Mechanistic Insights to Weight Loss Maintenance Through SGLT2 Inhibitors

NCT05885074 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: 300011125
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity; Weight Loss

Outcome Measures

Primary Outcomes (1)

• Change in Resting Energy Expenditure

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

  12 months

Secondary Outcomes (15)

• Change in Body Weight

  12 months

• Change in Body Mass Index

  12 months

• Change in Waist Circumference

  12 months

• Change in HbA1C levels

  12 months

• Change in lipid profile

  12 months

Study Arms (2)

Empagliflozin Arm

EXPERIMENTAL

Investigator 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.

Drug: Empagliflozin Arm; Other: Exercise capacity VO2 maximum determination; Other: Exercise Challenge

Placebo Arm

PLACEBO COMPARATOR

Investigator 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.

Other: Control Arm; Other: Exercise capacity VO2 maximum determination; Other: Exercise Challenge

Interventions

Empagliflozin Arm DRUG

The subject will be randomized, in a double-blind manner to Empagliflozin 25mg once daily for a period of 12 months

Empagliflozin Arm

Control Arm OTHER

The subject will be randomized, in a double-blind manner to receive placebo once daily for a period of 12 months

Placebo Arm

Exercise capacity VO2 maximum determination OTHER

Each participant's maximal oxygen capacity will be determined using a modified Bruce treadmill protocol and will also undergo a DEXA scan to determine the body mass.

Empagliflozin Arm; Placebo Arm

Exercise Challenge OTHER

Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill and will also undergo a resting energy expenditure test.

Empagliflozin Arm; Placebo Arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Obesity; Weight Loss

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Body Weight Changes

Study Officials

• Pankaj Arora, MD, FAHA

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 11, 2023
• First Posted: June 1, 2023
• Study Start: January 30, 2025
• Primary Completion: January 30, 2026
• Study Completion (Estimated): June 30, 2027
• Last Updated: August 7, 2024

Record last verified: 2024-08

Locations

US (1)