Mechanistic Insights to Weight Loss Maintenance Through SGLT2 Inhibitors

Mechanistic Insights to Weight Loss Maintenance Through SGLT2 Inhibitors

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.

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