Featured Publications

GLP-1 receptor agonists (GLP-1RAs) such as semaglutide and tirzepatide have transformed obesity care and weight management, delivering unprecedented levels of weight loss in real-world practice. Several studies have demonstrated reversal of weight loss and other cardiometabolic benefits after patients discontinue GLP-1RAs. However, it is not clear whether this reversal is universal or if there are subsets of patients who are more likely to experience continued benefit after their therapeutic exposure. This question has recently been further complicated by the trend for patients to obtain GLP-1RA prescriptions  from other sources such as online providers or medical spas.

Abstract Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have reshaped obesity treatment, yet weight-loss outcomes remain highly uneven in real-world care. Using a federated biomedical platform integrating 23 million de-identified U.S. patient records, we analyzed 135,349 individuals treated with GLP-1RAs and stratified them as “super responders” (>15% weight loss), “moderate responders” (5–15% weight loss), “minimal weight-loss group” (<5% weight loss), and “weight regainers”. super responders reversed nearly two decades of age-associated weight gain in one year, representing approximately a decade more weight reversal than moderate responders. Compared with Wegovy (semaglutide), Zepbound (tirzepatide) showed 47% higher odds (CI: 33–61%) of super-response and 30% lower odds (CI: 23–37%) of minimal weight-loss. Likewise, relative to Ozempic (semaglutide), Mounjaro (tirzepatide) showed 284% (CI: 265–304%) higher odds of super-response and 48% (CI: 46–51%) lower odds of minimal weight-loss. AI-enabled curation processed more than 14 million clinical notes and 15 million structured records covering 1,426 disease terms across the year before and after GLP-1RA initiation. Wegovy and Ozempic super responders showed marked post-treatment increases in vomiting compared with pre-treatment baselines, as reflected by pre-to-post rate ratios (RR 0.37, p=0.014 and RR 0.09, p<0.001). In contrast, Zepbound super responders showed significantly lower post-treatment vomiting relative to baseline (RR 2.34, p<0.001), indicating brand-specific gastrointestinal tolerability profiles. Ozempic (RR 0.24, p<0.001) and Mounjaro (RR 0.17, p<0.001) super responders each showed significant post-treatment increases in diagnoses of protein–energy malnutrition, suggesting a need for whole-body compositional imaging to distinguish beneficial fat loss from unintended lean-mass loss. Novel signals for therapeutic expansion also emerged. Compared with pre-treatment baselines, Zepbound showed significantly reduced post-treatment encounters for recurrent major depressive disorder (pre-to-post RR 12.6, p<0.001) and asthma (pre-to-post RR 2.6, p<0.001). Patient stratification prior to therapy initiation revealed pre-treatment signatures that can guide GLP-1RA choice, with Zepbound super responders showing lower sleep apnea prevalence (baseline RR 0.42, p<0.001) and higher muscle stiffness prevalence (baseline RR 2.4, p=0.037). This study pinpoints actionable physiological signatures and GLP-1RA brand-specific opportunities that emerge from heterogeneous real-world responses, outlining a map for guided precision obesity interventions.

Purpose Teclistamab is initiated with a step-up dosing (SUD) schedule to mitigate the risk of cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). Early teclistamab users commonly received SUD in a hospital setting. This study aimed to evaluate safety and health care resource utilization (HRU) in real-world patients with multiple myeloma who initiated teclistamab SUD in an outpatient setting. Methods This was a retrospective study using Mayo Clinic's electronic medical records from October 26, 2022, to October 31, 2023. Patient characteristics were summarized for all patients treated with teclistamab and separately for patients who started SUD outpatient. SUD pattern, safety, HRU, and post-SUD dosing schedule were described in patients with complete SUD. Results At data cutoff, 65 patients received ≥1 teclistamab dose, including 58 patients who initiated SUD outpatient (median age, 69.2 years; male, 63.8%; White, 89.7%). Among 57 patients who completed SUD in an outpatient setting, all received premedications on the days of teclistamab administrations per label recommendation; 18 (31.6%) developed CRS (13 grade 1, four grade 2, and one grade 4) and two developed ICANS (one each with grade 2 and 4). All CRS and ICANS resolved with supportive care and all patients continued treatment. Eighteen patients were admitted to the hospital for CRS treatment, with a median CRS-related hospital stay of 2 days per admission. Most (60%) doses during SUD required <1 hour clinic time between administration and checkout. Post-SUD, clinic time for treatment doses decreased to <30 minutes for most doses (82%). Conclusion Outcomes of this study support outpatient administration as a safe and feasible option for teclistamab SUD to potentially reduce HRU and improve patient experiences.

Janssen R&D

Conclusions • Treatments for HR+/HER2-low mBC varied, with many patients receiving multiple LOT shortly after 1L and experiencing diminishing time on treatment. Treatment patterns were similar but clinical outcomes shorter in HR+/IHC 0 vs HER2-low disease. • These results highlight a need for effective HER2 targeted therapies that extend duration of clinical benefit earlier in the disease management pathway. • The role of HER2 targeted ADCs in IHC 0 (specifically HER2 null) needs to be further investigated.

Daiichi Sankyo, Inc