Trial Outcomes & Findings for CARAT: Canagliflozin vs. Placebo for Post Bariatric Patients With Persistent Type 2 Diabetes (NCT NCT02912455)

NCT ID: NCT02912455

Last Updated: 2020-11-20

Results Overview

The change in hemoglobin A1c from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 16 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2020-11-20

Participant Flow

Participant milestones

Measure	Study Drug (Canagliflozin) Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 11). canagliflozin: encapsulated (gelatin capsule).	Placebo Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =5). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Overall Study STARTED	11	5
Overall Study COMPLETED	9	2
Overall Study NOT COMPLETED	2	3

Reasons for withdrawal

Measure	Study Drug (Canagliflozin) Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 11). canagliflozin: encapsulated (gelatin capsule).	Placebo Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =5). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Overall Study Withdrawal by Subject	0	1
Overall Study Lack of Efficacy	0	1
Overall Study Lost to Follow-up	2	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily. canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Drug: Placebo (for canagliflozin) encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.	Total n=16 Participants Total of all reporting groups
Age, Continuous	58 years n=11 Participants	44.0 years n=5 Participants	54.0 years n=16 Participants
Sex: Female, Male Female	7 Participants n=11 Participants	4 Participants n=5 Participants	11 Participants n=16 Participants
Sex: Female, Male Male	4 Participants n=11 Participants	1 Participants n=5 Participants	5 Participants n=16 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment United States	11 participants n=11 Participants	5 participants n=5 Participants	16 participants n=16 Participants
BMI	39.6 kg/m^2 n=11 Participants	37.9 kg/m^2 n=5 Participants	39.2 kg/m^2 n=16 Participants
Height (m)	1.7 meters n=11 Participants	1.7 meters n=5 Participants	1.7 meters n=16 Participants
Weight (kg)	108.6 kg n=11 Participants	117.5 kg n=5 Participants	108.9 kg n=16 Participants
Hemoglobin A1c (%)	7.2 percent n=11 Participants	8.2 percent n=5 Participants	7.4 percent n=16 Participants
Fasting glucose (mg/dL)	163.0 mg/dL n=11 Participants	164.0 mg/dL n=5 Participants	163.5 mg/dL n=16 Participants
Diastolic blood pressure (mm/Hg)	73.0 mmHg n=11 Participants	77.0 mmHg n=5 Participants	76.5 mmHg n=16 Participants
Systolic blood pressure (mm/Hg)	137.0 mmHg n=11 Participants	133.0 mmHg n=5 Participants	134.5 mmHg n=16 Participants
Uric acid (mg/dL)	4.9 mg/dL n=11 Participants	3.9 mg/dL n=5 Participants	4.3 mg/dL n=16 Participants
Total cholesterol (mg/dL)	160.0 mg/dL n=11 Participants	167.0 mg/dL n=5 Participants	162.0 mg/dL n=16 Participants
Triglycerides (mg/dL)	130.0 mg/dL n=11 Participants	107.0 mg/dL n=5 Participants	109.5 mg/dL n=16 Participants
LDL (mg/dL)	87.0 mg/dL n=11 Participants	108.0 mg/dL n=5 Participants	92.0 mg/dL n=16 Participants
HDL (mg/dL)	47.0 mg/dL n=11 Participants	51.0 mg/dL n=5 Participants	49.0 mg/dL n=16 Participants
Body fat %	49.3 percentage of body fat n=11 Participants	44.1 percentage of body fat n=5 Participants	48.6 percentage of body fat n=16 Participants
Lean mass %	50.7 percentage of lean mass n=11 Participants	55.9 percentage of lean mass n=5 Participants	51.5 percentage of lean mass n=16 Participants
Truncal fat	53.5 percentage of truncal fat n=11 Participants	47.8 percentage of truncal fat n=5 Participants	50.9 percentage of truncal fat n=16 Participants
Android fat	55.6 percentage of android fat n=11 Participants	51.3 percentage of android fat n=5 Participants	53.9 percentage of android fat n=16 Participants
Gynoid fat	48.1 percentage of gynoid fat n=11 Participants	47.3 percentage of gynoid fat n=5 Participants	47.7 percentage of gynoid fat n=16 Participants
Spine BMD	1.2 g/cm^2 n=11 Participants	1.3 g/cm^2 n=5 Participants	1.2 g/cm^2 n=16 Participants
Leg BMD	1.2 g/cm^2 n=11 Participants	1.2 g/cm^2 n=5 Participants	1.2 g/cm^2 n=16 Participants
HMW adiponectin	2.9 ug/mL n=11 Participants	3.3 ug/mL n=5 Participants	3.1 ug/mL n=16 Participants
Adiponectin	4.2 ug/mL n=11 Participants	5 ug/mL n=5 Participants	4.6 ug/mL n=16 Participants
Leptin	28 ng/mL n=11 Participants	29 ng/mL n=5 Participants	28.5 ng/mL n=16 Participants
CRP	4.1 mg/L n=11 Participants	0.45 mg/L n=5 Participants	3.7 mg/L n=16 Participants

PRIMARY outcome

Timeframe: 6 months

The change in hemoglobin A1c from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery

Outcome measures

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Change at Six Months Versus Baseline in Hemoglobin A1c Value (%)	-0.31 percentage Interval -0.72 to 0.1	0.11 percentage Interval -0.71 to 0.93

SECONDARY outcome

Timeframe: 6 months

The change in fasting glucose from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery.

Outcome measures

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Change in Fasting Glucose From Randomization	-32.90 mg/dL Interval -56.02 to -9.79	-44.61 mg/dL Interval -102.39 to 13.17

SECONDARY outcome

Timeframe: 6 months

The change in body weight from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery.

Outcome measures

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Change in Body Weight at Six Months Compared to Baseline	-3.77 kilograms Interval -6.33 to -1.22	6.33 kilograms Interval -1.5 to 14.16

SECONDARY outcome

Timeframe: 6 months

The change in total cholesterol from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery

Outcome measures

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Change in Total Cholesterol	-0.87 mg/dL Interval -26.59 to 24.85	3.69 mg/dL Interval -37.53 to 44.92

SECONDARY outcome

Timeframe: 6 months

The change in diastolic blood pressure from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery

Outcome measures

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Change in Diastolic Blood Pressure at Six Months Compared to Baseline	-1.18 mmHg Interval -6.62 to 4.26	2.95 mmHg Interval -13.69 to 19.6

SECONDARY outcome

Timeframe: 6 months

The change in adiponectin levels from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery.

Outcome measures

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Change in Adiponectin Levels at 6 Months Compared to Randomization	0.7 ug/mL Interval -2.2 to 5.7	-3.4 ug/mL Interval -9.3 to 2.5

SECONDARY outcome

Timeframe: 6 months

Change in leptin levels at 6 months compared to baseline The change in leptin levels from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery.

Outcome measures

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Change in Leptin Levels at 6 Months Compared to Baseline	-8.1 ng/mL Interval -35.1 to 18.9	-11 ng/mL Interval -93.1 to 71.1

SECONDARY outcome

Timeframe: 6 months

The change in C-reactive protein levels from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery.

Outcome measures

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Change in CRP Levels at 6 Months Compared to Baseline	-5.35 mg/L Interval -13.81 to 3.12	3.34 mg/L Interval -0.76 to 7.44

SECONDARY outcome

Timeframe: 6 months

The number of participants who reported symptomatic hypoglycemia episodes from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery.

Outcome measures

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Number of Participants Who Reported Hypoglycemia From Each Group (at a Frequency of 1 Episode)	2 participants	0 participants

SECONDARY outcome

Timeframe: 6 months

The change in body fat from randomization following the 6 month administration of canagliflozin vs. placebo in patients with type 2 diabetes post-bariatric surgery.

Outcome measures

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Change in Percent Body Fat as Measured by DEXA Scan at 6 Months Compared to Randomization	-1.82 percent change Interval -3.83 to 0.2	2.65 percent change Interval -1.21 to 6.51

SECONDARY outcome

Timeframe: 6 months

The Change in Systolic Blood Pressure From Randomization Following the 6 Month Administration of Canagliflozin vs. Placebo in Patients With Type 2 Diabetes Post-bariatric Surgery

Outcome measures

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Change in Systolic Blood Pressure at 6 Months Compared to Baseline	4.62 mmHg Interval -7.1 to 16.34	12.63 mmHg Interval -5.02 to 30.28

SECONDARY outcome

Timeframe: 6 months

Change in percentage of lean body mass as measured by DEXA scan at 6 months compared to randomization

Outcome measures

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Change in Percentage of Lean Mass	1.82 percent change Interval -0.2 to 3.83	-2.65 percent change Interval -6.51 to 1.21

SECONDARY outcome

Timeframe: 6 months

Change in percentage of truncal fat as measured by DEXA scan at 6 months compared to randomization

Outcome measures

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Change in Percentage of Truncal Fat	-2.67 percent change Interval -5.19 to -0.16	2.74 percent change Interval -0.14 to 5.63

SECONDARY outcome

Timeframe: 6 months

Change in percentage of android fat as measured by DEXA scan at 6 months compared to randomization

Outcome measures

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Change in Percentage of Android Fat	-3.00 percent change Interval -5.67 to -0.32	3.33 percent change Interval 0.23 to 6.43

SECONDARY outcome

Timeframe: 6 months

Change in percentage of gynoid fat as measured by DEXA scan at 6 months compared to randomization

Outcome measures

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Change in Percentage of Gynoid Fat	-1.69 percent change Interval -3.65 to 0.28	2.17 percent change Interval -2.26 to 6.59

SECONDARY outcome

Timeframe: 6 months

Change in spine bone marrow density as measured by DEXA scan at 6 months compared to randomization

Outcome measures

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Change in Spine Bone Mineral Density	-0.02 grams per square centimeter Interval -0.07 to 0.03	0.14 grams per square centimeter Interval -0.11 to 0.4

SECONDARY outcome

Timeframe: 6 months

Change in leg bone marrow density as measured by DEXA scan at 6 months compared to randomization

Outcome measures

Measure	Study Drug (Canagliflozin) n=11 Participants Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 Participants Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Change in Leg Bone Mineral Density	0.01 grams per square centimeter Interval -0.03 to 0.05	-0.04 grams per square centimeter Interval -0.37 to 0.28

Adverse Events

Study Drug (Canagliflozin)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Study Drug (Canagliflozin) n=11 participants at risk Subjects randomized to study drug will be assigned a six month course starting on canagliflozin 100 mg for two weeks titrated up to 300 mg daily (n= 24). canagliflozin: encapsulated (gelatin capsule).	Placebo n=5 participants at risk Subjects randomized to placebo will be assigned a six month course of one placebo pill daily (n =12). Placebo (for canagliflozin): encapsulated (gelatin capsule). The placebo capsule filler is called micro-crystalline cellulose.
Metabolism and nutrition disorders Hypoglycemia	18.2% 2/11 • Number of events 2 • Adverse events were collected over a period of 6 months.	0.00% 0/5 • Adverse events were collected over a period of 6 months.
Metabolism and nutrition disorders Hyperglycemia	45.5% 5/11 • Number of events 8 • Adverse events were collected over a period of 6 months.	20.0% 1/5 • Number of events 2 • Adverse events were collected over a period of 6 months.
Metabolism and nutrition disorders Dehydration	18.2% 2/11 • Number of events 3 • Adverse events were collected over a period of 6 months.	0.00% 0/5 • Adverse events were collected over a period of 6 months.
Metabolism and nutrition disorders Increased thirst	45.5% 5/11 • Number of events 6 • Adverse events were collected over a period of 6 months.	40.0% 2/5 • Number of events 2 • Adverse events were collected over a period of 6 months.
Metabolism and nutrition disorders Increased urination	45.5% 5/11 • Number of events 6 • Adverse events were collected over a period of 6 months.	40.0% 2/5 • Number of events 2 • Adverse events were collected over a period of 6 months.
Renal and urinary disorders Urinary tract infection	9.1% 1/11 • Number of events 1 • Adverse events were collected over a period of 6 months.	20.0% 1/5 • Number of events 1 • Adverse events were collected over a period of 6 months.
Renal and urinary disorders Genital yeast infection	18.2% 2/11 • Number of events 2 • Adverse events were collected over a period of 6 months.	0.00% 0/5 • Adverse events were collected over a period of 6 months.
Gastrointestinal disorders Constipation	9.1% 1/11 • Number of events 1 • Adverse events were collected over a period of 6 months.	0.00% 0/5 • Adverse events were collected over a period of 6 months.
Nervous system disorders Lightheadedness	18.2% 2/11 • Number of events 2 • Adverse events were collected over a period of 6 months.	0.00% 0/5 • Adverse events were collected over a period of 6 months.
Gastrointestinal disorders Nausea	9.1% 1/11 • Number of events 1 • Adverse events were collected over a period of 6 months.	0.00% 0/5 • Adverse events were collected over a period of 6 months.
Investigations Increased hunger	0.00% 0/11 • Adverse events were collected over a period of 6 months.	20.0% 1/5 • Number of events 1 • Adverse events were collected over a period of 6 months.
Nervous system disorders Syncope	0.00% 0/11 • Adverse events were collected over a period of 6 months.	20.0% 1/5 • Number of events 1 • Adverse events were collected over a period of 6 months.

Additional Information

Dr. Sangeeta Kashyap

Cleveland Clinic

Phone: (216) 445-2679

Email: kashyas@ccf.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place