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

NCT ID: NCT07336797

Last Updated: 2026-01-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 66 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-09-01
• Study Completion Date: 2027-12-30

Brief Summary

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

Detailed Description

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.

Conditions

Metabolic Syndrome; Obesity & Overweight; HIV (Human Immunodeficiency Virus)

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Control Group

Patients in the control group will receive an identical placebo and Standard Antiretroviral Therapy (ART)

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

TDF/FTC+DLG

EMPA Group + SOC

Patients in the intervention arm will receive Empagliflozin 10 mg once daily for 6 months in addition to the standard DTG-based antiretroviral therapy.

Group Type: EXPERIMENTAL

Empagliflozin (oral)

Intervention Type: DRUG

Empagliflozin is an oral medication used primarily to treat type 2 diabetes. It belongs to a class of drugs called SGLT2 inhibitors (sodium-glucose co-transporter 2 inhibitors). Empagliflozin blocks SGLT2 proteins in the kidneys.

This prevents glucose reabsorption, causing excess sugar to be excreted in urine.

It helps lower blood sugar levels and can also reduce body weight and blood pressure.

Interventions

Empagliflozin (oral)

Empagliflozin is an oral medication used primarily to treat type 2 diabetes. It belongs to a class of drugs called SGLT2 inhibitors (sodium-glucose co-transporter 2 inhibitors). Empagliflozin blocks SGLT2 proteins in the kidneys.

This prevents glucose reabsorption, causing excess sugar to be excreted in urine.

It helps lower blood sugar levels and can also reduce body weight and blood pressure.

Intervention Type: DRUG

Placebo

TDF/FTC+DLG

Intervention Type: DRUG

Other Intervention Names

Mellitofix 10 mg; Group A; Inactive Substance

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Abdelrahman Mahmoud

OTHER

Sponsor Role: lead

Responsible Party

Abdelrahman Mahmoud

Teaching and Research Assistant

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Maggie Abbassi, Prof.

Role: STUDY_DIRECTOR

Cairo University

Abedalrahman Dosoky

Role: PRINCIPAL_INVESTIGATOR

Cairo University

Ahmed Kamel

Role: STUDY_DIRECTOR

Cairo University

Locations

Faculty of Pharmacy, Cairo University | Kasr El-Aini, Cairo

Cairo, , Egypt

Site Status: RECRUITING

Countries

Egypt

Central Contacts

Abdelrahman Dosoky, Bachelor's degree

Role: CONTACT

abdelrahman.ibrahim@pharma.cu.edu.eg

+201148534951

Ahmed Kamel, PhD

Role: CONTACT

ahmedm.kamel@pharma.cu.edu.eg

+20 100 676 6275

Facility Contacts

Abdelrahman Dosoky, Bachelor's degree

Role: primary

abdalrahman.mahmoud@pharma.cu.edu.eg

+201148534951

Dosoky

Role: backup

abdalrahman.mahmoud@pharma.cu.edu.eg

Other Identifiers

CL(3828)

Identifier Type: -

Identifier Source: org_study_id