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Mechanistic Insights to Weight Loss Maintenance Through SGLT2 Inhibitors

Phase 2
Withdrawn
Conditions
Obesity
Weight Loss
Interventions
Other: Control Arm
Other: Exercise capacity VO2 maximum determination
Other: Exercise Challenge
Registration Number
NCT05885074
Lead Sponsor
University of Alabama at Birmingham
Brief Summary

Obesity increases the risk of cardiometabolic diseases such as hypertension and diabetes. Weight loss interventions such as low-calorie diet and physical activity are effective for weight loss in the short term, but weight loss maintenance (WLM) with low-calorie diet and physical activity is challenging. Weight loss is associated with a reduction in the amount of calories needed to maintain the body at rest, called the resting energy expenditure (REE), which may be a probable mechanism for this lack of WLM. Most individuals are unable to adequately change their diet and increase their physical activity levels to overcome this decrease in REE which prevents WLM. Therefore, techniques that increase REE may promote WLM in these individuals. Pre-clinical studies for Empagliflozin - Sodium-glucose Cotransporter-2 (SGLT2) inhibitor have shown an increase in REE. Thus, in addition to reducing the cardiovascular risk, SGLT2 inhibitor may promote WLM by increasing REE. This study aims to promote WLM in obese individuals by increasing the REE using SGLT2 inhibitor therapy.

Detailed Description

Not available

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria
  • Age more than or equal to 18 years
  • Body mass index more than or equal to 30 kg/m2 who have lost ≥5% of body weight within the past 6 months without taking any pharmacotherapy for weight loss
Exclusion Criteria
  • Age less than 18 years at screening.
  • Untreated systolic BP <100 or >160 mmHg at baseline, or diastolic BP <80 or >100 mmHg at baseline
  • Women who are pregnant or breastfeeding or who can become pregnant and not practicing an acceptable method of birth control during the study (including abstinence)
  • Taking pharmacotherapy indicated for weight loss, such as GLP-1 agonists or with weight loss as an adverse event
  • History of Type I Diabetes
  • History of lung disease
  • Have any past or present illness of cardiovascular disease, including myocardial infarction, angina, cardiac arrhythmia, diabetes, stroke, TIA, or seizure
  • Current or past (<12 months) history of smoking
  • Estimated glomerular filtration rate (GFR) < 60 ml/min/1.73 m2 (CKD-EPI equation) urine albumin creatinine ratio ≥30 mg/g
  • Hepatic Transaminase (AST and ALT) levels >3x the upper limit of normal
  • Significant psychiatric illness
  • Anemia (men, Hct < 38%; women, Hct <36%)
  • Inability to exercise on a treadmill
  • Consumption of more than 2 alcoholic drinks daily
  • Any contraindications to empagliflozin

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Empagliflozin ArmEmpagliflozin ArmInvestigator will enroll 12 obese participants who have intentionally lost greater than or equal to 5% of body weight through a non-pharmacological structured weight loss program based on diet and exercise within the last 6 months. The participants will take empagliflozin 25mg/day orally for 12 months.
Empagliflozin ArmExercise ChallengeInvestigator will enroll 12 obese participants who have intentionally lost greater than or equal to 5% of body weight through a non-pharmacological structured weight loss program based on diet and exercise within the last 6 months. The participants will take empagliflozin 25mg/day orally for 12 months.
Empagliflozin ArmExercise capacity VO2 maximum determinationInvestigator will enroll 12 obese participants who have intentionally lost greater than or equal to 5% of body weight through a non-pharmacological structured weight loss program based on diet and exercise within the last 6 months. The participants will take empagliflozin 25mg/day orally for 12 months.
Placebo ArmControl ArmInvestigator will enroll 12 obese participants who have intentionally lost greater than or equal to 5% of body weight through a non-pharmacological structured weight loss program based on diet and exercise within the last 6 months. The participants will take a placebo pill orally once a day for 12 months.
Placebo ArmExercise ChallengeInvestigator will enroll 12 obese participants who have intentionally lost greater than or equal to 5% of body weight through a non-pharmacological structured weight loss program based on diet and exercise within the last 6 months. The participants will take a placebo pill orally once a day for 12 months.
Placebo ArmExercise capacity VO2 maximum determinationInvestigator will enroll 12 obese participants who have intentionally lost greater than or equal to 5% of body weight through a non-pharmacological structured weight loss program based on diet and exercise within the last 6 months. The participants will take a placebo pill orally once a day for 12 months.
Primary Outcome Measures
NameTimeMethod
Change in Resting Energy Expenditure12 months

Change in Resting Energy Expenditure between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention

Secondary Outcome Measures
NameTimeMethod
Change in glucagon-like peptide-1 (GLP-1)12 months

Change in glucagon-like peptide-1 (GLP-1) between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention

Change in TNF-α12 months

Change in TNF-α between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention

Change in Body Weight12 months

Change in Body Weight between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention

Change in HbA1C levels12 months

Change in HbA1C levels between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention

Change in CRP12 months

Change in CRP between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention

Change in ghrelin12 months

Change in ghrelin between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention

Change in Waist Circumference12 months

Change in Waist Circumference between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention

Change in ESR12 months

Change in ESR between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention

Change in peptide YY (PYY)12 months

Change in peptide YY (PYY) between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention

Change in glucose-dependent insulinotropic polypeptide (GIP)12 months

Change in glucose-dependent insulinotropic polypeptide (GIP) between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention

Change in Body Mass Index12 months

Change in Body Mass Index between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention

Change in lipid profile12 months

Change in Lipid profile between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention

Change in HOMA-IR12 months

Change in HOMA-IR between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention

Change in IL-612 months

Change in IL-6 between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention

Change in glucagon12 months

Change in glucagon between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention

Trial Locations

Locations (1)

University of Alabama at Birmingham

🇺🇸

Birmingham, Alabama, United States

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