Trial Outcomes & Findings for Raising Insulin Sensitivity in Post Menopause (NCT NCT02274571)

NCT ID: NCT02274571

Last Updated: 2025-06-04

Results Overview

• Recruitment status: COMPLETED
• Study phase: EARLY_PHASE1
• Target enrollment: 8 participants
• Primary outcome timeframe: 8 weeks
• Results posted on: 2025-06-04

Participant Flow

269 applied to participate. 82 completed a web base screening. 18 screened in the clinic. 10 were ineligible and 8 enrolled and were randomized and completed the study.

the 10 ineligible were 5 BMI out of range. 2 > 5 year post menopause. 1 because of medication. 1 for medical condition and 1 failed to return to clinic.

Participant milestones

Measure	TSEC (Duavee™, Combination of CE and BZA), Then Placebo Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period, then after an 8-week washout, participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period).	Placebo, Then TSEC (Duavee™, Combination of CE and BZA) Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period), then after an 8-week washout, participants received TSEC 0.45/20 mg per day each for an 8-week treatment period.
Overall Study STARTED	4	4
Overall Study COMPLETED	4	4
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Raising Insulin Sensitivity in Post Menopause

Baseline characteristics by cohort

Measure	Enrolled Female Participants n=8 Participants This study involves a screening process to see if you are eligible to participate followed by two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Age, Customized Age 50-60 years	8 years n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	8 Participants n=5 Participants

PRIMARY outcome

Timeframe: 8 weeks

Outcome measures

Measure	Placebo n=8 Participants Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period. Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).	TSEC (Duavee™, Combination of CE and BZA) n=8 Participants Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period) Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Effect of CE/BZA (TSEC) on Body Composition Weight	91.3 Kilograms Standard Deviation 6.8	90.6 Kilograms Standard Deviation 7.2
Effect of CE/BZA (TSEC) on Body Composition Fat Mass	45.5 Kilograms Standard Deviation 4.6	45.7 Kilograms Standard Deviation 4.0
Effect of CE/BZA (TSEC) on Body Composition Fat-free Mass	46.0 Kilograms Standard Deviation 3.5	45.5 Kilograms Standard Deviation 4.0

PRIMARY outcome

Timeframe: 8 weeks

Outcome measures

Measure	Placebo n=8 Participants Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period. Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).	TSEC (Duavee™, Combination of CE and BZA) n=8 Participants Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period) Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Effect of CE/BZA (TSEC) on Ectopic Fat - 1H-MRS, Proton Magnetic Resonance Spectroscopy Soleus intramyocellular lipid (IMCL)	0.29 Percent Standard Deviation 0.27	0.36 Percent Standard Deviation 0.47
Effect of CE/BZA (TSEC) on Ectopic Fat - 1H-MRS, Proton Magnetic Resonance Spectroscopy Soleus extramyocellular lipid (EMCL)	0.32 Percent Standard Deviation 0.28	0.43 Percent Standard Deviation 0.45
Effect of CE/BZA (TSEC) on Ectopic Fat - 1H-MRS, Proton Magnetic Resonance Spectroscopy Tibialis anterior intramyocellular lipid (IMCL)	0.33 Percent Standard Deviation 0.23	0.69 Percent Standard Deviation 0.50
Effect of CE/BZA (TSEC) on Ectopic Fat - 1H-MRS, Proton Magnetic Resonance Spectroscopy Intrahepatic Lipid (IHL)	9.00 Percent Standard Deviation 13.9	8.06 Percent Standard Deviation 9.14
Effect of CE/BZA (TSEC) on Ectopic Fat - 1H-MRS, Proton Magnetic Resonance Spectroscopy Tibialis anterior extramyocellular lipid (EMCL)	1.87 Percent Standard Deviation 1.60	4.13 Percent Standard Deviation 6.06

PRIMARY outcome

Timeframe: 8 weeks

Outcome measures

Measure	Placebo n=8 Participants Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period. Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).	TSEC (Duavee™, Combination of CE and BZA) n=8 Participants Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period) Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Effect of CE/BZA (TSEC) on Abdominal Fat Cell Size (by Biopsy) Small Fat Cells	66.4 Percent Standard Deviation 8.7	66.0 Percent Standard Deviation 5.5
Effect of CE/BZA (TSEC) on Abdominal Fat Cell Size (by Biopsy) Large Fat Cells	33.6 Percent Standard Deviation 8.7	34.0 Percent Standard Deviation 5.5

PRIMARY outcome

Timeframe: 8 weeks

Outcome measures

Measure	Placebo n=8 Participants Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period. Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).	TSEC (Duavee™, Combination of CE and BZA) n=8 Participants Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period) Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Effect of CE/BZA (TSEC) on Body Mass Index	36.6 kilograms per meter squared Standard Deviation 2.7	36.4 kilograms per meter squared Standard Deviation 2.9

PRIMARY outcome

Timeframe: 8 weeks

Outcome measures

Measure	Placebo n=8 Participants Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period. Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).	TSEC (Duavee™, Combination of CE and BZA) n=8 Participants Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period) Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Effect of CE/BZA (TSEC) on Percent Body Fat	50.9 percentage of total body weight Standard Deviation 2.5	51.4 percentage of total body weight Standard Deviation 1.9

PRIMARY outcome

Timeframe: 8 weeks

Outcome measures

Measure	Placebo n=8 Participants Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period. Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).	TSEC (Duavee™, Combination of CE and BZA) n=8 Participants Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period) Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Effect of CE/BZA (TSEC) on Fat Cell Ratio (Small/Large)	2.19 ratio Standard Deviation 1.00	2.00 ratio Standard Deviation 0.45

PRIMARY outcome

Timeframe: 8 weeks

Outcome measures

Measure	Placebo n=8 Participants Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period. Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).	TSEC (Duavee™, Combination of CE and BZA) n=8 Participants Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period) Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Effect of CE/BZA (TSEC) on Mean Fat Cell Size	1.35 um^3 (x10^6) Standard Deviation 0.4	1.6 um^3 (x10^6) Standard Deviation 0.4

SECONDARY outcome

Timeframe: 8 weeks

Outcome measures

Measure	Placebo n=8 Participants Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period. Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).	TSEC (Duavee™, Combination of CE and BZA) n=8 Participants Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period) Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Effect of CE/BZA (TSEC) on Fasting Labs LDL-cholesterol	100 Milligrams/deciliter Standard Deviation 24	99 Milligrams/deciliter Standard Deviation 20
Effect of CE/BZA (TSEC) on Fasting Labs Glucose	105 Milligrams/deciliter Standard Deviation 4	102 Milligrams/deciliter Standard Deviation 4
Effect of CE/BZA (TSEC) on Fasting Labs Total cholesterol	179 Milligrams/deciliter Standard Deviation 34	187 Milligrams/deciliter Standard Deviation 32
Effect of CE/BZA (TSEC) on Fasting Labs Triglycerides	138 Milligrams/deciliter Standard Deviation 75	156 Milligrams/deciliter Standard Deviation 73
Effect of CE/BZA (TSEC) on Fasting Labs HDL-cholesterol	51 Milligrams/deciliter Standard Deviation 11	57 Milligrams/deciliter Standard Deviation 14

SECONDARY outcome

Timeframe: 8 weeks

Low-Dose Insulin [20 mIU/min/m2 ], High-Dose Insulin [120 mIU/min/m2 ]

Outcome measures

Measure	Placebo n=8 Participants Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period. Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).	TSEC (Duavee™, Combination of CE and BZA) n=8 Participants Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period) Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Effect of CE/BZA on Insulin Sensitivity (by Hyperinsulinemic-Euglycemic Clamp) Basal SGO	2.83 mg/min [FFM+17.7] Standard Deviation 0.41	2.68 mg/min [FFM+17.7] Standard Deviation 0.32
Effect of CE/BZA on Insulin Sensitivity (by Hyperinsulinemic-Euglycemic Clamp) GDR at Low-Dose Insulin	2.48 mg/min [FFM+17.7] Standard Deviation 0.91	2.55 mg/min [FFM+17.7] Standard Deviation 1.04
Effect of CE/BZA on Insulin Sensitivity (by Hyperinsulinemic-Euglycemic Clamp) GDR at High-Dose Insulin	11.99 mg/min [FFM+17.7] Standard Deviation 4.49	11.68 mg/min [FFM+17.7] Standard Deviation 4.23

SECONDARY outcome

Timeframe: 8 weeks

Population: No data reported for FFA for High-Dose Insulin

Low-Dose Insulin [20 mIU/min/m2 ] High-Dose Insulin [120 mIU/min/m2 ]

Outcome measures

Measure	Placebo n=8 Participants Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period. Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).	TSEC (Duavee™, Combination of CE and BZA) n=8 Participants Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period) Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Effect of CE/BZA (TSEC) on Insulin Sensitivity (by Hyperinsulinemic-Euglycemic Clamp) on FFA Free Fatty Acids (FFA) at Low-Dose Insulin	0.13 mmol/L Standard Deviation 0.05	0.13 mmol/L Standard Deviation 0.05
Effect of CE/BZA (TSEC) on Insulin Sensitivity (by Hyperinsulinemic-Euglycemic Clamp) on FFA Free Fatty Acids (FFA) at High-Dose Insulin	0 mmol/L Standard Deviation 0	0 mmol/L Standard Deviation 0

SECONDARY outcome

Timeframe: 8 weeks

Outcome measures

Measure	Placebo n=8 Participants Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period. Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).	TSEC (Duavee™, Combination of CE and BZA) n=8 Participants Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period) Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Effect of CE/BZA (TSEC) on Resting Metabolic Rate & Substrate Oxidation (by Indirect Calorimetry) Resting Metabolic Rate (RMR) on Low-Dose Insulin	1379 kcal/day Standard Deviation 94	1378 kcal/day Standard Deviation 137
Effect of CE/BZA (TSEC) on Resting Metabolic Rate & Substrate Oxidation (by Indirect Calorimetry) Resting Metabolic Rate (RMR) on High-Dose Insulin	1516 kcal/day Standard Deviation 113	1576 kcal/day Standard Deviation 83
Effect of CE/BZA (TSEC) on Resting Metabolic Rate & Substrate Oxidation (by Indirect Calorimetry) Resting Metabolic Rate (RMR) on Basal	1410 kcal/day Standard Deviation 126	1471 kcal/day Standard Deviation 161

SECONDARY outcome

Timeframe: 8 weeks

Low-Dose Insulin [20 mIU/min/m2 ], High-Dose Insulin [120 mIU/min/m2 ]

Outcome measures

Measure	Placebo n=8 Participants Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period. Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).	TSEC (Duavee™, Combination of CE and BZA) n=8 Participants Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period) Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Effect of CE/BZA (TSEC) on Resting Metabolic Rate & Substrate Oxidation (by Indirect Calorimetry) Carbohydrate Oxidation at Basal	1.2 mg/min/[FFM+17.7] Standard Deviation 0.1	1.0 mg/min/[FFM+17.7] Standard Deviation 0.1
Effect of CE/BZA (TSEC) on Resting Metabolic Rate & Substrate Oxidation (by Indirect Calorimetry) Carbohydrate Storage at Basal	1.6 mg/min/[FFM+17.7] Standard Deviation 0.3	1.6 mg/min/[FFM+17.7] Standard Deviation 0.3
Effect of CE/BZA (TSEC) on Resting Metabolic Rate & Substrate Oxidation (by Indirect Calorimetry) Carbohydrate Oxidation at Low-Dose	1.6 mg/min/[FFM+17.7] Standard Deviation 0.1	1.3 mg/min/[FFM+17.7] Standard Deviation 0.1
Effect of CE/BZA (TSEC) on Resting Metabolic Rate & Substrate Oxidation (by Indirect Calorimetry) Carbohydrate Storage at Low-dose	0.9 mg/min/[FFM+17.7] Standard Deviation 0.3	1.2 mg/min/[FFM+17.7] Standard Deviation 0.3
Effect of CE/BZA (TSEC) on Resting Metabolic Rate & Substrate Oxidation (by Indirect Calorimetry) Carbohydrate Oxidation at High-Dose	2.7 mg/min/[FFM+17.7] Standard Deviation 0.3	2.7 mg/min/[FFM+17.7] Standard Deviation 0.3
Effect of CE/BZA (TSEC) on Resting Metabolic Rate & Substrate Oxidation (by Indirect Calorimetry) Carbohydrate Storage at High-Dose	9.3 mg/min/[FFM+17.7] Standard Deviation 1.4	9.0 mg/min/[FFM+17.7] Standard Deviation 1.4

SECONDARY outcome

Timeframe: 8 weeks

Low-Dose Insulin [20 mIU/min/m2 ], High-Dose Insulin [120 mIU/min/m2 ]

Outcome measures

Measure	Placebo n=8 Participants Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period. Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).	TSEC (Duavee™, Combination of CE and BZA) n=8 Participants Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period) Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Effect of CE/BZA (TSEC) on Resting Metabolic Rate & Substrate Oxidation (by Indirect Calorimetry) Respiratory Quotient (RQ) at Basal	0.81 unitless Standard Deviation 0.03	0.80 unitless Standard Deviation 0.03
Effect of CE/BZA (TSEC) on Resting Metabolic Rate & Substrate Oxidation (by Indirect Calorimetry) Respiratory Quotient (RQ) at Low-Dose	0.85 unitless Standard Deviation 0.04	0.83 unitless Standard Deviation 0.03
Effect of CE/BZA (TSEC) on Resting Metabolic Rate & Substrate Oxidation (by Indirect Calorimetry) Respiratory Quotient (RQ) at Hight-Dose	0.92 unitless Standard Deviation 0.05	0.91 unitless Standard Deviation 0.06

SECONDARY outcome

Timeframe: 8 weeks

Outcome measures

Measure	Placebo n=8 Participants Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period. Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).	TSEC (Duavee™, Combination of CE and BZA) n=8 Participants Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period) Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Effect of CE/BZA (TSEC) on Fasting Insulin	16.6 uU/mL Standard Deviation 2.8	15.7 uU/mL Standard Deviation 2.8

SECONDARY outcome

Timeframe: 8 weeks

Outcome measures

Measure	Placebo n=8 Participants Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period. Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).	TSEC (Duavee™, Combination of CE and BZA) n=8 Participants Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period) Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Effect of CE/BZA (TSEC) on Fasting Free Fatty Acids	0.72 mmol/L Standard Deviation 0.06	0.78 mmol/L Standard Deviation 0.06

SECONDARY outcome

Timeframe: 8 weeks

Low-Dose Insulin [ 20 mIU/min/m2 ]

Outcome measures

Measure	Placebo n=8 Participants Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period. Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).	TSEC (Duavee™, Combination of CE and BZA) n=8 Participants Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period) Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Effect of CE/BZA on Insulin Sensitivity (by Hyperinsulinemic-Euglycemic Clamp) on Glucose Low-Dose Glucose	90 mg/dL Standard Deviation 1	88 mg/dL Standard Deviation 1
Effect of CE/BZA on Insulin Sensitivity (by Hyperinsulinemic-Euglycemic Clamp) on Glucose High-Dose Glucose	97 mg/dL Standard Deviation 3	95 mg/dL Standard Deviation 3

SECONDARY outcome

Timeframe: 8 weeks

Low-Dose Insulin [20 mIU/min/m2 ] High-Dose Insulin [120 mIU/min/m2 ]

Outcome measures

Measure	Placebo n=8 Participants Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period. Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).	TSEC (Duavee™, Combination of CE and BZA) n=8 Participants Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period) Two 8-week treatment periods separated by an 8-week washout period. The two 8-week treatments will be with: 8 weeks of treatment with TSEC (Duavee™, combination of CE and BZA) 8 weeks of treatment with a "dummy pill" (Placebo) The order of these 2 8-week treatment periods will be decided by chance (coin flip).
Effect of CE/BZA (TSEC) on Insulin Sensitivity (by Hyperinsulinemic-Euglycemic Clamp) on Insulin Insulin at Low-Dose Insulin	37.8 uU/mL Standard Deviation 2.4	34.8 uU/mL Standard Deviation 2.4
Effect of CE/BZA (TSEC) on Insulin Sensitivity (by Hyperinsulinemic-Euglycemic Clamp) on Insulin Insulin at High-Dose Insulin	250.8 uU/mL Standard Deviation 19.3	259.8 uU/mL Standard Deviation 19.3

Adverse Events

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

TSEC (Duavee™, Combination of CE and BZA)

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Placebo n=8 participants at risk Participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period), then after an 8-week washout, participants received TSEC 0.45/20 mg per day each for an 8-week treatment period	TSEC (Duavee™, Combination of CE and BZA) n=8 participants at risk Participants received TSEC 0.45/20 mg per day each for an 8-week treatment period, then after an 8-week washout, participants received Placebo tablet (matching TSEC 0.45/20 mg per day each for an 8-week treatment period)
Psychiatric disorders Neuropsychiatric	12.5% 1/8 • Number of events 1 • 24 weeks For reporting AE and SAE, all subject population was used.	12.5% 1/8 • Number of events 2 • 24 weeks For reporting AE and SAE, all subject population was used.
Respiratory, thoracic and mediastinal disorders Respiratory	12.5% 1/8 • Number of events 1 • 24 weeks For reporting AE and SAE, all subject population was used.	25.0% 2/8 • Number of events 4 • 24 weeks For reporting AE and SAE, all subject population was used.
Skin and subcutaneous tissue disorders Hematologic/oncologic	12.5% 1/8 • Number of events 1 • 24 weeks For reporting AE and SAE, all subject population was used.	0.00% 0/8 • 24 weeks For reporting AE and SAE, all subject population was used.
Musculoskeletal and connective tissue disorders Musculoskeletal	12.5% 1/8 • Number of events 1 • 24 weeks For reporting AE and SAE, all subject population was used.	50.0% 4/8 • Number of events 4 • 24 weeks For reporting AE and SAE, all subject population was used.
Gastrointestinal disorders Gastrointestinal	0.00% 0/8 • 24 weeks For reporting AE and SAE, all subject population was used.	12.5% 1/8 • Number of events 1 • 24 weeks For reporting AE and SAE, all subject population was used.
Renal and urinary disorders Genitourinary	25.0% 2/8 • Number of events 2 • 24 weeks For reporting AE and SAE, all subject population was used.	0.00% 0/8 • 24 weeks For reporting AE and SAE, all subject population was used.
Nervous system disorders Neurological	0.00% 0/8 • 24 weeks For reporting AE and SAE, all subject population was used.	12.5% 1/8 • Number of events 1 • 24 weeks For reporting AE and SAE, all subject population was used.
General disorders Oral Complaints	0.00% 0/8 • 24 weeks For reporting AE and SAE, all subject population was used.	12.5% 1/8 • Number of events 1 • 24 weeks For reporting AE and SAE, all subject population was used.
General disorders Nonspecific	12.5% 1/8 • Number of events 1 • 24 weeks For reporting AE and SAE, all subject population was used.	0.00% 0/8 • 24 weeks For reporting AE and SAE, all subject population was used.
General disorders Special Senses	0.00% 0/8 • 24 weeks For reporting AE and SAE, all subject population was used.	12.5% 1/8 • Number of events 2 • 24 weeks For reporting AE and SAE, all subject population was used.

Additional Information

Dr. Eric Ravussin

Pennington Biomedical Research Center

Phone: 2252844345

Email: eric.ravussin@pbrc.edu

Results disclosure agreements

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