“Weighing In” on GLP-1 Receptor Agonists for People With HIV

Presenter: Suman Srinivasa, MD, MS
The IAS–USA Annual Update on HIV Management in Chicago, Illinois
May 16, 2024





Harnessing GLP-1 Receptor Agonists for Weight Management in HIV Patients: Insights from Dr. Suman Shrinivasa

In a highly anticipated session, Dr. Suman Shrinivasa, Assistant Professor of Medicine and Assistant Director of the Master of Medical Sciences and Clinical Investigation at Harvard Medical School, delivered an insightful presentation on the application of GLP-1 receptor agonists (GLP-1 RAs) in managing weight and metabolic health among individuals living with HIV. Dr. Shrinivasa's extensive background in investigating hormonal contributions to fat redistribution and cardiometabolic diseases positions her as a leading voice in this emerging field.

Understanding GLP-1 Receptor Agonists​

GLP-1 RAs are a class of medications originally developed to manage type 2 diabetes by enhancing insulin secretion and inhibiting glucagon release, thereby lowering blood glucose levels. Beyond their glycemic control, these agents have demonstrated significant weight loss effects, making them attractive for treating obesity. The primary mechanisms driving weight loss include appetite suppression via central nervous system action and delayed gastric emptying, leading to increased satiety.

Common GLP-1 RAs include semaglutide, liraglutide, and dulaglutide, administered primarily through subcutaneous injections. Notably, semaglutide also offers an oral formulation, though currently approved only for diabetes management. These medications are now being explored for broader applications, including weight management and cardiovascular health improvement.

GLP-1 RAs in the General Population​

Clinical trials have established that GLP-1 RAs can reduce A1C levels by 1 to 1.5 points, with semaglutide showing reductions up to 2 points. These medications have also been associated with lower cardiovascular mortality, particularly in patients with pre-existing cardiovascular disease. Additionally, GLP-1 RAs have shown efficacy in reducing visceral fat, a key contributor to metabolic syndrome and cardiovascular risk.

The STEP trial, focusing on weight loss in overweight or obese individuals without diabetes, highlighted semaglutide's superior efficacy compared to liraglutide. Semaglutide participants experienced approximately 16% weight loss versus 6% with liraglutide, underscoring its robust impact on weight management.

Application in HIV Patients​

Weight gain is a known side effect of antiretroviral therapy (ART) initiation in HIV patients, particularly with regimens containing INSTI or TAF. This weight gain poses significant risks, including increased incidence of diabetes, metabolic syndrome, and cardiovascular events. Dr. Shrinivasa's research aims to address these concerns by exploring the role of GLP-1 RAs in mitigating weight gain and improving metabolic outcomes in this population.

Key Findings:

1. Weight Reduction: Retrospective studies involving over 200 HIV-positive individuals, more than half of whom had diabetes, demonstrated an average weight loss of 5 kilograms and a reduction in BMI by 2 points with GLP-1 RA therapy. A separate observational study reported an average weight loss of 6.5 kilograms, with greater efficacy observed in participants with higher BMI.
2. Enhanced Efficacy in HIV: Preliminary randomized controlled trials suggest that GLP-1 RAs may be more effective in HIV-positive patients with diabetes, achieving up to 8% body weight loss compared to smaller reductions in non-HIV counterparts. These findings indicate potential increased efficacy in this specific patient group, though further research is necessary.
3. Improvement in Body Composition: Studies like the SELECT trial have shown that semaglutide not only reduces visceral adipose tissue (VAT) by 27% but also preserves lean body mass relatively better than other weight loss strategies. However, concerns remain regarding the proportionate loss of lean mass, which is crucial for preventing frailty and maintaining muscle function, especially in aging HIV populations.
4. Liver Health and Inflammation: The SLIM Liver study reported significant reductions in liver triglyceride content and inflammatory markers (CRP, IL-6, CD163) among HIV patients treated with GLP-1 RAs, suggesting benefits beyond weight loss, including potential amelioration of fatty liver disease.

Addressing Concerns: Lean Mass Loss and Tolerance​

During the Q&A session, Dr. Shrinivasa addressed concerns about lean body mass loss associated with GLP-1 RAs. While significant fat loss is beneficial, the proportional loss of lean mass—though lower than other weight loss medications—raises questions about its clinical impact. Dr. Shrinivasa emphasized the need for further studies to determine whether this lean mass loss translates to functional deficits or increased frailty, especially in HIV patients who are already at higher risk for sarcopenia.

Clinical Considerations and Future Directions​

Side Effects and Management:GLP-1 RAs are generally well-tolerated, with gastrointestinal side effects like nausea, vomiting, and diarrhea being the most common. Strategies to mitigate these effects include starting at low doses and gradually increasing to minimize discomfort. Additionally, precautions are necessary for patients undergoing anesthesia, as GLP-1 RAs can delay gastric emptying, increasing the risk of aspiration.

Insurance and Accessibility:Access to GLP-1 RAs for weight management can be challenging due to insurance coverage limitations, especially at higher doses required for weight loss rather than glycemic control. Addressing these barriers is crucial for broader application in clinical practice.

Ongoing Research:The evolving landscape of GLP-1 RAs includes combination therapies like dual agonists (e.g., tirzepatide) that target multiple gut hormones for enhanced weight loss and metabolic benefits. Further randomized controlled trials are essential to establish long-term safety, efficacy, and optimal usage protocols in HIV populations.

Conclusion​

Dr. Suman Shrinivasa's presentation sheds light on the promising role of GLP-1 receptor agonists in managing weight and metabolic health among individuals with HIV. While the benefits in weight loss and cardiovascular risk reduction are clear, ongoing research is needed to fully understand the implications of lean mass loss and to optimize treatment strategies for this unique patient population. As GLP-1 RAs continue to demonstrate their multifaceted benefits, they hold significant potential for improving the overall health and quality of life for those living with HIV.