Triple-Hormone-Receptor Agonist Retatrutide for Obesity - A Phase 2 Trial.

BACKGROUND: Retatrutide (LY3437943) is an agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and glucagon receptors. Its dose-response relationships with respect to side effects, safety, and efficacy for the treatment of obesity are not known. METHODS: We conducted a phase 2, double-blind, randomized, placebo-controlled trial involving adults who had a body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) of 30 or higher or who had a BMI of 27 to less than 30 plus at least one weight-related condition. Participants were randomly assigned in a 2:1:1:1:1:2:2 ratio to receive subcutaneous retatrutide (1 mg, 4 mg [initial dose, 2 mg], 4 mg [initial dose, 4 mg], 8 mg [initial dose, 2 mg], 8 mg [initial dose, 4 mg], or 12 mg [initial dose, 2 mg]) or placebo once weekly for 48 weeks. The primary end point was the percentage change in body weight from baseline to 24 weeks. Secondary end points included the percentage change in body weight from baseline to 48 weeks and a weight reduction of 5% or more, 10% or more, or 15% or more. Safety was also assessed. RESULTS: We enrolled 338 adults, 51.8% of whom were men. The least-squares mean percentage change in body weight at 24 weeks in the retatrutide groups was -7.2% in the 1-mg group, -12.9% in the combined 4-mg group, -17.3% in the combined 8-mg group, and -17.5% in the 12-mg group, as compared with -1.6% in the placebo group. At 48 weeks, the least-squares mean percentage change in the retatrutide groups was -8.7% in the 1-mg group, -17.1% in the combined 4-mg group, -22.8% in the combined 8-mg group, and -24.2% in the 12-mg group, as compared with -2.1% in the placebo group. At 48 weeks, a weight reduction of 5% or more, 10% or more, and 15% or more had occurred in 92%, 75%, and 60%, respectively, of the participants who received 4 mg of retatrutide; 100%, 91%, and 75% of those who received 8 mg; 100%, 93%, and 83% of those who received 12 mg; and 27%, 9%, and 2% of those who received placebo. The most common adverse events in the retatrutide groups were gastrointestinal; these events were dose-related, were mostly mild to moderate in severity, and were partially mitigated with a lower starting dose (2 mg vs. 4 mg). Dose-dependent increases in heart rate peaked at 24 weeks and declined thereafter. CONCLUSIONS: In adults with obesity, retatrutide treatment for 48 weeks resulted in substantial reductions in body weight. (Funded by Eli Lilly; ClinicalTrials.gov number, NCT04881760.).

Collaborative Care and Healthcare Usage in Families with Pediatric Patients During COVID-19: A Secondary Analysis of National Survey of Children's Health (NSCH) Data.

One of the most detrimental side effects of the COVID-19 pandemic is the needed but not received care. Forgone health care affects the general public, but particularly children with special care needs. Previous research focused on non-modifiable factors, such as demographic background and insurance coverage. Based on Politi and Street's model of collaborative decision-making, we explored how two modifiable communication factors contributed to the prevention of forgone pediatric care during the COVID-19 pandemic. Using a nationally representative sample (n = 10845) from the 2020 National Survey of Children's Health (NSCH) survey, we found that health-care providers' family-centered communication and shared decision-making may reduce the possibility of forgone care through improved satisfaction with providers' communication. For children with mental health needs, providers' family-centered communication may also stimulate family's capacity to openly communicate, leading to better involvement in care and timely health care seeking. This helps to address COVID-related uncertainty, prevent higher health-care expenditures, and reduce negative health outcomes.

Ultrasound evaluation of gastric emptying of high-energy semifluid solid beverage in parturients during labor at term: a randomized controlled trial.

PURPOSE: What to intake during labor is controversial. The purpose of this study was to compare the gastric emptying of high-energy semifluid solid beverage (HESSB) versus that of carbohydrate (CHO) solution of equal calories and volume by evaluating the gastric antral cross-sectional area (CSA) using ultrasonography in parturients during labor at term. METHODS: The study was conducted at a maternity and infant hospital between June and October 2020. Forty parturients scheduled for epidural labor analgesia during labor at term were randomly assigned to receive HESSB (300 mL, n = 20) or CHO (300 mL, n = 20). Gastric antral CSA was measured at baseline and 5, 30, 60, 90, and 120 min after consumption of the drink. The primary outcome was gastric antral CSA at 120 min in the HESSB group and CHO group. RESULTS: The gastric antral CSA between the HESSB group and CHO group at 120 min was not statistically significant (2.73 cm2 ± 0.55 vs. 2.55 cm2 ± 0.72, P = 0.061). All patients returned to baseline at 120 min after intake of 300 mL isocaloric HESSB and CHO, confirmed by evaluation of gastric antral CSA. The visual analog scale score for satiety was higher in the HESSB group (P < 0.001), with better taste satisfaction (7[5-8] vs. 5[4-6], P < 0.001). CONCLUSION: The change of gastric antral cross-sectional area after HESSB is similar to the corresponding calories and volume of CHO and the gastric emptying of HESSB can be emptied within 2 h with better taste satisfaction and satiety in pregnant women under labor analgesia.

A Dual-Process Model of Promoting Employee Mental Health in Crises: Impacts of Leadership Health Support and Organizational Leaders' Crisis Communication in COVID-19.

This study examined how organizations may promote their employees' mental health in difficult times. Drawing from organizational crisis communication and organizational health promotion research, it proposed and tested a dual-process model that links leadership health support, an essential dimension of organizational health culture, with organizational leaders' crisis communication (i.e. use of ethical-base responses) and workers' self-care awareness and perceived stress in a crisis. Through a survey of 502 full-time U.S. employees conducted during COVID-19, we found that organizational leaders' use of ethical-base responses predicted employees' enhanced self-care awareness and decreased stress levels. Further, leadership health support provided a double-buffer effect to sustain employee mental health by directly bolstering employees' self-care awareness and organizational leaders' use of ethical-base responses. The findings of this study bridge the gaps in organizational health promotion and crisis communication literature and offer practical suggestions for organizations seeking to foster employees' mental health challenges during crises.

How Family Sex Talks Can Increase Daughters' Intentions to Engage in Sexual Health Protective Behavior: Mediating Roles of Parents' Direct and Indirect Sexual Communication.

The family environment is essential but underused for promoting sexual and reproductive health protective behaviors (SHPB). However, previous literature had no consistent findings regarding how families can efficiently provide sex education and what aspects of family communication may facilitate SHPB. Based on family communication patterns theory (FCPT) and new research that segments family conformity orientation into four sub-dimensions (i.e., respecting parental authority, experiencing parental control, adopting parents' values, and questioning parents' beliefs), we explored the roles that family communication patterns (FCP) and parents' (direct and indirect) sexual communication play in influencing adult daughters' intentions to engage in SHPB. Using survey data from 234 female participants, path analysis suggested that daughters' SHPB intentions were associated with more direct and indirect sexual communication, higher conversation orientation, higher parental control, and less adoption of parental values. Also, parents' direct sexual communication mediated the impact of conversation orientation on SHPB intentions. Additionally, parents' indirect sexual communication mediated the path from parental value adoption to SHPB intentions, mitigating the negative direct impact of parental value adoption. Theoretical and practical implications are discussed.

Experience of verbal violence among Chinese nursing students in clinical practice: a qualitative study.

BACKGROUND: Workplace violence is prevalent in the nursing profession, and as a relatively junior link of the professional hierarchy, nursing students are not immune to it. Among these, verbal violence may have more serious consequences for the victims than physical violence, but the literature on verbal violence among nursing students in Chinese clinical settings is limited. AIMS: To explore the verbal violence experience among Chinese nursing students in clinical practice, and the strategies used by nursing students to cope with violence. DESIGN: A descriptive qualitative study. METHODS: From January 2022 to June 2022, semi-structured interviews were conducted with 21 nursing students in clinical practice by purposive snowball sampling. Nvivo12 software and inductive content analysis were used for data analysis. This paper followed the COREQ (Consolidated criteria for Reporting Qualitative Research) guidance. RESULTS: Through data analysis, three themes were defined:(1) Multiform verbal violence; (2) Hurting and impacting and (3) Struggling or Coping. The findings indicated that nursing students were subjected to multiple forms of verbal violence in clinical practice, not only from patients and caregivers, but also from peers such as clinical tutors and doctors, which not only harmed students' personal health and well-being, but may also contribute to the nursing industry's future loss of human resources. Seeking emotional support from others and forcing themselves to grow up were the most commonly used coping strategies. CONCLUSION: Nursing educators and nursing managers need to pay attention to verbal violence in the clinical environment, and actively develop the ability of nursing students to deal with uncivilized behavior. Establishing relevant courses and training such as communication, resilience, and violence prevention, establishing a stricter clinical mentor appointment system, and teaching assessment system may be strategies to help nursing students better perform clinical practice.

Trajectory analysis of the work and life experience of healthcare workers during the COVID-19 pandemic: a longitudinal qualitative study.

BACKGROUND: The COVID-19 pandemic has posed a global health threat and has had a profoundly negative impact on the work and lives of healthcare workers. However, few people know how their experiences have evolved over time. AIMS: To describe healthcare workers' experiences during clinical responses to COVID-19 and how they changed over time. DESIGN: A longitudinal qualitative study. METHODS: We undertook a series of four semi-structured qualitative interviews of 14 healthcare workers called as 1st responders to the COVID-19 pandemic. Participants were recruited through purposive snowball sampling. Interviews were undertaken between May 2020 and May 2022 and trajectory approach was used to reveal individual experiences over time. This paper follows the COREQ (Consolidated criteria for Reporting Qualitative Research) guidance. RESULTS: Data analysis yielded the following four themes: (1) Changes in emotions; (2) Changes in organization and management of care; (3) Changes in knowledge and capabilities; and (4) Changes in outlook on life and career. CONCLUSION: Healthcare workers have become stronger in the pandemic and have demonstrated a high degree of professional loyalty and responsibility. However, there is a need to focus on the issue of jealousy and create a harmonious and safe work environment to reduce harm to healthcare workers. Additionally, human resource management strategies must support well-being of healthcare workers and maximize the efficiency of human resource utilization to enable them to respond to current and future needs and emergencies.

Mindfulness-Based Stress Reduction for Quality of Life, Psychological Distress, and Cognitive Emotion Regulation Strategies in Patients With Breast Cancer Under Early Chemotherapy-a Randomized Controlled Trial.

Mindfulness-based interventions (MBIs) have been receiving growing attention in cancer care. This study evaluated the impact of the mindfulness-based stress reduction (MBSR) on quality of life, psychological distress (anxiety and depression), and cognitive emotion regulation strategies in patients with breast cancer under early chemotherapy. A total of 101 patients with breast cancer under early chemotherapy were randomly assigned to either an 8-week MBSR group (n = 50) or a control group (n = 51). The primary outcome was quality of life, measured on Functional Assessment of Cancer Therapy-Breast Cancer. The secondary outcomes were anxiety (Self-rating Anxiety Scale), depression (Self-rating Depression Scale), and cognitive emotion regulation strategies (The Chinese version of Cognitive Emotion Regulation Questionnaire). The participants were assessed at baseline (T0) and week 8 (T1). The data were statistically analyzed by SPSS 21.0. The participants in the MBSR group experienced significantly better outcomes in their quality of life, psychological distress, and cognitive emotion regulation strategies than the control group. The MBSR intervention was demonstrated to improve the positive cognitive emotion regulation strategies and quality of life in patients with breast cancer under early chemotherapy and significantly reduce the patient's anxiety, depression, and negative cognitive emotion regulation strategies, and help the patients to adjust their mental state and promote positive psychology to improve their quality of life.

"I'm walking on eggshells": challenges faced by mothers with breast cancer in interacting with adolescent daughters.

BACKGROUND: With breast cancer becoming the most diagnosed cancer in the world, the number of breast cancer-afflicted mothers with adolescent daughters is also rising. Further, adolescent daughters' mothers serve as role models for in identity formation processes, especially concerning gender and sexuality. Nevertheless, breast cancer threats mother's health, including such a key symbol of her womanhood-the breast-which may adversely affect the development of an adolescent daughter's own sense of personal identity and womanhood. However, few researchers and practitioners have paid attention to mother-daughter interactions in the context of breast cancer. Therefore, this study aimed to uncover the nuances of the interactive challenges with adolescent daughters from breast cancer-afflicted mothers' perspective. METHODS: We conducted a qualitative study following the sample saturation principle, collecting data through semi-structured interviews with 21 breast cancer patients who met the inclusion criteria. We utilized thematic analysis and partially integrated the Foucauldian discourse approach to analyze the data. RESULTS: Three major themes emerged from the data: (1) mothers are lost in chaos (inability to handle the shock of cancer, feelings of powerlessness about the uncertainty of their life span, and confusion about how to respond to daughter's curiosity); (2) mothers struggle to maintain balance (torn between protecting daughters and letting them be independent, and making a tough choice between being a mother or a patient); and (3) mothers are immersed in guilt (increasing daughters' risk of cancer, influencing daughters' development, and imposing burdens on daughters). CONCLUSIONS: Our research explored the interactive experience of breast cancer-afflicted mothers and adolescent daughters. The insights uncovered by this study will help mothers enhance interaction with their daughters and assist health practitioners in devising interventions.

What Satisfies Parents of Pediatric Patients in China: A Grounded Theory Building Analysis of Online Physician Reviews.

Patient satisfaction is an important intermediate outcome of patient-provider encounters, linking face-to-face interactions between patients and medical professionals with patients' well-being after consultations. Today, physician review websites provide a new venue for the study of patient satisfaction, as patients are utilizing such websites to evaluate their encounters with physicians. This study examined how parents of pediatric patients in China evaluated their pediatricians and factors associated with patient satisfaction through a qualitative content analysis of reviews (n = 7230) on the "Good Doctor Website" (haodf.com), China's largest physician review platform. Reviews were chosen from all reviews of pediatricians in eight top-tier hospitals in four major cities. Three dimensions of patient satisfaction were identified: pediatricians' interpersonal manners (including friendliness, listening to patients, heartfelt encouragement, and clear explanation), ethics (including rejecting red envelopes and kickbacks and cost awareness), and medical competence/overall health outcome. This study contributes to a culturally sensitive understanding of patient satisfaction and further explains the tense physician-patient relationship in China. Practically, our findings can inform the training of pediatricians in China.

A unified approach for evaluating the prediction of treatment effect across different types of endpoints.

Phase 2 and 3 development failure is one of the key factors for high drug development cost. Robust prediction of a candidate drug's efficacy and safety profile could potentially improve the success rate of the drug development. Therefore, systematic evaluation of the prediction is important for learning and continuous improvement of the prediction. In this article, we proposed a set of unified criteria that allow to evaluate the predictions across different endpoints, indications and development stages: standardized bias (SB), standardized mean squared errors (SMSE), and credibility of prediction. We applied the SB and SMSE to the predicted treatment effects for 54 comparisons in 5 compounds in immunology and diabetes.

Effects of Mindfulness-Based Stress Reduction Therapy on Posttraumatic Growth and Quality of Life in Patients With Breast Cancer Under Early Chemotherapy: A Randomized Controlled Trial.

Posttraumatic growth (PTG) in patients with breast cancer has been reported. Mindfulness-based stress reduction (MBSR) has been found to be effective in improving the psychological well-being during cancer care. This study aimed to evaluate the impact of MBSR on the levels of PTG, perceived social support, and quality of life. A sample of 101 participants who experienced early chemotherapy enrolled in an MBSR group (n = 50) and a routine care group (n = 51) for 8 weeks. Their postintervention data were combined with preintervention data through a bundle of questionnaires reporting levels of PTG, perceived social support, and quality of life. MBSR showed the prominent validity in raising the levels of PTG and increasing in perceived social support and quality of life from pre- to posttreatment. MBSR improved the levels of PTG, perceived social support, and quality of life in patients with breast cancer in early chemotherapy. In conclusion, MBSR may help to optimize the positive psychological processes that will be targeted to maximize the efficacy of treatment for future cancer survivors.

Ethical dilemmas faced by frontline support nurses fighting COVID-19.

BACKGROUND: In 2019, an outbreak of COVID-19 broke out in Hubei, China. Medical workers from all over the country rushed to Hubei and participated in the treatment and care of COVID-19 patients. These nurses, dedicated to their professional practice, volunteered to provide compassion and expert clinical care during the pandemic. As with other acts of heroism, the ethical dilemmas associated with working on the front line must be considered for future practice. PURPOSE: To explore the ethical dilemmas of frontline nurses of Jiangsu Province in China during deployment to Wuhan to fight the novel coronavirus pneumonia, and to provide a basis for developing strategies to help nursing staff address personal and practice concerns in order to work more effectively during this pandemic and other disasters in the future. RESEARCH DESIGN AND METHOD: Using the phenomenological research method and the purpose sampling method, semi-structured interviews were conducted with 10 nurses, post-deployment to Wuhan, who had worked on the front line to fight the novel coronavirus. ETHICAL CONSIDERATIONS: The research proposal was approved by the Research Ethic Committee of Yangzhou University, China. FINDINGS: From the analysis of the interviews of the 10 participants, three main themes were identified: ethical dilemmas in clinical nursing, ethical dilemmas in interpersonal relationships, and ethical dilemmas in nursing management. CONCLUSION: During a quick response to public health emergencies, where nurses are deployed immediately as a call to action, the issues surrounding ethical dilemmas from several perspectives must be considered. This research suggests that a team approach to proactive planning and open communication during the emergency is an efficient and productive strategy to improve the nurses' experience and sense of well-being.

Mineralization of pH-Sensitive Doxorubicin Prodrug in ZIF-8 to Enable Targeted Delivery to Solid Tumors.

The zeolitic imidazolate framework (ZIF-8), composed of zinc ion and dimethylimidazole, is widely used in drug delivery because of the easy fabrication process and the good biosafety. However, ZIF-8 suffers from low affinity to nonelectric-rich drugs and does not have surface functional groups. Here, to deliver doxorubicin (DOX) with ZIF-8 to specific target sites, DOX was first modified with a pH-sensitive linker containing two carboxyl groups to form the inactive prodrug CAD and subsequently seeded inside ZIF-8 by a 5 min mineralization process. CAD has high affinity to ZIF-8 because of the carboxyl groups and can anchor to the ZIF-8 surface to enable the surface modification with folic acid for tumor targeting. Moreover, the DOX release is precisely controlled by three steps of acidic pH response, with the dissociation of the FA layer, the breakdown of the ZIF-8 structure, and the cleavage of the pH-sensitive linker in prodrug. This novel "prodrug-ZIF-8" strategy has opened a new horizon in drug delivery.

Variable selection for high-dimensional partly linear additive Cox model with application to Alzheimer's disease.

Variable selection has been discussed under many contexts and especially, a large literature has been established for the analysis of right-censored failure time data. In this article, we discuss an interval-censored failure time situation where there exist two sets of covariates with one being low-dimensional and having possible nonlinear effects and the other being high-dimensional. For the problem, we present a penalized estimation procedure for simultaneous variable selection and estimation, and in the method, Bernstein polynomials are used to approximate the involved nonlinear functions. Furthermore, for implementation, a coordinate-wise optimization algorithm, which can accommodate most commonly used penalty functions, is developed. A numerical study is performed for the evaluation of the proposed approach and suggests that it works well in practical situations. Finally the method is applied to an Alzheimer's disease study that motivated this investigation.

The Communicative Ecology of Chinese Patients' Experiences with Health Care.

Patient satisfaction and trust are important intermediate outcomes along pathways linking clinician-patient communication to improve well-being, but they are difficult to achieve in Chinese health care. Problematic physician-patient interactions, questionable health-care organizational practices, and media coverage of medical scandals may have contributed to this problem. Nevertheless, there isscant literature documenting reasons underlying dissatisfaction with Chinese health care. Using Street's ecological model of communication in medical encounters as a conceptual framework, this study explores how media and organizational factors affect Chinese patients' satisfaction and trust both directly and as mediated by the quality of patients' past communication experiences with clinicians. A survey was conducted among 257 Ob-gyn patients in a top-tier hospital in Sichuan, China. The results show that several organizational and media factors, along with patients' experiences with physician communication, predict patient satisfaction and trust. Perceptions of physician communication mediated some of the relationships between organizational and media factors with outcomes. Theoretical and practical implications are discussed, particularly with respect to improving health-care services in China.

A regularized estimation approach for case-cohort periodic follow-up studies with an application to HIV vaccine trials.

This paper discusses regression analysis of the failure time data arising from case-cohort periodic follow-up studies, and one feature of such data, which makes their analysis much more difficult, is that they are usually interval-censored rather than right-censored. Although some methods have been developed for general failure time data, there does not seem to exist an established procedure for the situation considered here. To address the problem, we present a semiparametric regularized procedure and develop a simple algorithm for the implementation of the proposed method. In addition, unlike some existing procedures for similar situations, the proposed procedure is shown to have the oracle property, and an extensive simulation is conducted and it suggests that the presented approach seems to work well for practical situations. The method is applied to an HIV vaccine trial that motivated this study.

Intraoperative infusion of branched-chain amino acids in patients undergoing gastrointestinal tumor surgery.

BACKGROUND: The purpose of this study is to investigate the effects of intraoperative infusion of branched-chain amino acids (BCAA) in patients undergoing gastrointestinal tumor surgery. METHODS: Sixty-one patients with gastrointestinal tumors undergoing gastrointestinal surgery were enrolled and randomly assigned to receive an intraoperative infusion of 3-compound BCAA solution (N = 20), amino acids (AA) solution (N = 21), or normal saline (NS) (N = 20). Nasopharyngeal temperature, blood glucose (BG), plasma insulin, and blood free fatty acids (FFA) concentrations were measured at 30 min before and 10 min after induction (T 0,T 1), 30 min and 2 h after skin incision (T 2,T 3), and 1 h after tracheal extubation (T 4). Intensity of shivering and pain was accessed at 1 h after extubation. RESULTS: The temperature in the BCAA and AA group was significantly higher than that in the NS group at T 4 (P = 0.014 and 0.033). The incidence of shivering in the BCAA and AA group was significantly lower than in the NS group (P = 0.027 and 0.012). BG increased in AA group at T 3 and T 4 (P = 0.001 and 0.045). The plasma insulin concentration increased in the BCAA and AA group from T 1 to T 3. The plasma FFA concentrations in the BCAA group were lower than in the AA and NS group from T 2 to T 4. CONCLUSIONS: Intraoperative BCAA and AA infusion alleviated postoperative hypothermia and shivering. BCAA infusion also inhibited fat mobilization, without adversely affecting blood glucose. TRIAL REGISTRATION: ChiCTR-TRC-14004668.

Let's (not) talk about sexual health: How sexual communication apprehension with healthcare providers and peer communication influence intentions to protect sexual health.

OBJECTIVE: This study examined how patients' clinical and peer interactions may affect their communication apprehension with healthcare providers, a major communication barrier to sexual health protective behaviors (SHPB). METHODS: Between January 2022 and February 2023, we conducted an online survey with 310 participants recruited through snowball sampling. Using structural equation modeling (SEM), we explored relationships among patient-provider interactions, peer communication about sex, communication apprehension with providers, and SHPB intentions. RESULTS: Significant predictors of SHPB intentions included lower communication apprehension and more peer communication. Communication apprehension was a significant mediator in paths from peer communication and three types of patient-provider communication to SHPB intentions. CONCLUSIONS: Our study indicates the need to address communication barriers to increase patients' SHPB intentions. Active patient involvement and patient-centered communication may open up discussions about sex in the clinical setting. Peer interactions, informed by scientific guidance, may reduce patients' apprehension, leading to better health outcomes. PRACTICE IMPLICATIONS: Communication interventions are needed to promote collaborative patient-provider environments and peer sexual communication. Active involvement and evidence-based discussions can help patients navigate difficult conversations (e.g., like sex), improving SHPB.

Triple hormone receptor agonist retatrutide for metabolic dysfunction-associated steatotic liver disease: a randomized phase 2a trial.

Retatrutide is a novel triple agonist of the glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1 and glucagon receptors. A 48-week phase 2 obesity study demonstrated weight reductions of 22.8% and 24.2% with retatrutide 8 and 12 mg, respectively. The primary objective of this substudy was to assess mean relative change from baseline in liver fat (LF) at 24 weeks in participants from that study with metabolic dysfunction-associated steatotic liver disease and ≥10% of LF. Here, in this randomized, double-blind, placebo-controlled trial, participants (n = 98) were randomly assigned to 48 weeks of once-weekly subcutaneous retatrutide (1, 4, 8 or 12 mg dose) or placebo. The mean relative change from baseline in LF at 24 weeks was -42.9% (1 mg), -57.0% (4 mg), -81.4% (8 mg), -82.4% (12 mg) and +0.3% (placebo) (all P < 0.001 versus placebo). At 24 weeks, normal LF (<5%) was achieved by 27% (1 mg), 52% (4 mg), 79% (8 mg), 86% (12 mg) and 0% (placebo) of participants. LF reductions were significantly related to changes in body weight, abdominal fat and metabolic measures associated with improved insulin sensitivity and lipid metabolism. The ClinicalTrials.gov registration is NCT04881760 .