Mechanistic Insights to Weight Loss Maintenance Through SGLT2 Inhibitors

University of Alabama at Birmingham

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Conditions

Obesity Weight Loss

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

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

Time frame: 12 months

Secondary Outcomes

Change in Body Weight

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

Time frame: 12 months

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

Time frame: 12 months

Change in Waist Circumference

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

Time frame: 12 months

Change in HbA1C levels

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

Time frame: 12 months

Change in lipid profile

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

Time frame: 12 months

Change in HOMA-IR

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

Time frame: 12 months

Change in ESR

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

Time frame: 12 months

Change in CRP

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

Time frame: 12 months

Change in IL-6

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

Time frame: 12 months

Change in TNF-α

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

Time frame: 12 months

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

Time frame: 12 months

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

Time frame: 12 months

Change in ghrelin

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

Time frame: 12 months

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

Time frame: 12 months

Change in glucagon

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

Time frame: 12 months

Mechanistic Insights to Weight Loss Maintenance Through SGLT2 Inhibitors

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes