol. * Participants with contraindication to glimepiride as per local labelling. * Participants with contraindication to metformin as per local labelling. The above information is not intended to contain all considerations relevant to a Participants potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c at Week 52 | Baseline, Week 52 | An analysis of covariance (ANCOVA) model was used for the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1c at Week 26 | Baseline, Week 26 | An ANCOVA model was used for the analysis. |
| Change From Baseline in Body Weight at Week 26 and 52 | Baseline, Week 26, Week 52 | An ANCOVA model was used for the analysis. |
| Change From Baseline in Systolic Blood Pressure (SBP) for Participants With SBP ≥130 mmHg at Week 12 | Baseline, Week 12 | An ANCOVA model was used for the analysis. |
| Percentage of Participants With At Least One Documented Symptomatic Hypoglycemic Event | Up to Week 52 | Documented symptomatic hypoglycemia includes the typical symptoms of hypoglycemia (increased sweating, nervousness, asthenia/weakness, tremor, dizziness, increased appetite, palpitations, headache, sleep disorder, confusion, seizures, unconsciousness, and/or coma) and plasma glucose ≤ 70 mg/dL (3.9 mmol/L). |
| Percentage of Participants With Adverse Events (AEs) | Up to Week 52 | An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. |
| Change From Baseline in Systolic Blood Pressure (SBP) for All Participants at Week 12 | Baseline, Week 12 | An ANCOVA model was used for the analysis. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Hypoglycemic Events | Up to Week 52 | Percentage of participants with hypoglycemic events are reported for the following 3 categories: Any hypoglycemia (as reported in the Electronic Case Report Form); Documented symptomatic hypoglycemia \[typical symptoms of hypoglycemia (increased sweating, nervousness, asthenia/weakness, tremor, dizziness, increased appetite, palpitations, headache, sleep disorder, confusion, seizures, unconsciousness, and/or coma) and plasma glucose ≤ 70 mg/dL (3.9 mmol/L)\]; Severe \[an event requiring assistance of another person to actively administer carbohydrate, glucagon, intravenous glucose or other resuscitative actions\] or documented symptomatic hypoglycemia \[typical symptoms of hypoglycemia and plasma glucose ≤ 70 mg/dL\]. |
Countries
Bulgaria, Hungary, Slovakia, United States
Participant flow
Recruitment details
Participants took part in the study at 138 investigative sites in United States, Bulgaria, Hungary, and Slovakia from 01 December 2017 to 06 September 2019.
Pre-assignment details
Participants with diagnosis of Type 2 Diabetes Mellitus were enrolled in 1 of 4 treatment groups: Placebo or Sotagliflozin 200 mg or Sotagliflozin 400 mg or Glimepiride. Participants were randomly assigned in the ratio of 1:1:2:2 to these reporting groups. Total of 954 participants were enrolled in study, out of which 952 were randomized and treated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks. | 159 |
| Sotagliflozin 400 mg Following a 2-week run-in period, two Sotagliflozin 200 mg, tablets, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks. | 317 |
| Sotagliflozin 200 mg Following a 2-week run-in period, one Sotagliflozin 200 mg, tablet and one Sotagliflozin-matching placebo tablet, and two Glimepiride-matching placebo capsules, taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks. | 160 |
| Glimepiride Following a 2-week run-in period, two Sotagliflozin-matching placebo tablets, and combination of two Glimepiride capsules with adequate dose strengths per dose titration (titrated up to 6mg), taken orally once daily before the first meal of the day in the double-blind treatment period up to 52 weeks. | 318 |
| Total | 954 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 4 | 1 | 3 |
| Overall Study | At the Participant's own request | 20 | 26 | 14 | 23 |
| Overall Study | Lost to Follow-up | 2 | 2 | 1 | 2 |
| Overall Study | Poor Compliance to Protocol | 0 | 1 | 0 | 1 |
| Overall Study | Reason Not Specified | 6 | 18 | 16 | 19 |
Baseline characteristics
| Characteristic | Total | Glimepiride | Sotagliflozin 200 mg | Sotagliflozin 400 mg | Placebo |
|---|---|---|---|---|---|
| Age, Continuous | 59.4 years STANDARD_DEVIATION 10.2 | 59.8 years STANDARD_DEVIATION 9.6 | 58.6 years STANDARD_DEVIATION 9.9 | 59.7 years STANDARD_DEVIATION 10.4 | 58.8 years STANDARD_DEVIATION 11.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 297 Participants | 111 Participants | 53 Participants | 85 Participants | 48 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 653 Participants | 207 Participants | 106 Participants | 230 Participants | 110 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 0 Participants | 1 Participants | 2 Participants | 1 Participants |
| Hemoglobin A1c (HbA1c) | 8.09 percentage of HbA1c STANDARD_DEVIATION 0.79 | 8.07 percentage of HbA1c STANDARD_DEVIATION 0.79 | 8.11 percentage of HbA1c STANDARD_DEVIATION 0.86 | 8.09 percentage of HbA1c STANDARD_DEVIATION 0.78 | 8.12 percentage of HbA1c STANDARD_DEVIATION 0.73 |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 15 Participants | 4 Participants | 3 Participants | 5 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 102 Participants | 36 Participants | 19 Participants | 34 Participants | 13 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 4 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 0 Participants | 0 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) White | 823 Participants | 277 Participants | 136 Participants | 269 Participants | 141 Participants |
| Region of Enrollment Bulgaria | 45 participants | 16 participants | 5 participants | 17 participants | 7 participants |
| Region of Enrollment Hungary | 136 participants | 42 participants | 24 participants | 48 participants | 22 participants |
| Region of Enrollment Slovakia | 80 participants | 30 participants | 10 participants | 28 participants | 12 participants |
| Region of Enrollment United States | 693 participants | 230 participants | 121 participants | 224 participants | 118 participants |
| Sex: Female, Male Female | 452 Participants | 143 Participants | 75 Participants | 157 Participants | 77 Participants |
| Sex: Female, Male Male | 502 Participants | 175 Participants | 85 Participants | 160 Participants | 82 Participants |
| Systolic Blood Pressure (SBP) | 133.61 millimeter of mercury (mmHg) STANDARD_DEVIATION 14.3 | 134.66 millimeter of mercury (mmHg) STANDARD_DEVIATION 14.43 | 132.78 millimeter of mercury (mmHg) STANDARD_DEVIATION 13.29 | 133.17 millimeter of mercury (mmHg) STANDARD_DEVIATION 14.37 | 133.23 millimeter of mercury (mmHg) STANDARD_DEVIATION 14.9 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 159 | 1 / 317 | 0 / 159 | 2 / 317 |
| other Total, other adverse events | 30 / 159 | 49 / 317 | 21 / 159 | 22 / 317 |
| serious Total, serious adverse events | 11 / 159 | 17 / 317 | 11 / 159 | 14 / 317 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1c at Week 52
An analysis of covariance (ANCOVA) model was used for the analysis.
Time frame: Baseline, Week 52
Population: Intend to treat (ITT) population included all randomized participants. Missing data are imputed using the retrieved dropouts imputation method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hemoglobin A1c at Week 52 | -0.40 percentage of HbA1c | Standard Error 0.187 |
| Sotagliflozin 400 mg | Change From Baseline in Hemoglobin A1c at Week 52 | -0.65 percentage of HbA1c | Standard Error 0.101 |
| Sotagliflozin 200 mg | Change From Baseline in Hemoglobin A1c at Week 52 | -0.49 percentage of HbA1c | Standard Error 0.114 |
| Glimepiride | Change From Baseline in Hemoglobin A1c at Week 52 | -0.61 percentage of HbA1c | Standard Error 0.093 |
Comparison: The change from baseline to Week 52 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at screening, randomization strata of SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline HbA1c as a covariate.p-value: 0.330695% CI: [-0.12, 0.357]ANCOVA
Comparison: The change from baseline to Week 52 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at screening, randomization strata of SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline HbA1c as a covariate.p-value: 0.711295% CI: [-0.265, 0.181]ANCOVA
Secondary
Change From Baseline in Body Weight at Week 26 and 52
An ANCOVA model was used for the analysis.
Time frame: Baseline, Week 26, Week 52
Population: ITT population included all randomized participants. Missing data are imputed using the retrieved dropouts \& washout imputation method.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline in Body Weight at Week 26 and 52 | Change at Week 26 | -1.26 kilogram (kg) | Standard Error 0.329 |
| Placebo | Change From Baseline in Body Weight at Week 26 and 52 | Change at Week 52 | -0.47 kilogram (kg) | Standard Error 1.406 |
| Sotagliflozin 400 mg | Change From Baseline in Body Weight at Week 26 and 52 | Change at Week 52 | -2.64 kilogram (kg) | Standard Error 0.503 |
| Sotagliflozin 400 mg | Change From Baseline in Body Weight at Week 26 and 52 | Change at Week 26 | -2.75 kilogram (kg) | Standard Error 0.257 |
| Sotagliflozin 200 mg | Change From Baseline in Body Weight at Week 26 and 52 | Change at Week 52 | -1.74 kilogram (kg) | Standard Error 0.707 |
| Sotagliflozin 200 mg | Change From Baseline in Body Weight at Week 26 and 52 | Change at Week 26 | -2.24 kilogram (kg) | Standard Error 0.336 |
| Glimepiride | Change From Baseline in Body Weight at Week 26 and 52 | Change at Week 52 | 0.94 kilogram (kg) | Standard Error 0.452 |
| Glimepiride | Change From Baseline in Body Weight at Week 26 and 52 | Change at Week 26 | 0.70 kilogram (kg) | Standard Error 0.256 |
Comparison: The change from baseline to Week 26 is analyzed using ANCOVA model with treatment groups (placebo, sotagliflozin 200 mg, sotagliflozin 400 mg, glimepiride), randomization strata of HbA1c (≤ 8.5, \>8.5%) at screening, randomization strata of SBP (\<130,≥ 130 mmHg) at screening, and country as fixed effects, and baseline body weight as a covariate.p-value: <0.000195% CI: [-2.173, -0.803]ANCOVA
Comparison: The change from baseline to Week 52 is analyzed using analysis of ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at screening, randomization strata of SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects and baseline body weight as a covariate.p-value: <0.000195% CI: [-4.651, -2.517]ANCOVA
Secondary
Change From Baseline in Hemoglobin A1c at Week 26
An ANCOVA model was used for the analysis.
Time frame: Baseline, Week 26
Population: ITT population included all randomized participants. Missing data are imputed using the washout imputation method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Hemoglobin A1c at Week 26 | -0.41 percentage of HbA1c | Standard Error 0.097 |
| Sotagliflozin 400 mg | Change From Baseline in Hemoglobin A1c at Week 26 | -0.77 percentage of HbA1c | Standard Error 0.076 |
| Sotagliflozin 200 mg | Change From Baseline in Hemoglobin A1c at Week 26 | -0.61 percentage of HbA1c | Standard Error 0.098 |
| Glimepiride | Change From Baseline in Hemoglobin A1c at Week 26 | -1.02 percentage of HbA1c | Standard Error 0.075 |
Comparison: The change from baseline to Week 26 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at screening, randomization strata of SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline HbA1c as a covariate.p-value: 0.082795% CI: [-0.44, 0.027]ANCOVA
Comparison: The change from baseline to Week 26 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at screening, randomization strata of SBP (\<130, ≥130 mmHg) at screening, and country as fixed effects, and baseline HbA1c as a covariate.p-value: 0.000395% CI: [-0.571, -0.167]ANCOVA
Secondary
Change From Baseline in Systolic Blood Pressure (SBP) for All Participants at Week 12
An ANCOVA model was used for the analysis.
Time frame: Baseline, Week 12
Population: ITT population included all randomized participants. Missing data are imputed using washout imputation method under the missing not at random framework.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) for All Participants at Week 12 | -2.64 mmHg | Standard Error 1.013 |
| Sotagliflozin 400 mg | Change From Baseline in Systolic Blood Pressure (SBP) for All Participants at Week 12 | -4.70 mmHg | Standard Error 0.791 |
| Sotagliflozin 200 mg | Change From Baseline in Systolic Blood Pressure (SBP) for All Participants at Week 12 | -4.77 mmHg | Standard Error 1.033 |
| Glimepiride | Change From Baseline in Systolic Blood Pressure (SBP) for All Participants at Week 12 | -0.68 mmHg | Standard Error 0.795 |
Comparison: The change from baseline to Week 12 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤ 8.5, \>8.5%) at screening, and country as fixed effects, and baseline SBP as a covariate.p-value: <0.000195% CI: [-5.73, -2.319]ANCOVA
Secondary
Change From Baseline in Systolic Blood Pressure (SBP) for Participants With SBP ≥130 mmHg at Week 12
An ANCOVA model was used for the analysis.
Time frame: Baseline, Week 12
Population: Analysis was performed on ITT population in participants with baseline SBP ≥130 mmHg. Missing data are imputed using washout imputation method.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Systolic Blood Pressure (SBP) for Participants With SBP ≥130 mmHg at Week 12 | -5.34 mmHg | Standard Error 1.451 |
| Sotagliflozin 400 mg | Change From Baseline in Systolic Blood Pressure (SBP) for Participants With SBP ≥130 mmHg at Week 12 | -8.03 mmHg | Standard Error 1.064 |
| Sotagliflozin 200 mg | Change From Baseline in Systolic Blood Pressure (SBP) for Participants With SBP ≥130 mmHg at Week 12 | -9.12 mmHg | Standard Error 1.466 |
| Glimepiride | Change From Baseline in Systolic Blood Pressure (SBP) for Participants With SBP ≥130 mmHg at Week 12 | -3.86 mmHg | Standard Error 1.081 |
Comparison: The change from baseline to Week 12 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at screening, and country as fixed effects, and baseline SBP as a covariate.p-value: 0.001295% CI: [-6.701, -1.65]ANCOVA
Comparison: The change from baseline to Week 12 is analyzed using ANCOVA model with treatment groups, randomization strata of HbA1c (≤8.5, \>8.5%) at screening, and country as fixed effects, and baseline SBP as a covariate.p-value: 0.097395% CI: [-5.89, 0.491]ANCOVA
Secondary
Percentage of Participants With Adverse Events (AEs)
An AE is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment.
Time frame: Up to Week 52
Population: Safety population included all participants who had received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With Adverse Events (AEs) | 57.2 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Adverse Events (AEs) | 59.9 percentage of participants |
| Sotagliflozin 200 mg | Percentage of Participants With Adverse Events (AEs) | 56.6 percentage of participants |
| Glimepiride | Percentage of Participants With Adverse Events (AEs) | 49.2 percentage of participants |
Secondary
Percentage of Participants With At Least One Documented Symptomatic Hypoglycemic Event
Documented symptomatic hypoglycemia includes the typical symptoms of hypoglycemia (increased sweating, nervousness, asthenia/weakness, tremor, dizziness, increased appetite, palpitations, headache, sleep disorder, confusion, seizures, unconsciousness, and/or coma) and plasma glucose ≤ 70 mg/dL (3.9 mmol/L).
Time frame: Up to Week 52
Population: ITT population included all randomized participants.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants With At Least One Documented Symptomatic Hypoglycemic Event | 0.63 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With At Least One Documented Symptomatic Hypoglycemic Event | 1.26 percentage of participants |
| Sotagliflozin 200 mg | Percentage of Participants With At Least One Documented Symptomatic Hypoglycemic Event | 3.75 percentage of participants |
| Glimepiride | Percentage of Participants With At Least One Documented Symptomatic Hypoglycemic Event | 16.67 percentage of participants |
Comparison: Weighted average of percentage difference between treatment groups from each stratum \[randomization strata of HbA1c \[≤8.5%, \>8.5%\] at screening, randomization strata of mean SBP \[\<130, ≥130 mmHg\] at screening using Cochran-Mantel-Haenszel weights.p-value: <0.000195% CI: [-19.67, -11.12]Cochran-Mantel-Haenszel
Other Pre-specified
Percentage of Participants With Hypoglycemic Events
Percentage of participants with hypoglycemic events are reported for the following 3 categories: Any hypoglycemia (as reported in the Electronic Case Report Form); Documented symptomatic hypoglycemia \[typical symptoms of hypoglycemia (increased sweating, nervousness, asthenia/weakness, tremor, dizziness, increased appetite, palpitations, headache, sleep disorder, confusion, seizures, unconsciousness, and/or coma) and plasma glucose ≤ 70 mg/dL (3.9 mmol/L)\]; Severe \[an event requiring assistance of another person to actively administer carbohydrate, glucagon, intravenous glucose or other resuscitative actions\] or documented symptomatic hypoglycemia \[typical symptoms of hypoglycemia and plasma glucose ≤ 70 mg/dL\].
Time frame: Up to Week 52
Population: Safety population included all randomized participants who received at least 1 dose of double-blind investigational medicinal product (IMP) (regardless of the amount of treatment administered).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo | Percentage of Participants With Hypoglycemic Events | Any hypoglycemia | 2.5 percentage of participants |
| Placebo | Percentage of Participants With Hypoglycemic Events | Severe or documented symptomatic hypoglycemia | 0.6 percentage of participants |
| Placebo | Percentage of Participants With Hypoglycemic Events | Documented symptomatic hypoglycemia | 0.6 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events | Any hypoglycemia | 4.1 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events | Severe or documented symptomatic hypoglycemia | 1.3 percentage of participants |
| Sotagliflozin 400 mg | Percentage of Participants With Hypoglycemic Events | Documented symptomatic hypoglycemia | 1.3 percentage of participants |
| Sotagliflozin 200 mg | Percentage of Participants With Hypoglycemic Events | Documented symptomatic hypoglycemia | 3.8 percentage of participants |
| Sotagliflozin 200 mg | Percentage of Participants With Hypoglycemic Events | Any hypoglycemia | 6.3 percentage of participants |
| Sotagliflozin 200 mg | Percentage of Participants With Hypoglycemic Events | Severe or documented symptomatic hypoglycemia | 3.8 percentage of participants |
| Glimepiride | Percentage of Participants With Hypoglycemic Events | Any hypoglycemia | 25.9 percentage of participants |
| Glimepiride | Percentage of Participants With Hypoglycemic Events | Severe or documented symptomatic hypoglycemia | 16.7 percentage of participants |
| Glimepiride | Percentage of Participants With Hypoglycemic Events | Documented symptomatic hypoglycemia | 16.7 percentage of participants |