Randomized Trial of Metformin, Ivermectin, and Fluvoxamine for Covid-19.

BACKGROUND: Early treatment to prevent severe coronavirus disease 2019 (Covid-19) is an important component of the comprehensive response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. METHODS: In this phase 3, double-blind, randomized, placebo-controlled trial, we used a 2-by-3 factorial design to test the effectiveness of three repurposed drugs - metformin, ivermectin, and fluvoxamine - in preventing serious SARS-CoV-2 infection in nonhospitalized adults who had been enrolled within 3 days after a confirmed diagnosis of infection and less than 7 days after the onset of symptoms. The patients were between the ages of 30 and 85 years, and all had either overweight or obesity. The primary composite end point was hypoxemia (≤93% oxygen saturation on home oximetry), emergency department visit, hospitalization, or death. All analyses used controls who had undergone concurrent randomization and were adjusted for SARS-CoV-2 vaccination and receipt of other trial medications. RESULTS: A total of 1431 patients underwent randomization; of these patients, 1323 were included in the primary analysis. The median age of the patients was 46 years; 56% were female (6% of whom were pregnant), and 52% had been vaccinated. The adjusted odds ratio for a primary event was 0.84 (95% confidence interval [CI], 0.66 to 1.09; P = 0.19) with metformin, 1.05 (95% CI, 0.76 to 1.45; P = 0.78) with ivermectin, and 0.94 (95% CI, 0.66 to 1.36; P = 0.75) with fluvoxamine. In prespecified secondary analyses, the adjusted odds ratio for emergency department visit, hospitalization, or death was 0.58 (95% CI, 0.35 to 0.94) with metformin, 1.39 (95% CI, 0.72 to 2.69) with ivermectin, and 1.17 (95% CI, 0.57 to 2.40) with fluvoxamine. The adjusted odds ratio for hospitalization or death was 0.47 (95% CI, 0.20 to 1.11) with metformin, 0.73 (95% CI, 0.19 to 2.77) with ivermectin, and 1.11 (95% CI, 0.33 to 3.76) with fluvoxamine. CONCLUSIONS: None of the three medications that were evaluated prevented the occurrence of hypoxemia, an emergency department visit, hospitalization, or death associated with Covid-19. (Funded by the Parsemus Foundation and others; COVID-OUT ClinicalTrials.gov number, NCT04510194.).

Curbing the Obesity Epidemic: Should GLP-1 Receptor Agonists Be the Standard of Care for Obesity?

PURPOSE OF REVIEW: This article summarizes the medical management of obesity with an emphasis on incretin-based therapeutics that target the neuro-hormonal basis of obesity. RECENT FINDINGS: Medications that mimic the effect of incretins, a group of peptide hormones released in response to nutrient intake that regulate appetite, result in potent and durable weight loss. Glucagon-like peptide 1 (GLP-1) agonists and glucose-dependent insulinotropic polypeptide (GIP) agonists such as semaglutide and tirzepatide are approved by the United States Food and Drug Administration (FDA) for the management of obesity. The SELECT trial demonstrated that semaglutide led to a reduction in major adverse cardiovascular events in patients without diabetes who were either overweight and had preexisting cardiovascular disease or obese. SUMMARY: The treatment of obesity is critical to prevent the progression of cardiovascular-kidney-metabolic syndrome. Incretin-based therapies offer remarkable weight loss and reduce major cardiovascular adverse events.

Impact of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccination and Booster on Coronavirus Disease 2019 (COVID-19) Symptom Severity Over Time in the COVID-OUT Trial.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination has decreasing protection from acquiring any infection with emergence of new variants; however, vaccination continues to protect against progression to severe coronavirus disease 2019 (COVID-19). The impact of vaccination status on symptoms over time is less clear. METHODS: Within a randomized trial on early outpatient COVID-19 therapy testing metformin, ivermectin, and/or fluvoxamine, participants recorded symptoms daily for 14 days. Participants were given a paper symptom diary allowing them to circle the severity of 14 symptoms as none (0), mild (1), moderate (2), or severe (3). This is a secondary analysis of clinical trial data on symptom severity over time using generalized estimating equations comparing those unvaccinated, SARS-CoV-2 vaccinated with primary vaccine series only, or vaccine-boosted. RESULTS: The parent clinical trial prospectively enrolled 1323 participants, of whom 1062 (80%) prospectively recorded some daily symptom data. Of these, 480 (45%) were unvaccinated, 530 (50%) were vaccinated with primary series only, and 52 (5%) vaccine-boosted. Overall symptom severity was least for the vaccine-boosted group and most severe for unvaccinated at baseline and over the 14 days (P < .001). Individual symptoms were least severe in the vaccine-boosted group including cough, chills, fever, nausea, fatigue, myalgia, headache, and diarrhea, as well as smell and taste abnormalities. Results were consistent over Delta and Omicron variant time periods. CONCLUSIONS: SARS-CoV-2 vaccine-boosted participants had the least severe symptoms during COVID-19, which abated the quickest over time. Clinical Trial Registration. NCT04510194.

Obesity Management in Cardiometabolic Disease: State of the Art.

PURPOSE OF REVIEW: To summarize research from the last 5 years on the effects of weight loss treatments, including lifestyle changes, anti-obesity medications, and bariatric procedures on cardiovascular disease (CVD) risk factors and CVD outcomes in adults. RECENT FINDINGS: This narrative review includes and summarizes the contemporary evidence of the effects of these different weight loss approaches individually. A literature search was performed using the key words obesity, weight loss, CVD, cardiometabolic, and risk factors and included key clinical trials from the past 5 years. Obesity management through weight loss is associated with improvements in CVD risk factors, such as improved blood pressure, lipid profiles, and glycemic control, with greater weight loss leading to greater improvements in CVD risk factors. Bariatric surgery is associated with greater weight loss than the other procedures and treatments for obesity, and for this, and possibly for other reasons, it is associated with greater reductions in CVD outcomes and mortality. Obesity is an independent risk factor and modulator of other CVD risk factors, and thus, treatment of obesity should be an integral part of management strategies to reduce CVD risk. Future trials and real-world studies of longer duration are needed to inform providers and patients on how to individualize the approach to modifying risks of cardiometabolic disorders through obesity management.

Enhanced Participation in Diabetes Screening and Care After Gestational Diabetes Through Community Health Workers: Results from the Es Mejor Saber Randomized Controlled Trial.

Gestational diabetes mellitus (GDM) is a strong risk factor for type 2 diabetes mellitus, but many women with GDM do not return for postpartum diabetes screening. Interventions utilizing community health workers have demonstrated improvements in health knowledge and participation in other disease settings. The objective of this study was to therefore determine whether bilingual, bicultural community health workers (i.e., promotoras) increase participation in postpartum disease screening and referral for diabetes prevention or care in an urban, low-resource Hispanic community. Ninety-four women with GDM were recruited from the postpartum ward of a safety-net hospital and randomized equally to receive either standard-of-care alone or standard-of-care with a promotora-based intervention consisting of education, appointment reminders, and assistance navigating the healthcare system. Adherence to diabetes screening visits by 12 weeks postpartum and referral for preventive or diabetes care by 18 weeks postpartum was assessed through electronic medical record review. Compared to controls, women in the promotora group completed more diabetes screening visits (74% vs. 96%; relative risk [RR] 3.9; 95% Confidence Interval [CI] 1.1-14.1; p = 0.04). Among those who completed diabetes screening visits, women in the promotora group were also more likely to complete a subsequent referral visit for preventive or diabetes care (17% vs. 83%; RR 4.0; 95% CI 2.1-7.4; p < 0.01). A promotora-based intervention consisting of bilingual, bicultural community health workers improved diabetes screening, prevention, and treatment visits in a resource-limited community of Hispanic women with GDM. ClinicalTrials.gov Identifier: NCT00998595.

The effects of early time restricted eating plus daily caloric restriction compared to daily caloric restriction alone on continuous glucose levels.

Background: The median eating duration in the U.S. is 14.75 h, spread throughout the period of wakefulness and ending before sleep. Food intake at an inappropriate circadian time may lead to adverse metabolic outcomes. Emerging literature suggests that time restricted eating (TRE) may improve glucose tolerance and insulin sensitivity. The aim was to compare 24-h glucose profiles and insulin sensitivity in participants after completing 12 weeks of a behavioral weight loss intervention based on early TRE plus daily caloric restriction (E-TRE+DCR) or DCR alone. Methods: Eighty-one adults with overweight or obesity (age 18-50 years, BMI 25-45 kg/m2) were randomized to either E-TRE+DCR or DCR alone. Each participant wore a continuous glucose monitor (CGM) for 7 days and insulin sensitivity was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) at Baseline and Week 12. Changes in CGM-derived measures and HOMA-IR from Baseline to Week 12 were assessed within and between groups using random intercept mixed models. Results: Forty-four participants had valid CGM data at both time points, while 38 had valid glucose, insulin, HOMA-IR, and hemoglobin A1c (A1c) data at both timepoints. There were no significant differences in sex, age, BMI, or the percentage of participants with prediabetes between the groups (28% female, age 39.2 ± 6.9 years, BMI 33.8 ± 5.7 kg/m2, 16% with prediabetes). After adjusting for weight, there were no between-group differences in changes in overall average sensor glucose, standard deviation of glucose levels, the coefficient of variation of glucose levels, daytime or nighttime average sensor glucose, fasting glucose, insulin, HOMA-IR, or A1c. However, mean amplitude of glycemic excursions changed differently over time between the two groups, with a greater reduction found in the DCR as compared to E-TRE+DCR (p = 0.03). Conclusion: There were no major differences between E-TRE+DCR and DCR groups in continuous glucose profiles or insulin sensitivity 12 weeks after the intervention. Because the study sample included participants with normal baseline mean glucose profiles and insulin sensitivity, the ability to detect changes in these outcomes may have been limited.

Adolescent neurocognitive development, self-regulation, and school-based drug use prevention.

Adolescence is marked by several key development-related changes, including neurocognitive changes. Cognitive abilities associated with self-regulation are not fully developed until late adolescence or early adulthood whereas tendencies to take risks and seek thrilling and novel experience seem to increase significantly throughout this phase, resulting in a discrepancy between increased susceptibility to poor regulation and lower ability to exercise self-control. Increased vulnerability to drug use initiation, maintenance, and dependence during adolescence may be explained based on this imbalance in the self-regulation system. In this paper, we highlight the relevance of schools as a setting for delivering adolescent drug use prevention programs that are based on recent findings from neuroscience concerning adolescent brain development. We discuss evidence from school-based as well as laboratory research that suggests that suitable training may improve adolescents' executive brain functions that underlie self-regulation abilities and, as a result, help prevent drug use and abuse. We note that considerable further research is needed in order (1) to determine that self-regulation training has effects at the neurocognitive level and (2) to effectively incorporate self-regulation training based on neuropsychological models into school-based programming.

Stop the denosumab delay! The effect of implementing an automatic reminder in the electronic medical record.

Delays in denosumab dosing for osteoporosis treatment may lead to rapid bone loss or increased fractures. We assessed the frequency of delayed denosumab dosing before and after the implementation of a structured ordering plan with automated reminders and found that the rate of delayed denosumab dosing was cut in half. PURPOSE: The purpose of our study was to assess the frequency of delayed denosumab dosing before and after the implementation of a structured ordering plan with automated reminders. METHODS: We conducted a retrospective chart review of 720 adults with osteoporosis who received at least two denosumab doses within the UCHealth system before and after the plan went into effect. RESULTS: There was a significant reduction in delayed dosing from 24.0% (PRE) to 12.6% (POST) (p < 0.001) after implementation of the automated reminder. The fraction of delayed denosumab doses due to scheduling issues decreased significantly between PRE and POST time periods (16.4% vs. 3.3%, p = 0.011), while patient-related issues increased from 31.2% to 46.7% (p = 0.041). The rate of provider, medical, and other/unknown issues did not differ between the two time periods. When normalized to patient-years of follow-up, the number of fractures was the same for both groups at 0.016 fractures per patient-year. Fractures in both the PRE and POST groups were related to dosing delays, but the study was not powered to detect the differences in fracture rates between the groups. CONCLUSION: Electronic records with automatic reminders can reduce delayed dosing of denosumab and may lead to reductions in fractures associated with delays.

Early time-restricted eating compared with daily caloric restriction: A randomized trial in adults with obesity.

OBJECTIVE: This trial aimed to evaluate the acceptability and efficacy of early time-restricted eating plus daily caloric restriction (E-TRE+DCR) compared with DCR alone within a behavioral weight-loss intervention. METHODS: Participants (n = 81, 69 women, mean [SD] age: 38.0 [7.8] years, BMI: 34.1 [5.7] kg/m2 ) were randomized to E-TRE (10-hour eating window starting within 3 hours of waking) plus DCR or DCR alone (~35% DCR) for 39 weeks. The primary outcome was body weight (measured with digital scale) at week 12. Secondary outcomes measured at week 12 included hemoglobin A1c, lipids, energy intake (photographic food records), physical activity (accelerometry), dietary adherence (questionnaires), and body composition (dual-energy x-ray absorptiometry). Weight and body composition were also assessed at week 39. RESULTS: Mean [SD] weight loss was not different between groups at week 12 (E-TRE+DCR: -6.2 [4.1] kg vs. DCR: -5.1 [3.2] kg) or at week 39 (E-TRE: -4.9 [5.3] kg vs. DCR: -4.3 [5.3] kg). There were no between-group differences in changes in body composition, dietary adherence, energy intake, physical activity, hemoglobin A1c, or lipids at week 12. CONCLUSIONS: E-TRE+DCR was found to be an acceptable dietary strategy, resulting in similar levels of adherence and weight loss compared with DCR alone.

The effects of the COVID-19 pandemic on weight loss in participants in a behavioral weight-loss intervention.

OBJECTIVE: This study aimed to assess the effects of the COVID-19 pandemic on weight loss, physical activity, and sleep in adults with overweight or obesity participating in a 39-week weight-loss intervention. METHODS: Participants (n = 81, 85% female, mean [SD] age 38.0 [7.8] years, BMI 34.1 [5.7] kg/m2 ) were enrolled in 3 separate cohorts. Cohorts 1 and 2 were studied prior to the pandemic (pre-COVID cohorts). Cohort 3 (COVID cohort) transitioned to a virtual intervention at week 6, when "stay-at-home" orders were implemented in Colorado. Weight was assessed at baseline, week 12, and week 39 with clinic scales before the pandemic and home scales during the pandemic. Diet was assessed with Likert scales at weeks 4, 8, and 12. Physical activity and sleep were assessed at baseline and week 12 with actigraphy. RESULTS: Participants in the COVID cohort reported greater dietary adherence (p = 0.004) and lost more weight than those in the pre-COVID cohorts at week 12 (-7.7 [3.3] kg vs. -3.7 [3.0] kg, p < 0.001) and week 39 (-8.5 [4.4] kg vs. -2.8 [4.6] kg, p < 0.001). Energy intake did not differ between cohorts (p = 0.51). The COVID cohort increased both sedentary time while awake and time in bed at night. CONCLUSIONS: Although the pandemic caused disruptions for the COVID cohort, participants still achieved weight loss with continued behavioral support.

Metformin is Associated with Reduced COVID-19 Severity in Patients with Prediabetes.

Background: With the continuing COVID-19 pandemic, identifying medications that improve COVID-19 outcomes is crucial. Studies suggest that use of metformin, an oral antihyperglycemic, is associated with reduced COVID-19 severity in individuals with diabetes compared to other antihyperglycemic medications. Some patients without diabetes, including those with polycystic ovary syndrome (PCOS) and prediabetes, are prescribed metformin for off-label use, which provides an opportunity to further investigate the effect of metformin on COVID-19. Participants: In this observational, retrospective analysis, we leveraged the harmonized electronic health record data from 53 hospitals to construct cohorts of COVID-19 positive, metformin users without diabetes and propensity-weighted control users of levothyroxine (a medication for hypothyroidism that is not known to affect COVID-19 outcome) who had either PCOS (n = 282) or prediabetes (n = 3136). The primary outcome of interest was COVID-19 severity, which was classified as: mild, mild ED (emergency department), moderate, severe, or mortality/hospice. Results: In the prediabetes cohort, metformin use was associated with a lower rate of COVID-19 with severity of mild ED or worse (OR: 0.630, 95% CI 0.450 - 0.882, p < 0.05) and a lower rate of COVID-19 with severity of moderate or worse (OR: 0.490, 95% CI 0.336 - 0.715, p < 0.001). In patients with PCOS, we found no significant association between metformin use and COVID-19 severity, although the number of patients was relatively small. Conclusions: Metformin was associated with less severe COVID-19 in patients with prediabetes, as seen in previous studies of patients with diabetes. This is an important finding, since prediabetes affects between 19 and 38% of the US population, and COVID-19 is an ongoing public health emergency. Further observational and prospective studies will clarify the relationship between metformin and COVID-19 severity in patients with prediabetes, and whether metformin usage may reduce COVID-19 severity.

Metformin is associated with reduced COVID-19 severity in patients with prediabetes.

AIMS: Studies suggest that metformin is associated with reduced COVID-19 severity in individuals with diabetes compared to other antihyperglycemics. We assessed if metformin is associated with reduced incidence of severe COVID-19 for patients with prediabetes or polycystic ovary syndrome (PCOS), common diseases that increase the risk of severe COVID-19. METHODS: This observational, retrospective study utilized EHR data from 52 hospitals for COVID-19 patients with PCOS or prediabetes treated with metformin or levothyroxine/ondansetron (controls). After balancing via inverse probability score weighting, associations with COVID-19 severity were assessed by logistic regression. RESULTS: In the prediabetes cohort, when compared to levothyroxine, metformin was associated with a significantly lower incidence of COVID-19 with "mild-ED" or worse (OR [95% CI]: 0.636, [0.455-0.888]) and "moderate" or worse severity (0.493 [0.339-0.718]). Compared to ondansetron, metformin was associated with lower incidence of "mild-ED" or worse severity (0.039 [0.026-0.057]), "moderate" or worse (0.045 [0.03-0.069]), "severe" or worse (0.183 [0.077-0.431]), and "mortality/hospice" (0.223 [0.071-0.694]). For PCOS, metformin showed no significant differences in severity compared to levothyroxine, but was associated with a significantly lower incidence of "mild-ED" or worse (0.101 [0.061-0.166]), and "moderate" or worse (0.094 [0.049-0.18]) COVID-19 outcome compared to ondansetron. CONCLUSIONS: Metformin use is associated with less severe COVID-19 in patients with prediabetes or PCOS.

Comparison of weight loss induced by daily caloric restriction versus intermittent fasting (DRIFT) in individuals with obesity: study protocol for a 52-week randomized clinical trial.

BACKGROUND: The standard of care for treating overweight and obesity is daily caloric restriction (DCR). While this approach produces modest weight loss, adherence to DCR declines over time and weight regain is common. Intermittent fasting (IMF) is an alternative dietary strategy for reducing energy intake (EI) that involves >60% energy restriction on 2-3 days per week, or on alternate days, with habitual intake on fed days. While numerous studies have evaluated IMF as a weight loss strategy, there are several limitations including lack of a standard-of-care DCR control, failure to provide guideline-based behavioral support, and failure to rigorously evaluate dietary and PA adherence using objective measures. To date, only three longer-term (52-week) trials have evaluated IMF as a weight loss strategy. None of these longer-duration studies reported significant differences between IMF and DCR in changes in weight. However, each of these studies has limitations that prohibit drawing generalizable conclusions about the relative long-term efficacy of IMF vs. DCR for obesity treatment. METHODS: The Daily Caloric Restriction vs. Intermittent Fasting Trial (DRIFT) is a two-arm, 52-week block randomized (1:1) clinical weight loss trial. The two intervention arms (DCR and IMF) are designed to prescribe an equivalent average weekly energy deficit from baseline weight maintenance energy requirements. Both DCR and IMF will be provided guideline-based behavioral support and a PA prescription. The primary outcome is change in body weight at 52 weeks. Secondary outcomes include changes in body composition (dual-energy x-ray absorptiometry (DXA)), metabolic parameters, total daily energy expenditure (TDEE, doubly labeled water (DLW)), EI (DLW intake-balance method, 7-day diet diaries), and patterns of physical activity (PA, activPAL device). DISCUSSION: Although DCR leads to modest weight loss success in the short-term, there is wide inter-individual variability in weight loss and poor long-term weight loss maintenance. Evidence-based dietary approaches to energy restriction that are effective long-term are needed to provide a range of evidence-based options to individuals seeking weight loss. The DRIFT study will evaluate the long-term effectiveness of IMF vs. DCR on changes in objectively measured weight, EI, and PA, when these approaches are delivered using guideline-based behavioral support and PA prescriptions.

Vaccination Against SARS-CoV-2 Is Associated With a Lower Viral Load and Likelihood of Systemic Symptoms.

Background: Data conflict on whether vaccination decreases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load. The objective of this analysis was to compare baseline viral load and symptoms between vaccinated and unvaccinated adults enrolled in a randomized trial of outpatient coronavirus disease 2019 (COVID-19) treatment. Methods: Baseline data from the first 433 sequential participants enrolling into the COVID-OUT trial were analyzed. Adults aged 30-85 with a body mass index (BMI) ≥25 kg/m2 were eligible within 3 days of a positive SARS-CoV-2 test and <7 days of symptoms. Log10 polymerase chain reaction viral loads were normalized to human RNase P by vaccination status, by time from vaccination, and by symptoms. Results: Two hundred seventy-four participants with known vaccination status contributed optional nasal swabs for viral load measurement: median age, 46 years; median (interquartile range) BMI 31.2 (27.4-36.4) kg/m2. Overall, 159 (58%) were women, and 217 (80%) were White. The mean relative log10 viral load for those vaccinated <6 months from the date of enrollment was 0.11 (95% CI, -0.48 to 0.71), which was significantly lower than the unvaccinated group (P = .01). Those vaccinated ≥6 months before enrollment did not differ from the unvaccinated with respect to viral load (mean, 0.99; 95% CI, -0.41 to 2.40; P = .85). The vaccinated group had fewer moderate/severe symptoms of subjective fever, chills, myalgias, nausea, and diarrhea (all P < .05). Conclusions: These data suggest that vaccination within 6 months of infection is associated with a lower viral load, and vaccination was associated with a lower likelihood of having systemic symptoms.

Postmenopausal Hyperandrogenism: Evaluation and Treatment Strategies.

Evidence of clinical and/or biochemical androgen excess poses a unique differential in postmenopausal women. Some signs and symptoms of postmenopausal hyperandrogenism can be normal and attributed to the natural aging process. However, the causes of androgen excess in this group include both nontumorous and tumorous causes. Treatment of androgen excess may improve both quality of life and long-term metabolic outcomes.

Underreporting of energy intake in weight loss maintainers.

BACKGROUND: Individuals with overweight or obesity commonly underreport energy intake (EI), but it is unknown if the tendency to underreport persists in formerly obese individuals who lose significant weight and maintain their weight loss over long periods of time. OBJECTIVE: Assess the accuracy of self-reported EI in successful weight loss maintainers (WLM) compared with controls of normal body weight (NC) and controls with overweight/obesity (OC). METHODS: Participants for this case-controlled study were recruited in 3 groups: WLM [n = 26, BMI (in kg/m2) 24.1 ± 2.3; maintaining ≥13.6 kg weight loss for ≥1 y], NC (n = 33, BMI 22.7 ± 1.9; similar to current BMI of WLM), and OC (n = 32, BMI 34.0 ± 4.6; similar to pre-weight loss BMI of WLM). Total daily energy expenditure (TDEE) was measured over 7 d using the doubly labeled water (DLW) method, and self-reported EI was concurrently measured from 3-d diet diaries. DLW TDEE and self-reported EI were compared to determine accuracy of self-reported EI. RESULTS: WLM underreported EI (median, interquartile range) (-605, -915 to -314 kcal/d) to a greater degree than NC (-308, -471 to -68 kcal/d; P < 0.01) but not more than OC (-310, -970 to 18 kcal/d; P = 0.21). WLM also showed a greater degree of relative underreporting (-25.3%, -32.9% to -12.5%) compared with NC (-14.3%, -19.6% to -3.1%; P = 0.02) but not OC (-11.2%, -34.1% to -0.7%; P = 0.16). A greater proportion of WLM was classified as underreporters (30.8%) than NC (9.1%; P = 0.05) but not OC (28.1%; P = 1.00). CONCLUSIONS: WLM underreported EI in both absolute and relative terms to a greater extent than NC but not OC. These findings call into question the accuracy of self-reported EI in WLM published in previous studies and align with recent data suggesting that WLM rely less on chronic EI restriction and more on high levels of physical activity to maintain weight loss. This trial was registered at clinicaltrials.gov as NCT03422380.

Multiomic Predictors of Short-Term Weight Loss and Clinical Outcomes During a Behavioral-Based Weight Loss Intervention.

OBJECTIVE: Identifying predictors of weight loss and clinical outcomes may increase understanding of individual variability in weight loss response. We hypothesized that baseline multiomic features, including DNA methylation (DNAme), metabolomics, and gut microbiome, would be predictive of short-term changes in body weight and other clinical outcomes within a comprehensive weight loss intervention. METHODS: Healthy adults with overweight or obesity (n = 62, age 18-55 years, BMI 27-45 kg/m2 , 75.8% female) participated in a 1-year behavioral weight loss intervention. To identify baseline omic predictors of changes in clinical outcomes at 3 and 6 months, whole-blood DNAme, plasma metabolites, and gut microbial genera were analyzed. RESULTS: A network of multiomic relationships informed predictive models for 10 clinical outcomes (body weight, waist circumference, fat mass, hemoglobin A1c , homeostatic model assessment of insulin resistance, total cholesterol, triglycerides, C-reactive protein, leptin, and ghrelin) that changed significantly (P < 0.05). For eight of these, adjusted R2 ranged from 0.34 to 0.78. Our models identified specific DNAme sites, gut microbes, and metabolites that were predictive of variability in weight loss, waist circumference, and circulating triglycerides and that are biologically relevant to obesity and metabolic pathways. CONCLUSIONS: These data support the feasibility of using baseline multiomic features to provide insight for precision nutrition-based weight loss interventions.

Later Meal and Sleep Timing Predicts Higher Percent Body Fat.

Accumulating evidence suggests that later timing of energy intake (EI) is associated with increased risk of obesity. In this study, 83 individuals with overweight and obesity underwent assessment of a 7-day period of data collection, including measures of body weight and body composition (DXA) and 24-h measures of EI (photographic food records), sleep (actigraphy), and physical activity (PA, activity monitors) for 7 days. Relationships between body mass index (BMI) and percent body fat (DXA) with meal timing, sleep, and PA were examined. For every 1 h later start of eating, there was a 1.25 (95% CI: 0.60, 1.91) unit increase in percent body fat (False Discovery Rate (FDR) adjusted p value = 0.010). For every 1 h later midpoint of the eating window, there was a 1.35 (95% CI: 0.51, 2.19) unit increase in percent body fat (FDR p value = 0.029). For every 1 h increase in the end of the sleep period, there was a 1.64 (95% CI: 0.56, 2.72) unit increase in percent body fat (FDR p value = 0.044). Later meal and sleep timing were also associated with lower PA levels. In summary, later timing of EI and sleep are associated with higher body fat and lower levels of PA in people with overweight and obesity.

Impact of Combined Hormonal Contraceptive Use on Weight Loss: A Secondary Analysis of a Behavioral Weight-Loss Trial.

OBJECTIVE: This study aimed to perform a preliminary investigation of the impact of combined hormonal contraceptive (CHC) use on weight loss during an 18-month behavioral weight-loss trial. METHODS: Adults (n = 170; 18-55 years; BMI 27-42 kg/m2 ) received a weight-loss intervention that included a reduced-calorie diet, a progressive exercise prescription, and group-based behavioral support. Premenopausal women (n = 110) were classified as CHC users (CHC, n = 17) or non-CHC users (non-CHC, n = 93). Changes in weight were examined within groups using a linear mixed model, adjusted for age and randomized group assignment. RESULTS: At 6 M, weight was reduced from baseline in both CHC (mean, -6.7 kg; 95% CI: -9.8 to -3.7 kg) and non-CHC (-9.1 kg; -9.1 to -6.4 kg). Between 6 and 18 M, CHC regained weight (4.9 kg; 0.9 to 8.9 kg), while weight remained relatively unchanged in non-CHC (-0.1 kg; -1.8 to 1.6 kg). At 18 M, weight was relatively unchanged from baseline in CHC (-1.8 kg; -7.3 to 3.6 kg) and was reduced from baseline in non-CHC (-7.9 kg; -10.2 to -5.5 kg). CONCLUSIONS: In this secondary data analysis, CHC use was associated with weight regain after initial weight loss. Prospective studies are needed to further understand the extent to which CHC use influences weight loss and maintenance.