We investigate the role of empagliflozin in the treatment of obesity in PLWH.

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.

Inclusion Criteria:

• Age >18 years up to 65 years old.
• Body Mass Index (BMI) > 30 kg/m^2.
• Currently receiving an integrase strand transfer inhibitor (INSTI)-based regimen (dolutegravir-based ART).
• Sustained virologic suppression, defined as HIV-1 RNA < 200 copies/mL for at least 6 months.
• Current CD4 count > 250 cells/mL.
• Ability and willingness to provide written informed consent.

Exclusion Criteria:

• Diagnosis of Diabetes Mellitus, defined as a fasting blood glucose level > 126 mg/dL or glycated hemoglobin (HbA1c) > 6.5% (or per ADA definition).
• Renal impairment (e.g., eGFR < 60 ml/min/1.73m^2).
• Active viral hepatitis B or C.
• Hypersensitivity to empagliflozin or any of its excipients.
• Pregnancy or breastfeeding.
• Current use of other SGLT-2 inhibitors.
• Drugs that may interact with empagliflozin (e.g., rifampin or phenytoin) or dolutegravir (e.g., antacids, carbamazepine, or phenytoin).
• Current or recent use of medications known to be associated with significant weight gain (e.g., systemic corticosteroids, antipsychotics, mood stabilizers, or other agents with established weight-promoting effects).
• Known thyroid disease, defined as TSH > 6.0 mIU/L or < 0.35 mIU/L

6 months