The landscape of metabolic medicine has changed significantly over the past several years, largely driven by the impact of GLP-1 receptor agonists. These therapies have demonstrated meaningful benefits on weight, glycemic control, inflammation and cardiovascular risk. They have also prompted a growing recognition of something psychiatry has long observed but only recently begun to articulate more formally: improving metabolic health often improves mental health as well.
The emergence of WVE-007, an investigational therapy targeting adipose biology through a novel siRNA mechanism, brings new depth to this connection. The early findings from Wave Life Sciences’ Phase 1 INLIGHT trial introduce a therapeutic approach that differs from GLP-1s yet aligns closely with the same metabolic-psychiatric framework that has begun to redefine clinical practice. Understanding how these therapies complement each other is essential as the field moves toward more integrated models of care.
WVE-007 operates very differently from GLP-1 medications. Instead of influencing appetite regulation or gut-brain signaling, it silences the INHBE gene to reduce levels of Activin E, a protein associated with visceral fat storage and cardiometabolic dysfunction. In the Phase 1 trial, a single 240 mg dose of WVE-007 resulted in measurable and clinically relevant improvements in body composition at three months.
Results included a 9.4 percent reduction in visceral fat, a 4.5 percent reduction in total body fat and a 3.2 percent increase in lean mass. These findings were observed without mandated dietary or exercise changes. The therapy was generally well tolerated, and reductions in Activin E were both significant and sustained throughout the assessment period, supporting the possibility of once- or twice-yearly administration.
These outcomes are notable not only within obesity medicine but also within psychiatric care. Visceral fat is closely linked to systemic inflammation, insulin resistance and disruptions in neuroendocrine function. Each of these factors contributes to cognitive impairment, mood instability and reduced treatment responsiveness. A therapy capable of selectively reducing visceral fat while preserving or increasing lean mass introduces meaningful possibilities for improving both physical and mental health outcomes.
The clinical experience with GLP-1 medications has helped illuminate the metabolic-psychiatric connection. These therapies affect more than appetite and gastric motility. GLP-1 receptors are found throughout the central nervous system, including regions responsible for reward processing, emotional regulation, memory and executive functioning. This distribution helps explain why many individuals using GLP-1s report improvements in motivation, cognitive clarity and overall mood.
Emerging research supports these observations. GLP-1 agents demonstrate potential benefits in major depressive disorder, bipolar disorder, cognitive decline and antipsychotic-associated weight gain. Proposed mechanisms include decreased neuroinflammation, improvements in insulin signaling, protection against cellular stress and modulation of glutamatergic pathways.
WVE-007 does not replace GLP-1 therapy. Instead, it expands the available treatment landscape. GLP-1s address appetite regulation, insulin dynamics and gut-brain communication. WVE-007 directly targets adipocyte biology and the distribution of visceral fat. These are separate yet highly interconnected domains of metabolic function.
Wave Life Sciences has already indicated plans to study WVE-007 as both monotherapy and as an add on to GLP-1 medications. This combined approach reflects a broader shift in metabolic medicine: rather than relying on a single mechanism, future treatment strategies may include multiple therapies that work across different metabolic pathways to achieve more comprehensive and sustained benefits.
This approach is particularly relevant in psychiatric populations. Many individuals with serious mental illness experience metabolic disturbances due to chronic stress, systemic inflammation, reduced physical activity and the metabolic effects of psychiatric medications. Interventions capable of addressing these challenges from more than one biological angle may offer significant advantages.
At South Chesapeake Psychiatry, our clinical experience has consistently reflected the connection between metabolic and mental health. Improvements in metabolic health whether through GLP-1 therapy, lifestyle modification or weight focused medication management frequently coincide with clearer thinking, increased energy, reduced anhedonia and more stable emotional regulation. While reductions in body weight contribute to these improvements, the underlying mechanisms are more complex and include changes in inflammatory pathways, insulin sensitivity and central nervous system signaling.
For these reasons, our practice routinely evaluates metabolic factors as part of comprehensive psychiatric care. We work closely with insurers to pursue medical-necessity avenues for evidence based GLP-1 coverage, and we intentionally avoid compounded GLP-1 variants that may pose safety, purity or potency concerns.
Our commitment to understanding and integrating emerging evidence extends to new therapeutics like WVE-007. As research evolves, we remain driven to stay at the forefront of metabolic and psychiatric treatment advancements, ensuring that our patients benefit from the most current, rigorous and effective approaches available.
WVE-007 represents an important development in the broader movement toward understanding mental health through a metabolic lens. Its early results reinforce what GLP-1s have already begun to demonstrate: improving metabolic health can support improvements in cognitive function, mood stability and overall psychiatric well being. As research progresses, therapies targeting visceral fat, inflammation, appetite regulation and adipocyte biology may collectively shape a more comprehensive and effective model of psychiatric care.
This convergence of metabolic and mental health treatment is still unfolding, but the direction is clear. Understanding and addressing the metabolic contributions to psychiatric illness offers a pathway not only to improved physical outcomes but also to more durable and meaningful improvements in mental health.
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