Seltorexant Shows Favorable Metabolic Profile, With Celine Goldberger, MD, PhD

Adjunctive seltorexant was associated with less weight gain and more favorable trends in insulin sensitivity than adjunctive quetiapine XR in adults with 

symptoms, according to new metabolic analyses from a 26-week, double-blind, head-to-head study presented at the American College of Neuropsychopharmacology (ACNP) annual meeting from January 12 – 15 at the Bahamas.

The study compared adjunctive seltorexant, an investigational orexin-2 receptor antagonist, with adjunctive quetiapine XR in patients with MDD and clinically significant insomnia symptoms. While earlier results from the trial demonstrated numerically greater response rates and fewer discontinuations due to adverse events with seltorexant, the current analysis focused on metabolic outcomes, an area of particular importance given the high prevalence of cardiometabolic risk in this population.

The study found that body weight changes over 26 weeks were more limited with seltorexant than with quetiapine XR. The mean weight gain was approximately 0.5 kg with seltorexant compared with 2.1 kg with quetiapine XR, representing a 1.6 kg or 3.5 lb difference in 6 months.

“It's very meaningful to patients and can make a difference between patients continuing the drug and discontinuing the drug,” Celine Goldberger, MD, PhD, vice president of global medical affairs at Johnson & Johnson, told 

Metabolic differences extended beyond weight. In participants with baseline metabolic risk, defined by obesity, diabetes, or a homeostatic model assessment of insulin resistance (HOMA-IR) score ≥ 2.9, investigators observed improvement in HOMA-IR and fasting insulin levels with seltorexant. In contrast, quetiapine XR was associated with trends toward worsening. These shifts occurred in the absence of meaningful changes in fasting glucose or hemoglobin A1c, suggesting a potential effect on insulin sensitivity rather than glycemic control.

Furthermore, a greater proportion of patients with baseline insulin resistance transitioned to insulin sensitivity with seltorexant than with quetiapine XR over the 26 weeks. While Goldberger emphasized that these findings are exploratory and warrant further investigation, she noted that insulin resistance is a recognized marker of cardiovascular risk and may be particularly relevant when selecting long-term adjunctive therapies.

“That is [a] very relevant finding that obviously needs to be confirmed, but [a] very interesting thing,” she said.

Goldberger has no relevant reported disclosures.

Wajs E, Trombello JM, Kelly R, et al. Metabolic profiles of participants with major depressive disorder with insomnia symptoms in a phase 3 trial of seltorexant versus quetiapine extended release as adjunctive therapy. Poster presented at American College of Neuropsychopharmacology 64th Annual Meeting 64th annual meeting; January 12-15; Bahamas. Accessed January 19, 2026.

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In a 26-week head-to-head study, adjunctive seltorexant led to less weight gain and improved insulin sensitivity trends compared with quetiapine XR in MDD with insomnia.


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Mishaela Rubin, MD, MS, is a professor of medicine at Columbia University Irving Medical Center.

Mark Warren, MD, FACE is an endocrinologist and clinical associate professor at Campbell University School of Osteopathic Medicine.

Closing Thoughts on Hypoparathyroidism Management

In the final episode, ‘Closing Thoughts on Hypoparathyroidism Management,’ the panelists share their key takeaways from the series discussion on hypoparathyroidism.

Led by the moderator, Dr. Kohlmeier, the panelists, Dr. Rubin, Dr. Warren, and Dr. Al-Dallal, emphasize that PTH-based therapy marks a shift toward physiologic therapy beyond calcium supplementation. They also stress that chronic hypoparathyroidism is a lifelong, multisystem disease requiring individualized care and ongoing research. The panel highlight the need for clear communication with providers, vigilant safety practices, and a medical advocate when possible. Lastly, they describe the era as exciting, noting that meaningful treatment options, such as palopegteriparatide and others in development, will enable truly personalized management plans. Their insights underscore the importance of integrating emerging therapies with comprehensive monitoring to optimize patient outcomes significantly.

Thank you for watching this HCPLive Peer Exchange series on hypoparathyroidism. Please subscribe to our newsletter for information on upcoming video series.

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Emerging Therapies in Hypoparathyroidism

In ‘Emerging Therapies in Hypoparathyroidism,’ our experts delve into three emerging therapies in chronic hypoparathyroidism.

Led by the moderator, Dr. Kohlmeier, the expert endocrinologists, Dr. Rubin, Dr. Warren, and Dr. Al-Dallal, examine the following critical questions:

What are your impressions of emerging therapies, such as eneboparatide (a PTH1R agonist), encaleret (a calcilytic agent), and MBX 2109 (PTH peptide prodrug) for their potential to manage chronic hypoparathyroidism?

The panel evaluates eneboparatide, a PTH1R agonist that closely mimics native parathyroid hormone signaling; MBX 2109, a PTH peptide prodrug engineered for sustained, physiologic PTH exposure; and encaleret, a calcilytic that modulates the calcium‑sensing receptor to enhance endogenous PTH release. Throughout the conversation, the experts provide a comprehensive reflection on the field and the factors that may shape how clinicians approach care moving forward.

Our next episode, ‘Closing Thoughts on Hypoparathyroidism Management,’ wraps up the series with the panelists’ final thoughts on the management of hypoparathyroidism.

In ‘Emerging Therapies in Hypoparathyroidism,’ our experts delve into three emerging therapies in chronic hypoparathyroidism.



Value of Medical Advocates for Patients and Educational Resources for Clinicians in Hypoparathyroidism

In this episode, ‘Value of Medical Advocates for Patients and Educational Resources for Clinicians in Hypoparathyroidism,’ the experts explore the importance of recommending medical advocates or medical alerts to patients as well as educational resources that are available for community providers to better manage hypoparathyroidism.

Led by the moderator, the panelists examine the following critical questions:

Do you recommend that your patients with chronic hypoparathyroidism have a medical advocate as well as a medical alert stating they are ‘Calcium Dependent’, and why is this important?

What other safety measures or educational tools do you recommend?

What educational resources and/or clinical tools would help community primary care providers and specialists better identify and manage chronic hypoparathyroidism?

Throughout the conversation, the experts provide a comprehensive reflection on the field and the factors that may shape how clinicians approach care moving forward.

The next episode in this series, ‘Emerging Therapies in Hypoparathyroidism,’ features the panelists advancing their conversation on hypoparathyroidism and focusing on several emerging therapies and their potential to manage chronic hypoparathyroidism.

In this episode, ‘Value of Medical Advocates for Patients and Educational Resources for Clinicians in Hypoparathyroidism,’ the experts explore the importance of recommending medical advocates or medical alerts to patients as well as educational resources that are available for community providers to better manage hypoparathyroidism.



Multidisciplinary Approaches to Hypoparathyroidism Management

This episode, titled ‘Multidisciplinary Approaches to Hypoparathyroidism Management,’ features expert endocrinologists discussing the role of multidisciplinary collaboration among endocrinologists, nephrologists, and primary care providers.

Do you feel multidisciplinary input can improve outcomes in patients with hypoparathyroidism, and if so, how might we encourage collaboration among endocrinologists, nephrologists, and primary care providers?

How do you encourage adherence and engagement over time in your patients with hypoparathyroidism given they require chronic monitoring and often have several providers?

In the next episode, ‘Value of Medical Advocates for Patients and Educational Resources for Clinicians in Hypoparathyroidism’, panelists will continue their discussion on hypoparathyroidism and highlight the importance of recommending medical advocates or medical alerts for patients as well as additional educational resources for clinicians to better identify and manage hypoparathyroidism.

This episode, titled ‘Multidisciplinary Approaches to Hypoparathyroidism Management,’ features expert endocrinologists discussing the role of multidisciplinary collaboration among endocrinologists, nephrologists, and primary care providers.



Welcome back to another HCPLive Peer Exchange series. In this opening episode, panelists highlight the underlying causes of hypoparathyroidism and the impact of the loss of parathyroid hormone function by examining the following critical questions:

1.	What is chronic hypoparathyroidism, and how is it defined? 
2.	How does the loss of parathyroid hormone (PTH) function disrupt calcium and phosphate homeostasis in hypoparathyroidism? 
3.	What are the causes of chronic hypoparathyroidism, and is there any way to predict or prevent it? When might genetic testing be appropriate?

In the next episode, panelists will continue their discussion on hypoparathyroidism and highlight how it is diagnosed and the key challenges in the diagnosis and monitoring of patients with hypoparathyroidism.

Defining Hypoparathyroidism

The panel discusses the importance of shared decision-making in the care of patients with ATTR-CM. They emphasize that treatment conversations are often ongoing rather than single moments, as patients and families may need time to understand the diagnosis, the goals of therapy, and what to expect over time. The clinicians highlight the role of clear, honest communication, particularly when addressing uncertainty around disease progression or response to therapy.
The group describes how patient preferences can influence treatment selection, including the choice between oral therapies and periodic injections, the desire to minimize medication burden, and the importance of maintaining independence and daily routines. They also note that caregivers are crucial partners in supporting adherence, appointment planning, and monitoring changes in function or symptoms. Ultimately, the panel agrees that successful care depends on making decisions with patients, ensuring they understand their options, and aligning treatment plans with their values, goals, and quality-of-life priorities.


Patient Engagement and Shared Decision-Making in ATTR-CM

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Latest News

Seltorexant Shows Favorable Metabolic Profile, With Celine Goldberger, MD, PhD

Closing Thoughts on Hypoparathyroidism Management

Emerging Therapies in Hypoparathyroidism

Value of Medical Advocates for Patients and Educational Resources for Clinicians in Hypoparathyroidism

Multidisciplinary Approaches to Hypoparathyroidism Management