Effect of Empagliflozin on Metabolic Outcomes in Adults Living With HIV Receiving Dolutegravir-Based Therapy

HIV remains a major global public health concern. In 2024, approximately 40.8 million people were living with HIV worldwide. Around 630,000 deaths occurred due to AIDS-related illnesses. The preferred first-line ART regimen includes: Tenofovir disoproxil fumarate (TDF)+Emtricitabine (FTC) or Lamivudine (3TC)+Dolutegravir (DTG). The introduction of highly active antiretroviral therapy transformed HIV from a fatal disease into a manageable chronic condition, significantly reducing morbidity and mortality. Integrase strand transfer inhibitors (INSTIs), particularly dolutegravir (DTG), have been associated with greater weight gain compared with non-INSTI antiretroviral regimens. The observed weight gain is strongly linked to adverse metabolic outcomes, including increased incidence of metabolic syndrome, higher rates of insulin resistance, and dyslipidemia. Individuals living with HIV receiving antiretroviral therapy (ART) have been shown to have approximately 1.5-fold higher odds of developing metabolic syndrome (MetS). Over the long term, these alterations contribute to a significantly elevated risk of cardiovascular disease, including myocardial infarction and stroke. Evidence from biopsy-based studies further demonstrates a substantial burden of (NAFLD), (NASH), and liver fibrosis among people living with HIV (PLWH). On the other hand, Sodium-glucose co-transporter-2 (SGLT2) inhibitors have demonstrated: Cardiovascular benefits: Reduction in major adverse cardiovascular events in patients with atherosclerotic disease, including those with hypertension, dyslipidemia, and obesity. Metabolic control: Improved glycemia via renal glucose reabsorption inhibition, lowering hyperglycemia with minimal hypoglycemic risk. Weight and metabolic effects: Reduced body weight, BMI, SBP, visceral adiposity, insulin resistance, improved oral glucose tolerance test (OGTT) values and fasting insulin, even in non-diabetic individuals. Hepatic outcomes: Significant reduction in liver fat content in metabolic disorders, mediated by improved lipid metabolism, insulin sensitivity, and reduced hepatic inflammation, supporting metabolic dysfunction-associated steatotic liver disease (MASLD) management. These combined effects make SGLT2 inhibitors a promising therapeutic option for addressing the multiple facets of metabolic syndrome.