Mechanistic Insights to Weight Loss Maintenance Through SGLT2 Inhibitors

Obesity Clinical Trial

Official title:

Mechanistic Insights to Weight Loss Maintenance Through SGLT2 Inhibitors

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05885074
• Other study ID #: 300011125
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: January 30, 2025
• Est. completion date: June 30, 2027

Study information

• Verified date: January 2024
• Source: University of Alabama at Birmingham
• Contact: Nehal Vekariya, MS
• Phone: 2059347173
• Email: nvekariya[@]uabmc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 24
• Est. completion date: June 30, 2027
• Est. primary completion date: January 30, 2026
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Body Weight
• Obesity
• Weight Loss

Intervention

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

Other:
• Control Arm
The subject will be randomized, in a double-blind manner to receive placebo once daily for a period of 12 months
• Exercise capacity VO2 maximum determination
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.
• Exercise Challenge
Each participant will walk at 70 % of his/her VO2max for 20 minutes on treadmill and will also undergo a resting energy expenditure test.

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama

Sponsors (1)

Lead Sponsor	Collaborator
University of Alabama at Birmingham

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Change in Body Weight	Change in Body Weight between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention	12 months
Secondary	Change in Body Mass Index	Change in Body Mass Index between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention	12 months
Secondary	Change in Waist Circumference	Change in Waist Circumference between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention	12 months
Secondary	Change in HbA1C levels	Change in HbA1C levels between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention	12 months
Secondary	Change in lipid profile	Change in Lipid profile between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention	12 months
Secondary	Change in HOMA-IR	Change in HOMA-IR between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention	12 months
Secondary	Change in ESR	Change in ESR between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention	12 months
Secondary	Change in CRP	Change in CRP between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention	12 months
Secondary	Change in IL-6	Change in IL-6 between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention	12 months
Secondary	Change in TNF-a	Change in TNF-a between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention	12 months
Secondary	Change in glucagon-like peptide-1 (GLP-1)	Change in glucagon-like peptide-1 (GLP-1) between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention	12 months
Secondary	Change in peptide YY (PYY)	Change in peptide YY (PYY) between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention	12 months
Secondary	Change in ghrelin	Change in ghrelin between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention	12 months
Secondary	Change in glucose-dependent insulinotropic polypeptide (GIP)	Change in glucose-dependent insulinotropic polypeptide (GIP) between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention	12 months
Secondary	Change in glucagon	Change in glucagon between the two arms (Empagliflozin v/s Placebo) from baseline and after 12 months of intervention	12 months