Obesity, Type 1 Diabetes
Conditions
Keywords
Type 1 diabetes, Obesity, HbA1c, Time-in-range, Weight loss, Cardiovascular risk
Brief summary
The purpose of this study is to assess the use of once weekly semaglutide injection in inadequately controlled obese adults with type 1 diabetes (T1D) using FDA-approved hybrid closed-loop therapies.
Detailed description
After being informed about the study and potential risks, all patients given written informed consent will undergo a 2-week screening period to determine eligibility for study entry. At week 0, patients who meet the eligibility requirements will be randomized in a double-blind manner using computer generated randomization scheme to receive either semaglutide or placebo (1:1 ratio) for 26 weeks.
Interventions
DRUGSemaglutide
Semaglutide up to 1 mg per week in addition to standard closed-loop therapy
DRUGPlacebo
Injection placebo up to 1 mg per week in addition to standard closed-loop therapy
Sponsors
Juvenile Diabetes Research Foundation
Viral N. Shah
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 65 Years
Healthy volunteers
No
Inclusion criteria
For an eligible subject, all inclusion criteria must be answered yes 1. Age ≥18 and ≤ 65 years 2. Patients with clinical diagnosis of T1D diagnosed for at least 12 months 3. Patient is on FDA- approved hybrid closed-loop system for ≥ 3 months 4. Willing to use once weekly semaglutide 5. Willing to share devices (HCL system) data uploads 6. HbA1c \>7.0% and \<10.0% 7. Body mass index ≥30 kg/m2 8. Has current glucagon product to treat severe hypoglycemia 9. Has current ketone meters to check ketones 10. Ability to provide informed consent before any trial-related activities
Exclusion criteria
1. Age \<18 years and \>65 years 2. HbA1c ≤7.0 % or ≥ 10.0% at screening 3. Less than 12 months of insulin treatment 4. Use of unapproved insulin for HCL system. E.g. use of Fiasp in the Tandem Control-IQ system 5. Not willing to share the devices (HCL system) data uploads 6. Non compatible devices (e.g. pump, CGM or smart phones) for data transfer 7. Current use of multiple daily injection or inhaled insulin (Afrezza) 8. Patients with T1D using any glucose lowering medications other than insulin at the time of screening 9. Pregnancy, breast feeding, and positive pregnancy test during screening 10. Women of childbearing age wanting to become pregnant 11. Unwilling to use acceptable contraceptive methods (for both men and women) during the trial period 12. Current use (≥ 2 weeks of continuous use) of any steroidal medication, or anticipated long-term steroidal treatment (\>4 weeks continuously), during the study period 13. Use of GLP-1RA or weight loss medications in the past 3 month 14. Clinical diagnosis/history of gastroparesis or gastric motility disorders 15. Serum triglycerides \>500 mg/dL 16. Planning for bariatric surgery during the study period 17. eGFR below 45 ml/min/1.73 m\^2 using CKD-EPI formula 18. History of severe hypoglycemia in the previous 3 months 19. History of diabetic ketoacidosis requiring hospitalization in the past 3 months 20. History of allergy to any form of insulin, GLP-1RA or its excipients 21. History of any form of pancreatitis 22. History of stroke, myocardial infarction in the past 3 months 23. History of congestive heart failure class III or IV 24. History of acute or chronic liver disease 25. History of malignancy requiring chemotherapy, surgery or radiation in previous 5 years 26. Personal or family history of multiple endocrine neoplasia type 2 (MEN-2) or familial thyroid carcinoma or non-familial medullary thyroid carcinoma 27. Have a pacemaker, metal implants, or aneurysm clips or weigh \>330 lbs (exclusion only if doing MRI) 28. Use of investigational drugs within 5 half-lives prior to screening 29. Participation to other intervention trials during the study period 30. Any comorbidities or medical conditions such as severe psychiatric disorder that make a person unfit for the study at the discretion of the investigators
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Adults With T1D Achieving Composite Outcome (CGM-measured Time in Range (TIR)>70% With Time Below Range (TBR) of <4% and Reduction in Body Weight by 5%) at 26 Weeks in the Semaglutide Group Compared to Placebo Group | 26 weeks | Primary outcome will be analyzed per statistical analysis plan using intention to treat basis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Mean Glucose | 26 weeks | Mean glucose (mg/dL) will be obtained by CGM and change in mean CGM glucose from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis. |
| Percent Time Spent in CGM-measured Glucose Range of 70-140 mg/dL (Time in Tight Target Range; TTIR) | 26 weeks | Percent of time spent in tight glucose range (70-140 mg/dL) will be obtained by CGM and change in percent time in range from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis. |
| Percent Time Spent in CGM-measured Glucose >180 mg/dL | 26 weeks | Percent of time spent in glucose range \>180 mg/dL will be obtained by CGM and change in mean CGM glucose from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis. |
| Percent Time Spent in CGM-measured Glucose >250mg/dL | 26 weeks | Percent of time spent in glucose range \>250 mg/dL will be obtained by CGM and change in mean CGM glucose from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis. |
| Change in HbA1c | 26 weeks | HbA1c will be measured at a central laboratory and change in Hba1c from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis. |
| Change in CGM Measured Glycemic Variability (Coefficient of Variation) | 26 weeks | Glucose coefficient of variation (mg/dL) will be obtained by CGM and change in glucose CV from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis. |
| Change in Weight | 26 weeks | The change in kg of body weight from baseline to 26 weeks will be compared by randomization group using an ITT analysis. |
| Change in BMI (Kg/m2) | 26 weeks | Change in body mass index (BMI) calculated as kg body weight per meter squared of height from baseline to 26 weeks will be compared by randomization group using an ITT analysis. |
| Severe Hypoglycemia | 26 weeks | SH events in number of patients per group |
| Percent Time Spent in CGM-measured Glucose <70mg/dL | 26 weeks | Percent of time spent in glucose range \<70 mg/dL will be obtained by CGM and change in mean CGM glucose from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of TBR<70 Events | 26 weeks | Numbers of events of CGM glucose \<70 mg/dL lasting for at least 15 minutes between two groups |
| Number of TBR <54 Events | 26 weeks | Numbers of events of CGM glucose \<54mg/dL lasting for at least 15 minutes between two groups |
| Change in Total Daily Dose of Insulin (TDD, Units Per Day and U/Kg/Day) | 26 weeks | Change in TDD between two groups |
| Proportion Achieving Weight Loss ≥5% | 26 weeks | Proportion of participants achieving weight loss ≥5% from baseline between two groups |
| Proportion Achieving Weight Loss ≥10% | 26 weeks | Proportion of participants achieving weight loss ≥10% from baseline between two groups |
| Proportion of Achieving BMI <30 kg/m2 | 26 weeks | Proportion of participants achieving BMI \<30 kg/m2 between two groups |
| Proportion of Achieving BMI <25 kg/m2 | 26 weeks | Proportion of participants achieving BMI \<25 kg/m2 between two groups |
| Change in Systolic Blood Pressure (SBP) | 26 weeks | change in SBP (mmHg) between two groups |
| Change in Diastolic Blood Pressure (DBP) | 26 weeks | change in DBP (mmHg) between two groups |
| Change in Pulse Pressure | 26 weeks | change in pulse pressure between two groups |
| Change in Triglyceride/HDL Ratio | 26 weeks | Change in triglyceride/HDL ratio between two groups |
| Change in Brach D | 26 weeks | Change in brachial arterial distensibility between two groups |
| Change in Carotid Intima Media Thickness (cIMT) | 26 weeks | Change in carotid intima media thickness (cIMT) between two groups |
| Change in Femoral to Carotid Pulse Wave Velocity (m/s) | 26 weeks | Change in femoral to carotid pulse wave velocity (m/s) between two groups |
| Change in Urine Albumin to Creatinine Ratio (ACR) | 26 weeks | Change in ACR between two groups |
| Quality of Life (Diabetes Dependent QOL) | 26 weeks | Change in QOL between two groups |
| Change in CGM Metrics by Daytime vs Nighttime | 26 weeks | Change in CGM metrics (TIR, TITR, mean glucose, TBR, TAR \>180, SD, CV) by daytime (6 AM to \<11 PM) and nighttime (11 PM to \<6 AM) between two groups |
| AID Setting Adjustment | 26 weeks | Defined any adjustment in settings by provider or patient per person over the study period by two groups (number of adjustments (N) during trial) between two groups |
| Achievement of Primary Outcome and Key Secondary Outcomes by Types of AID Systems | 26 weeks | Proportion of participants achieving primary outcome and key secondary glycemic outcomes by types of AID systems |
| Change in Carbohydrate Intake Per Day (Grams/Day) | 26 weeks | Change in Carbohydrate intake per day (grams/day) between two groups |
| Change in Total Bolus Insulin Per Day | 26 weeks | Change in total bolus insulin per day (units per day and U/Kg/day) between two groups |
| Change in eGFR | 26 weeks | Change in eGFR using CKD-EPI between two groups |
| Change in Basal Insulin Per Day | 26 weeks | Change in basal insulin per day (Total basal insulin including autobasal delivery, units per day and U/kg/day) between two groups |
| Change in HSI (Hepatic Steatosis Index) | 26 weeks | Change in HSI (hepatic steatosis index) between two groups |
| Change in MRI Measured Pulse Wave Velocity and Longitudinal Strain | 26 weeks | Change in MRI measured pulse wave velocity and longitudinal strain between two groups |
| Change in LDL-C | 26 weeks | Change in LDL-C between two groups |
| Change in TC | 26 weeks | Change in TC between two groups |
| Change in TG | 26 weeks | Change in TG between two groups |
| Change in HDL-C | 26 weeks | Change in HDL-C between two groups |
| Proportion With ACR <30 at 26 Weeks | 26 weeks | Proportion of participants with ACR \<30 at 26 weeks between two groups |
| Proportion With Change in ACR From >30 to <30 | 26 weeks | Proportion of participants with change in ACR from \>30 to \<30 between two groups |
| Achievement of Primary Outcomes by Baseline BMI (BMI <35 vs >35) | 26 weeks | Achievement of primary outcomes by baseline BMI (BMI \<35 vs \>35) |
| Achievement of Primary Outcomes by Baseline A1c (A1c <7.5% vs >7.5%) | 26 weeks | Achievement of primary outcomes by baseline A1c (A1c \<7.5% vs \>7.5%) |
| Change in Fib-4 Score | 26 weeks | Change in Fib-4 score between two groups |
| Change in Total Boluses Per Day | 26 weeks | Change in total boluses per day (frequency of boluses per day) between two groups |
| Change in Patient Reported Quality of Life | 26 weeks | Patient reported quality of life will be measured using a validated instrument (ADDQOL) and the change in score from baseline to 26 weeks will be compared by randomization group using an ITT analysis. |
| Proportion of Participants With HbA1c <7% | 26 weeks | proportion (N, %) of participants achieving HbA1c \<7% between two groups over 26 weeks |
| Proportion of Participants With HbA1c <7.5% | 26 weeks | proportion (N, %) of participants achieving HbA1c \<7.5% between two groups over 26 weeks |
| HbA1c Improvement | 26 weeks | HbA1c improvement from baseline to 26 weeks between two groups |
| HbA1c Improvement of >0.4% From Baseline | 26 weeks | proportion of participants with HbA1c improvement of \>0.4% from baseline between two groups |
| Proportion of Participants Achieving TIR >70% | 26 weeks | Proportion of participants achieving TIR \>70% between two groups over 26 weeks |
| Proportion of Participants Achieving TITR >50% | 26 weeks | Proportion of participants achieving TITR (time in 70-140 mg/dL) \>50% between two groups |
| Proportion of Participants Achieving TIR >80% | 26 weeks | Proportion of participants achieving TIR \>80% between two groups |
| Proportion of Participants Achieving TITR >60% | 26 weeks | Proportion of participants achieving TITR (time in 70-140 mg/dL) \>60% between two groups |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Semaglutide Participants in this group will receive semaglutide once weekly injection in addition to their standard closed-loop therapy
Semaglutide: Semaglutide up to 1 mg per week in addition to standard closed-loop therapy | 36 |
| Control Participants in this group will receive placebo once weekly injection in addition to their standard closed-loop therapy
Placebo: Injection placebo up to 1 mg per week in addition to standard closed-loop therapy | 36 |
| Total | 72 |
Baseline characteristics
| Characteristic | Semaglutide | Control | Total |
|---|---|---|---|
| Age, Continuous | 41.4 years STANDARD_DEVIATION 11.6 | 38.9 years STANDARD_DEVIATION 13.1 | 40 years STANDARD_DEVIATION 12 |
| body mass index | 34.7 kg/m2 STANDARD_DEVIATION 3.9 | 36.0 kg/m2 STANDARD_DEVIATION 5.2 | 35 kg/m2 STANDARD_DEVIATION 4.5 |
| Diabetes Duration | 23.4 years STANDARD_DEVIATION 11.2 | 21.9 years STANDARD_DEVIATION 11.6 | 23 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 4 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 35 Participants | 32 Participants | 67 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| HbA1c | 7.8 % STANDARD_DEVIATION 0.6 | 7.7 % STANDARD_DEVIATION 0.6 | 7.8 % STANDARD_DEVIATION 0.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 3 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 33 Participants | 30 Participants | 63 Participants |
| Sex: Female, Male Female | 22 Participants | 20 Participants | 42 Participants |
| Sex: Female, Male Male | 14 Participants | 16 Participants | 30 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 36 |
| other Total, other adverse events | 26 / 36 | 11 / 36 |
| serious Total, serious adverse events | 1 / 36 | 0 / 36 |
Outcome results
Primary
Proportion of Adults With T1D Achieving Composite Outcome (CGM-measured Time in Range (TIR)>70% With Time Below Range (TBR) of <4% and Reduction in Body Weight by 5%) at 26 Weeks in the Semaglutide Group Compared to Placebo Group
Primary outcome will be analyzed per statistical analysis plan using intention to treat basis.
Time frame: 26 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Semaglutide | Proportion of Adults With T1D Achieving Composite Outcome (CGM-measured Time in Range (TIR)>70% With Time Below Range (TBR) of <4% and Reduction in Body Weight by 5%) at 26 Weeks in the Semaglutide Group Compared to Placebo Group | 13 Participants |
| Control | Proportion of Adults With T1D Achieving Composite Outcome (CGM-measured Time in Range (TIR)>70% With Time Below Range (TBR) of <4% and Reduction in Body Weight by 5%) at 26 Weeks in the Semaglutide Group Compared to Placebo Group | 0 Participants |
Secondary
Change in BMI (Kg/m2)
Change in body mass index (BMI) calculated as kg body weight per meter squared of height from baseline to 26 weeks will be compared by randomization group using an ITT analysis.
Time frame: 26 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in BMI (Kg/m2) | -3.3 kg/m2 | Standard Error 0.3 |
| Control | Change in BMI (Kg/m2) | -0.2 kg/m2 | Standard Error 0.2 |
Secondary
Change in CGM Measured Glycemic Variability (Coefficient of Variation)
Glucose coefficient of variation (mg/dL) will be obtained by CGM and change in glucose CV from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.
Time frame: 26 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in CGM Measured Glycemic Variability (Coefficient of Variation) | -0.3 percentage | Standard Error 0.8 |
| Control | Change in CGM Measured Glycemic Variability (Coefficient of Variation) | 0.9 percentage | Standard Error 0.9 |
Secondary
Change in HbA1c
HbA1c will be measured at a central laboratory and change in Hba1c from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.
Time frame: 26 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in HbA1c | -0.7 percentage HbA1c | Standard Error 0.1 |
| Control | Change in HbA1c | -0.4 percentage HbA1c | Standard Error 0.1 |
Secondary
Change in Mean Glucose
Mean glucose (mg/dL) will be obtained by CGM and change in mean CGM glucose from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.
Time frame: 26 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Mean Glucose | -15.7 mg/dL | Standard Error 2.6 |
| Control | Change in Mean Glucose | -3.6 mg/dL | Standard Error 2.8 |
Secondary
Change in Weight
The change in kg of body weight from baseline to 26 weeks will be compared by randomization group using an ITT analysis.
Time frame: 26 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Change in Weight | -9.2 kg | Standard Error 0.7 |
| Control | Change in Weight | -0.4 kg | Standard Error 0.6 |
Secondary
Percent Time Spent in CGM-measured Glucose >180 mg/dL
Percent of time spent in glucose range \>180 mg/dL will be obtained by CGM and change in mean CGM glucose from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.
Time frame: 26 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Percent Time Spent in CGM-measured Glucose >180 mg/dL | -11.1 percentage | Standard Error 1.8 |
| Control | Percent Time Spent in CGM-measured Glucose >180 mg/dL | -2.7 percentage | Standard Error 1.9 |
Secondary
Percent Time Spent in CGM-measured Glucose >250mg/dL
Percent of time spent in glucose range \>250 mg/dL will be obtained by CGM and change in mean CGM glucose from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.
Time frame: 26 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Percent Time Spent in CGM-measured Glucose >250mg/dL | -5.1 percentage | Standard Error 1.1 |
| Control | Percent Time Spent in CGM-measured Glucose >250mg/dL | -0.5 percentage | Standard Error 1.2 |
Secondary
Percent Time Spent in CGM-measured Glucose <70mg/dL
Percent of time spent in glucose range \<70 mg/dL will be obtained by CGM and change in mean CGM glucose from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.
Time frame: 26 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Percent Time Spent in CGM-measured Glucose <70mg/dL | 0.1 percentage | Standard Error 0.2 |
| Control | Percent Time Spent in CGM-measured Glucose <70mg/dL | 0.4 percentage | Standard Error 0.2 |
Secondary
Percent Time Spent in CGM-measured Glucose Range of 70-140 mg/dL (Time in Tight Target Range; TTIR)
Percent of time spent in tight glucose range (70-140 mg/dL) will be obtained by CGM and change in percent time in range from baseline to 26 weeks will be compared by randomization group using intention to treat (ITT) analysis.
Time frame: 26 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Semaglutide | Percent Time Spent in CGM-measured Glucose Range of 70-140 mg/dL (Time in Tight Target Range; TTIR) | 9.8 percentage of time | Standard Error 1.7 |
| Control | Percent Time Spent in CGM-measured Glucose Range of 70-140 mg/dL (Time in Tight Target Range; TTIR) | 2.9 percentage of time | Standard Error 1.8 |
Secondary
Severe Hypoglycemia
SH events in number of patients per group
Time frame: 26 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Semaglutide | Severe Hypoglycemia | 2 Participants |
| Control | Severe Hypoglycemia | 2 Participants |
Other Pre-specified
Achievement of Primary Outcome and Key Secondary Outcomes by Types of AID Systems
Proportion of participants achieving primary outcome and key secondary glycemic outcomes by types of AID systems
Time frame: 26 weeks
Other Pre-specified
Achievement of Primary Outcomes by Baseline A1c (A1c <7.5% vs >7.5%)
Achievement of primary outcomes by baseline A1c (A1c \<7.5% vs \>7.5%)
Time frame: 26 weeks
Other Pre-specified
Achievement of Primary Outcomes by Baseline BMI (BMI <35 vs >35)
Achievement of primary outcomes by baseline BMI (BMI \<35 vs \>35)
Time frame: 26 weeks
Other Pre-specified
AID Setting Adjustment
Defined any adjustment in settings by provider or patient per person over the study period by two groups (number of adjustments (N) during trial) between two groups
Time frame: 26 weeks
Other Pre-specified
Change in Basal Insulin Per Day
Change in basal insulin per day (Total basal insulin including autobasal delivery, units per day and U/kg/day) between two groups
Time frame: 26 weeks
Other Pre-specified
Change in Brach D
Change in brachial arterial distensibility between two groups
Time frame: 26 weeks
Other Pre-specified
Change in Carbohydrate Intake Per Day (Grams/Day)
Change in Carbohydrate intake per day (grams/day) between two groups
Time frame: 26 weeks
Other Pre-specified
Change in Carotid Intima Media Thickness (cIMT)
Change in carotid intima media thickness (cIMT) between two groups
Time frame: 26 weeks
Other Pre-specified
Change in CGM Metrics by Daytime vs Nighttime
Change in CGM metrics (TIR, TITR, mean glucose, TBR, TAR \>180, SD, CV) by daytime (6 AM to \<11 PM) and nighttime (11 PM to \<6 AM) between two groups
Time frame: 26 weeks
Other Pre-specified
Change in Diastolic Blood Pressure (DBP)
change in DBP (mmHg) between two groups
Time frame: 26 weeks
Other Pre-specified
Change in eGFR
Change in eGFR using CKD-EPI between two groups
Time frame: 26 weeks
Other Pre-specified
Change in Femoral to Carotid Pulse Wave Velocity (m/s)
Change in femoral to carotid pulse wave velocity (m/s) between two groups
Time frame: 26 weeks
Other Pre-specified
Change in Fib-4 Score
Change in Fib-4 score between two groups
Time frame: 26 weeks
Other Pre-specified
Change in HDL-C
Change in HDL-C between two groups
Time frame: 26 weeks
Other Pre-specified
Change in HSI (Hepatic Steatosis Index)
Change in HSI (hepatic steatosis index) between two groups
Time frame: 26 weeks
Other Pre-specified
Change in LDL-C
Change in LDL-C between two groups
Time frame: 26 weeks
Other Pre-specified
Change in MRI Measured Pulse Wave Velocity and Longitudinal Strain
Change in MRI measured pulse wave velocity and longitudinal strain between two groups
Time frame: 26 weeks
Other Pre-specified
Change in Patient Reported Quality of Life
Patient reported quality of life will be measured using a validated instrument (ADDQOL) and the change in score from baseline to 26 weeks will be compared by randomization group using an ITT analysis.
Time frame: 26 weeks
Other Pre-specified
Change in Pulse Pressure
change in pulse pressure between two groups
Time frame: 26 weeks
Other Pre-specified
Change in Systolic Blood Pressure (SBP)
change in SBP (mmHg) between two groups
Time frame: 26 weeks
Other Pre-specified
Change in TC
Change in TC between two groups
Time frame: 26 weeks
Other Pre-specified
Change in TG
Change in TG between two groups
Time frame: 26 weeks
Other Pre-specified
Change in Total Boluses Per Day
Change in total boluses per day (frequency of boluses per day) between two groups
Time frame: 26 weeks
Other Pre-specified
Change in Total Bolus Insulin Per Day
Change in total bolus insulin per day (units per day and U/Kg/day) between two groups
Time frame: 26 weeks
Other Pre-specified
Change in Total Daily Dose of Insulin (TDD, Units Per Day and U/Kg/Day)
Change in TDD between two groups
Time frame: 26 weeks
Other Pre-specified
Change in Triglyceride/HDL Ratio
Change in triglyceride/HDL ratio between two groups
Time frame: 26 weeks
Other Pre-specified
Change in Urine Albumin to Creatinine Ratio (ACR)
Change in ACR between two groups
Time frame: 26 weeks
Other Pre-specified
HbA1c Improvement
HbA1c improvement from baseline to 26 weeks between two groups
Time frame: 26 weeks
Other Pre-specified
HbA1c Improvement of >0.4% From Baseline
proportion of participants with HbA1c improvement of \>0.4% from baseline between two groups
Time frame: 26 weeks
Other Pre-specified
Number of TBR <54 Events
Numbers of events of CGM glucose \<54mg/dL lasting for at least 15 minutes between two groups
Time frame: 26 weeks
Other Pre-specified
Number of TBR<70 Events
Numbers of events of CGM glucose \<70 mg/dL lasting for at least 15 minutes between two groups
Time frame: 26 weeks
Other Pre-specified
Proportion Achieving Weight Loss ≥10%
Proportion of participants achieving weight loss ≥10% from baseline between two groups
Time frame: 26 weeks
Other Pre-specified
Proportion Achieving Weight Loss ≥5%
Proportion of participants achieving weight loss ≥5% from baseline between two groups
Time frame: 26 weeks
Other Pre-specified
Proportion of Achieving BMI <25 kg/m2
Proportion of participants achieving BMI \<25 kg/m2 between two groups
Time frame: 26 weeks
Other Pre-specified
Proportion of Achieving BMI <30 kg/m2
Proportion of participants achieving BMI \<30 kg/m2 between two groups
Time frame: 26 weeks
Other Pre-specified
Proportion of Participants Achieving TIR >70%
Proportion of participants achieving TIR \>70% between two groups over 26 weeks
Time frame: 26 weeks
Other Pre-specified
Proportion of Participants Achieving TIR >80%
Proportion of participants achieving TIR \>80% between two groups
Time frame: 26 weeks
Other Pre-specified
Proportion of Participants Achieving TITR >50%
Proportion of participants achieving TITR (time in 70-140 mg/dL) \>50% between two groups
Time frame: 26 weeks
Other Pre-specified
Proportion of Participants Achieving TITR >60%
Proportion of participants achieving TITR (time in 70-140 mg/dL) \>60% between two groups
Time frame: 26 weeks
Other Pre-specified
Proportion of Participants With HbA1c <7%
proportion (N, %) of participants achieving HbA1c \<7% between two groups over 26 weeks
Time frame: 26 weeks
Other Pre-specified
Proportion of Participants With HbA1c <7.5%
proportion (N, %) of participants achieving HbA1c \<7.5% between two groups over 26 weeks
Time frame: 26 weeks
Other Pre-specified
Proportion With ACR <30 at 26 Weeks
Proportion of participants with ACR \<30 at 26 weeks between two groups
Time frame: 26 weeks
Other Pre-specified
Proportion With Change in ACR From >30 to <30
Proportion of participants with change in ACR from \>30 to \<30 between two groups
Time frame: 26 weeks
Other Pre-specified
Quality of Life (Diabetes Dependent QOL)
Change in QOL between two groups
Time frame: 26 weeks