Percent Weight Change Research Articles

Two-year Effect of Semaglutide 2.4 mg Versus Placebo in Adults With Overweight or Obesity: STEP 5

The 2-year efficacy and safety of once-weekly (OW) subcutaneous semaglutide 2.4 mg versus placebo in adults with overweight/obesity was assessed in STEP 5 (NCT03693430). In STEP 5 (phase 3, double-blind, placebo-controlled trial), adults with body mass index (BMI) ≥30 kg/m2, or ≥27 kg/m2 with ≥1 weight-related comorbidity, without diabetes, were randomized 1:1 to 104 weeks’ treatment with OW semaglutide 2.4 mg or placebo. Co-primary endpoints were percent change in body weight (BW) and achievement of ≥5% weight loss.

Relationships Between Blood Pressure Reduction, Weight Loss, and Engagement in a Digital App-Based Hypertension Care Program: Observational Study.

Home blood pressure (BP) monitoring is recommended for people with hypertension; however, meta-analyses have demonstrated that BP improvements are related to additional coaching support in combination with self-monitoring, with little or no effect of self-monitoring alone. High-contact coaching requires substantial resources and may be difficult to deliver via human coaching models. This observational study assessed changes in BP and body weight following participation in a fully digital program called Lark Hypertension Care with coaching powered by artificial intelligence (AI). Participants (N=864) had a baseline systolic BP (SBP) ≥120 mm Hg, provided their baseline body weight, and had reached at least their third month in the program. The primary outcome was the change in SBP at 3 and 6 months, with secondary outcomes of change in body weight and associations of changes in SBP and body weight with participant demographics, characteristics, and program engagement. By month 3, there was a significant drop of -5.4 mm Hg (95% CI -6.5 to -4.3; P<.001) in mean SBP from baseline. BP did not change significantly (ie, the SBP drop maintained) from 3 to 6 months for participants who provided readings at both time points (P=.49). Half of the participants achieved a clinically meaningful drop of ≥5 mm Hg by month 3 (178/349, 51.0%) and month 6 (98/199, 49.2%). The magnitude of the drop depended on starting SBP. Participants classified as hypertension stage 2 had the largest mean drop in SBP of -12.4 mm Hg (SE 1.2 mm Hg) by month 3 and -13.0 mm Hg (SE 1.6 mm Hg) by month 6; participants classified as hypertension stage 1 lowered by -5.2 mm Hg (SE 0.8) mm Hg by month 3 and -7.3 mm Hg (SE 1.3 mm Hg) by month 6; participants classified as elevated lowered by -1.1 mm Hg (SE 0.7 mm Hg) by month 3 but did not drop by month 6. Starting SBP (β=.11; P<.001), percent weight change (β=-.36; P=.02), and initial BMI (β=-.56; P<.001) were significantly associated with the likelihood of lowering SBP ≥5 mm Hg by month 3. Percent weight change acted as a mediator of the relationship between program engagement and drop in SBP. The bootstrapped unstandardized indirect effect was -0.0024 (95% CI -0.0052 to 0; P=.002). A hypertension care program with coaching powered by AI was associated with a clinically meaningful reduction in SBP following 3 and 6 months of program participation. Percent weight change was significantly associated with the likelihood of achieving a ≥5 mm Hg drop in SBP. An AI-powered solution may offer a scalable approach to helping individuals with hypertension achieve clinically meaningful reductions in their BP and associated risk of cardiovascular disease and other serious adverse outcomes via healthy lifestyle changes such as weight loss.

Olanzapine/samidorphan combination consistently mitigates weight gain across various subgroups of patients.

A combination of olanzapine and the opioid receptor antagonist samidorphan (OLZ/SAM) has been approved in the United States for the treatment of adults with schizophrenia or adults with bipolar I disorder. In a phase 3 study in adults with schizophrenia (ENLIGHTEN-2), OLZ/SAM treatment was associated with significantly less weight gain compared with olanzapine. Prespecified subgroup analyses explored the consistency of the weight mitigation effect of OLZ/SAM vs olanzapine across demographic subgroups in ENLIGHTEN-2. The multicenter, randomized, double-blind ENLIGHTEN-2 study (NCT02694328) included outpatients aged 18-55years with a diagnosis of schizophrenia based on DSM-5 criteria, a body mass index (BMI) of 18 to 30kg/m2, and stable body weight (self-reported change ≤5% for ≥3months before study entry). Patients were randomized 1:1 to receive OLZ/SAM or olanzapine for 24weeks. Co-primary endpoints (previously reported) were percent change in body weight and proportion of patients with at least 10% weight gain from baseline at week 24. Prespecified exploratory subgroup analyses by sex, age, self-reported race, and baseline BMI were conducted. At week 24, treatment with OLZ/SAM resulted in numerically less percent weight gain than with olanzapine across all subgroups evaluated. The proportion of patients with at least 10% weight gain was smaller in each subgroup treated with OLZ/SAM vs olanzapine. In these exploratory subgroup analyses from the ENLIGHTEN-2 study, weight-mitigating effects of OLZ/SAM vs olanzapine were observed consistently across patient subgroups and were in line with results from the overall study population.

Biological and Physicochemical Characterization of Self-Adhesive Protective Coating Dental Restorative Material after Incorporation of Antibacterial Nanoparticles.

This study evaluated the physicochemical and antibacterial properties of EQUIATM coat liquid (E) after incorporation of zinc oxide (ZnO) and titanium dioxide (TiO2) nanoparticles. ZnO and TiO2 (1 wt.% and 2 wt.%) were dispersed in EQUIA coat. Principal component analysis (PCA) and cluster analysis were performed to visualize systemic variation. Antibacterial activity was evaluated by colony-forming units and crystal violet staining using Streptococcus mutans and Lactobacillus acidophilus after 24 h, 48 h, and 72 h, and the microstructure was studied by scanning electron microscopy. The weight change was analyzed at 1 and 21 days. The PCA for TiO2- and ZnO-based groups showed 100% variance at all spectral ranges at 600–800/cm and 800–1200/cm, whereas 1200–1800/cm and 2700–3800/cm spectral regions demonstrated 99% variance. The absorbance values were significant (p < 0.05) for both nanoparticles-based adhesives, and the specimens with 2 wt.% ZnO showed the maximum response by minimum bacterial attachment, and the control group showed the least response by maximum attachment. The weight change percentage was reduced after the incorporation of antibacterial nanoparticles. It is suggested that EQUIATM coat containing nanoparticles exhibits promising results, and it may be recommended to clinically use as an improved coating material.

Association Between Mobile Health App Engagement and Weight Loss and Glycemic Control in Adults With Type 2 Diabetes and Prediabetes (D'LITE Study): Prospective Cohort Study.

BackgroundMobile health apps are increasingly used as early intervention to support behavior change for diabetes prevention and control, with the overarching goal of lowering the overall disease burden.ObjectiveThis prospective cohort study conducted in Singapore aimed to investigate app engagement features and their association with weight loss and improved glycemic control among adults with diabetes and prediabetes from the intervention arm of the Diabetes Lifestyle Intervention using Technology Empowerment randomized controlled trial.MethodsDiabetes and prediabetes participants (N=171) with a median age of 52 years, BMI of 29.3 kg/m2, and glycated hemoglobin (HbA1c) level of 6.5% and who were being assigned the Nutritionist Buddy Diabetes app were included. Body weight and HbA1c were measured at baseline, 3 months, and 6 months. A total of 476,300 data points on daily app engagement were tracked via the backend dashboard and developer’s report. The app engagement data were analyzed by quartiles and weekly means expressed in days per week. Linear mixed model analysis was used to determine the associations between the app engagements with percentage weight and HbA1c change.ResultsThe median overall app engagement rate was maintained above 90% at 6 months. Participants who were actively engaged in ≥5 app features were associated with the greatest overall weight reduction of 10.6% from baseline (mean difference −6, 95% CI −8.9 to −3.2; P<.001) at 6 months. Adhering to the carbohydrate limit of >5.9 days per week and choosing healthier food options for >4.3 days per week had the most impact, eliciting weight loss of 9.1% (mean difference −5.2, 95% CI −8.2 to −2.2; P=.001) and 8.8% (mean difference −4.2, 95% CI −7.1 to −1.3; P=.005), respectively. Among the participants with diabetes, those who had a complete meal log for >5.1 days per week or kept within their carbohydrate limit for >5.9 days per week each achieved greater HbA1c reductions of 1.2% (SD 1.3%; SD 1.5%), as compared with 0.2% (SD 1%; SD 0.6%). in the reference groups who used the features <1.1 or ≤2.5 days per week, respectively.ConclusionsHigher app engagement led to greater weight loss and HbA1c reduction among adults with overweight or obesity with type 2 diabetes or prediabetes.Trial RegistrationAustralian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12617001112358; https://anzctr.org.au/Trial/Registration/TrialReview.aspx?ACTRN=12617001112358

Evaluation of the effects of calabash chalk on the haematological profile of Wistar rats

Calabash chalk is a naturally geophagic mineral composed mainly of fossilized seashells or an artificial preparation of a combination of clay, mud, and sand. It is one of the widely consumed earth materials in the practice of geophagia. The present study is aimed at evaluating the effects of oral administration of calabash chalk on haematological parameters and body weight using Wistar rat models. Ten (10) healthy female mice and twenty (20) adults female Wistar rats weighing 20-30 g and 160 -200 g were used for the determination of the LD50 and the experimental study respectively. Locally sourced calabash chalk was orally administered to the Wistar rats at 400, 600 and 800 mg/kg respectively for twenty-eight (28) days. Haematological parameters were determined using a standard automated procedure. The result of the study shows that there was a significant decrease in red blood cell count, haemoglobin concentration, packed cell volume, total white blood cell count, neutrophils, lymphocytes, mid-range absolute and platelet counts among the experimental groups compared to the control (p&lt;0.05). Also, there was a significant reduction in the percentage of weight changes among the experimental animals compared to the control (p&lt;0.05). The present study has shown that despite the wide safety margin of calabash chalk, it can depress haematopoiesis by reducing the red blood cell, white blood cell and platelet counts.

Effect of a Lifestyle Intervention on Cardiometabolic Health Among Emerging Adults

The prevalence of obesity has increased substantially among emerging adults, yet no previous large-scale behavioral weight loss trials have been conducted among this age group. To test the effect of 2 theory-based motivational enhancements on weight loss within a primarily digital lifestyle intervention designed for emerging adults. In this randomized clinical trial conducted at an academic medical research center, 382 participants aged 18 to 25 years with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 25 to 45 were enrolled between February 2, 2016, and February 6, 2019. Data collection was completed February 8, 2020. Analysis was performed on an intention-to-treat basis. Participants were randomized to 1 of 3 groups: developmentally adapted behavioral weight loss (aBWL), aBWL plus behavioral economics (aBWL + BE), or aBWL plus self-determination theory (aBWL + SDT). All groups received a 6-month intervention with 1 group session, 1 individual session, and a digital platform (digital tools for self-monitoring, weekly lessons, tailored feedback, text messages, and optional social media). The aBWL + BE group received modest financial incentives for self-monitoring and weight loss; the aBWL + SDT group received optional experiential classes. Coaching and message framing varied by group. The primary outcome was mean (SE) weight change (in kilograms) at 6 months. Secondary outcomes included proportion of participants achieving weight loss of 5% or more, percentage weight change, waist circumference, body composition, and blood pressure. Among the 382 participants (mean [SD] age, 21.9 [2.2] years), 316 (82.7%) were female, mean (SD) BMI was 33.5 (4.9), 222 (58.1%) were of underrepresented race and/or ethnicity, and 320 (83.8%) were retained at the primary end point. There was a significant time effect for mean (SE) weight loss (-3.22 [0.55] kg in the aBWL group; -3.47 [0.55] kg in the aBWL + BE group; and -3.40 [0.53] kg in the aBWL + SDT group; all P < .001), but no between-group differences were observed (aBWL vs aBWL + BE: difference, -0.25 kg [95% CI, -1.79 to 1.29 kg]; P = .75; aBWL vs aBWL + SDT: difference, -0.18 kg [95% CI, -1.67 to 1.31 kg]; P = .81; and aBWL + SDT vs aBWL + BE: difference, 0.07 kg [95% CI, -1.45 to 1.59 kg]; P = .93). The proportion of participants achieving a weight loss of 5% or more was 40.0% in the aBWL group (50 of 125), 39.8% in the aBWL + BE group (51 of 128), and 44.2% in the aBWL + SDT group (57 of 129), which was not statistically different across groups (aBWL vs aBWL + BE, P = .89; aBWL vs aBWL + SDT, P = .45; aBWL + SDT vs aBWL + BE, P = .54). Parallel findings were observed for all secondary outcomes-clinically and statistically significant improvements with no differences between groups. In this randomized clinical trial, all interventions produced clinically significant benefit, but neither of the motivational enhancements promoted greater reductions in adiposity compared with the developmentally adapted standard group. Continued efforts are needed to optimize lifestyle interventions for this high-risk population and determine which intervention works best for specific individuals based on sociodemographic and/or psychosocial characteristics. ClinicalTrials.gov Identifier: NCT02736981.

A Self-Guided Lifestyle Intervention for Young Men: Findings from the ACTIVATE Randomized Pilot Trial.

Young men are at high risk for developing obesity-related health complications, yet are markedly underrepresented in lifestyle interventions. This pilot study examined the feasibility and preliminary efficacy of a lifestyle intervention (self-guided + health risk messaging) targeting young men. 35 young men (Age = 29.3 ± 4.27; BMI = 30.8 ± 4.26; 34% racial/ethnic minority) were randomly assigned to the intervention or delayed treatment control. The intervention (ACTIVATE) included 1 virtual group session, digital tools (wireless scale, self-monitoring app), access to self-paced content via a secure website, and 12 weekly texts to reinforce health risk messaging. Fasted objective weight was assessed remotely at baseline and 12-weeks. Perceived risk was assessed via survey at baseline, 2-week, and 12-week. T-tests were used to compare weight outcomes between arms. Linear regressions examined the association between percent weight change and perceived risk change. Recruitment was successful as evidenced by 109% of target enrollment achieved in a 2-month period. Retention was 86% at 12 weeks, with no differences by arm (p = 0.17). Participants in the intervention arm experienced modest weight loss at 12 weeks, whereas slight gains were observed in the control arm (-1.6% ± 2.5 vs. +0.31% ± 2.8, p = 0.04). Change in perceived risk was not associated with change in percent weight (p > 0.05). A self-guided lifestyle intervention showed initial promise for weight management among young men, but these findings are limited by small sample size. More research is needed to bolster weight loss outcomes while retaining the scalable self-guided approach. NCT04267263 (https://www.clinicaltrials.gov/ct2/show/NCT04267263).

Results of a 2-year lifestyle intervention for type 2 diabetes: the Reach Ahead for Lifestyle and Health-Diabetes randomized controlled trial.

The Reach Ahead for Lifestyle and Health (REAL HEALTH)-Diabetes study assessed the comparative effectiveness of two Look AHEAD (Action for Health in Diabetes)-adapted lifestyle intervention (LI) arms targeting weight loss in type 2 diabetes compared with medical nutrition therapy (MNT) referral. At 1 year, LI had greater weight loss than MNT. This study reports outcomes at 24 (end of LI) and 36 months. Participants (N=211) with type 2 diabetes and BMI > 25 kg/m2 were randomly assigned to in-person LI, telephone conference call LI, or MNT. The primary outcome was percentage weight change. Secondary outcomes included 5% and 10% weight loss, glycated hemoglobin (HbA1c), and patient-reported outcomes. Participants were 61.7 (SD 10.2) years old; 55% were female; 77% were non-Hispanic White; and had mean (SD) weight of 98 (18.9) kg and mean (SD) HbA1c of 7.7% (1.2%). Mean (SD) weight change at 24 and 36 months was -4.4% (5.9%) and -4.4% (5.4%) in in-person LI, -4.0% (5.8%) and -5.3% (6.4%) in telephone LI, and -3.1% (5.2%) and -5.8% (7.1%) in MNT, with no statistically significant difference in weight or HbA1c at 24 and 36 months. Compared with MNT, LI arms had favorable changes in patient-reported outcomes related to learned dietary skills. There were no differences in weight outcomes among LI participants compared with referral to MNT at the end of intervention or 1 year after its conclusion.

Effects of solriamfetol treatment on body weight in participants with obstructive sleep apnea or narcolepsy

ObjectivesThis analysis characterized changes in weight in participants with obstructive sleep apnea (OSA) or narcolepsy treated with solriamfetol (Sunosi™) 37.5 (OSA only), 75, 150, or 300 mg/d. MethodsIn two 12-week, randomized, placebo-controlled trials and one 1-year open-label extension study, changes in weight were evaluated from baseline to end of study (week 12 or week 40 of the open-label extension [after up to 52 weeks of solriamfetol treatment]) in participants with OSA or narcolepsy. ResultsAfter 12 weeks of solriamfetol treatment, median percent change in weight from baseline across all solriamfetol doses was −0.84%, compared with 0.54% for placebo, in participants with OSA; and −0.07%, compared with 3.08% for placebo, in participants with narcolepsy. After up to 52 weeks of solriamfetol treatment, overall median percent change in weight from baseline was −1.76%, which showed a dose-dependent pattern (75 mg, 0.57%; 150 mg, −1.2%; 300 mg, −2.5%). Results were similar in subgroups of participants with OSA or narcolepsy, with overall median percent changes in weight of −2.2% and −1.1%, respectively. After up to 52 weeks of solriamfetol treatment, the percentage of participants with weight loss ≥5% relative to baseline was 25.7% overall and increased in a dose-dependent manner (75 mg, 4.5%; 150 mg, 17.3%; 300 mg, 32.4%). Results were similar among subgroups of participants with OSA or narcolepsy, with 26.4% and 24.2% of participants experiencing weight loss ≥5%, respectively. No weight-related treatment-emergent adverse events were serious. ConclusionsSolriamfetol treatment was associated with decreases in body weight in a dose-related manner.

Weight loss outcomes achieved by adults accessing an online programme offered as part of Public Health England’s ‘Better Health’ campaign

Effective use of health technology may offer a scalable solution to the obesity pandemic. Online digital programmes provide a convenient and flexible way for more people to access regular support. This service evaluation aims to determine whether adults accessing an online weight management programme via a national campaign are successful in losing weight.Data was analysed for adults registering with Slimming World’s online programme using a discounted membership offered as part of PHE’s ‘Better Health’ campaign between July and December 2020. Last-weight carried forward was used to calculate weight outcomes for participants who had the opportunity to complete 12-weeks and recorded ≥ one weight besides baseline. Engagement was determined using number of online weekly weights recorded with high engagers having weight data for ≥ 9 occasions. Socioeconomic status was assessed using postcode data. Resubscription and uploaded weight data were used to determine numbers who continued beyond the offer period.Twenty-seven thousand two hundred forty-eight adults (5.3% males) with mean age 41.0 ± 11.4 years met inclusion criteria. Mean baseline BMI was 33.4 ± 6.8 kg/m2 (29.2% 30–34.9, 18.3% 35–39.9 and 15.1% > 40 kg/m2). Mean weight loss at 12 weeks was 2.7 (± 3) kg representing a mean loss of 3% (± 3.1) body weight with 42.3% achieving ≥ 3% and 22.1% weight loss ≥ 5%. Median number of weigh-ins was six. Men had greater weight losses compared to women (p < 0.001). High engagers, both men and women, achieved greater weight losses (p < 0.001). Absolute weight loss was associated with joining BMI (rs = -0.15, p < 0.001) but for % weight change only small differences were seen (max effect size = 0.03) with no differences in weight change for high engagers between different baseline BMI categories (p > 0.05). 30.9% were in the lowest two IMD quintiles and absolute and percentage weight change did not differ across deprivation quintiles (p > 0.05). 34.9% continued to access the online support after the offer period.This service evaluation shows that an online programme, offered as part of a national campaign, can offer effective support to a large number of people with different starting BMIs and from different socioeconomic backgrounds. An increased level of engagement leads to better weight losses.

Measured weight loss as a precursor to cancer diagnosis: retrospective cohort analysis of 43302 primary care patients.

BackgroundUnexpected weight loss is a presenting feature of cancer in primary care. Data from primary care are lacking to quantify how much weight loss over what period should trigger further investigation for cancer. This research aimed to quantify cancer diagnosis rates associated with measured weight change in people attending primary care.MethodsRetrospective cohort study of primary care electronic health records data linked to the Surveillance, Epidemiology, and End Results cancer registry (Integrated healthcare delivery system in Washington State, United States). Multivariable Cox regression incorporating time varying covariates using splines to model non‐linear associations (age, percentage weight change, and weight change interval). Fifty thousand randomly selected patients aged 40 years and over followed for up to 9 years (1 January 2006 to 31 December 2014). Outcome measures are hazard ratios (95% confidence intervals) to quantify the association between percentage weight change and cancer diagnosis for all cancers combined, individual cancer sites and stages; percentage risk of cancer diagnosis within 6 months of the end of each weight change episode; and the positive predictive value for cancer diagnosis.ResultsThere were 43 302 included in the analysis after exclusions. Over 287 858 patient‐years of follow‐up, including 24 272 (56.1%) females, 23 980 (55.4%) aged 40 to 59 years, 15 113 (34.9%) 60 to 79 years, and 4209 (9.7%) aged 80 years and over. Adjusted hazard ratios (95% confidence interval) for cancer diagnosis in a 60 years old ranged from 1.04 (1.02 to 1.05, P < 0.001) for 1% weight loss to 1.44 (1.23 to 1.68, P < 0.001) for 10%. An independent linear association was observed between percentage weight loss and increasing cancer risk. The absolute risk of cancer diagnosis increased with increasing age (up to 85 years) and as the weight change measurement interval decreased (<1 year). The positive predictive value for a cancer diagnosis within 1 year of ≥5% measured weight loss in a 60 to 69 years old was 3.41% (1.57% to 6.37%) in men and 3.47% (1.68% to 6.29%) in women. The risk of cancer diagnosis was significantly increased for pancreatic, myeloma, gastro‐oesophageal, colorectal, breast, stage II and IV cancers.ConclusionsWeight loss is a sign of undiagnosed cancer regardless of the interval over which it occurs. Guidelines should resist giving an arbitrary cut‐off for the interval of weight loss and focus on the percentage of weight loss and the patient's age. Future studies should focus on the association between diagnostic evaluation of weight change and risk of cancer mortality.

Effectiveness and cost-effectiveness of text messages with or without endowment incentives for weight management in men with obesity (Game of Stones): study protocol for a randomised controlled trial

BackgroundObesity increases the risk of type 2 diabetes, heart disease, stroke, mobility problems and some cancers, and its prevalence is rising. Men engage less than women in existing weight loss interventions. Game of Stones builds on a successful feasibility study and aims to find out if automated text messages with or without endowment incentives are effective and cost-effective for weight loss at 12 months compared to a waiting list comparator arm in men with obesity.MethodsA 3-arm, parallel group, assessor-blind superiority randomised controlled trial with process evaluation will recruit 585 adult men with body mass index of 30 kg/m2 or more living in and around three UK centres (Belfast, Bristol, Glasgow), purposively targeting disadvantaged areas. Intervention groups: (i) automated, theory-informed text messages daily for 12 months plus endowment incentives linked to verified weight loss targets at 3, 6 and 12 months; (ii) the same text messages and weight loss assessment protocol; (iii) comparator group: 12 month waiting list, then text messages for 3 months. The primary outcome is percentage weight change at 12 months from baseline. Secondary outcomes at 12 months are as follows: quality of life, wellbeing, mental health, weight stigma, behaviours, satisfaction and confidence. Follow-up includes weight at 24 months. A health economic evaluation will measure cost-effectiveness over the trial and over modelled lifetime: including health service resource-use and quality-adjusted life years. The cost-utility analysis will report incremental cost per quality-adjusted life years gained. Participant and service provider perspectives will be explored via telephone interviews, and exploratory mixed methods process evaluation analyses will focus on mental health, multiple long-term conditions, health inequalities and implementation strategies.DiscussionThe trial will report whether text messages (with and without cash incentives) can help men to lose weight over 1 year and maintain this for another year compared to a comparator group; the costs and benefits to the health service; and men’s experiences of the interventions. Process analyses with public involvement and service commissioner input will ensure that this open-source digital self-care intervention could be sustainable and scalable by a range of NHS or public services.Trial registrationISRCTN 91974895. Registered on 14/04/2021.

Tirzepatide Once Weekly for the Treatment of Obesity

BackgroundObesity is a chronic disease that results in substantial global morbidity and mortality. The efficacy and safety of tirzepatide, a novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, in people with obesity are not known.MethodsIn this phase 3 double-blind, randomized, controlled trial, we assigned 2539 adults with a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or more, or 27 or more and at least one weight-related complication, excluding diabetes, in a 1:1:1:1 ratio to receive once-weekly, subcutaneous tirzepatide (5 mg, 10 mg, or 15 mg) or placebo for 72 weeks, including a 20-week dose-escalation period. Coprimary end points were the percentage change in weight from baseline and a weight reduction of 5% or more. The treatment-regimen estimand assessed effects regardless of treatment discontinuation in the intention-to-treat population.ResultsAt baseline, the mean body weight was 104.8 kg, the mean BMI was 38.0, and 94.5% of participants had a BMI of 30 or higher. The mean percentage change in weight at week 72 was −15.0% (95% confidence interval [CI], −15.9 to −14.2) with 5-mg weekly doses of tirzepatide, −19.5% (95% CI, −20.4 to −18.5) with 10-mg doses, and −20.9% (95% CI, −21.8 to −19.9) with 15-mg doses and −3.1% (95% CI, −4.3 to −1.9) with placebo (P<0.001 for all comparisons with placebo). The percentage of participants who had weight reduction of 5% or more was 85% (95% CI, 82 to 89), 89% (95% CI, 86 to 92), and 91% (95% CI, 88 to 94) with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and 35% (95% CI, 30 to 39) with placebo; 50% (95% CI, 46 to 54) and 57% (95% CI, 53 to 61) of participants in the 10-mg and 15-mg groups had a reduction in body weight of 20% or more, as compared with 3% (95% CI, 1 to 5) in the placebo group (P<0.001 for all comparisons with placebo). Improvements in all prespecified cardiometabolic measures were observed with tirzepatide. The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively.ConclusionsIn this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight. (Supported by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.)

A comprehensive approach to predicting weight gain and therapy response in psychopharmacologically treated major depressed patients: A cohort study protocol.

A subgroup of patients with Major Depressive Disorder shows signs of low-grade inflammation and metabolic abberances, while antidepressants can induce weight gain and subsequent metabolic disorders, and lacking antidepressant response is associated with inflammation. A comprehensive investigation of patient phenotypes and their predictive capability for weight gain and treatment response after psychotropic treatment will be performed. The following factors will be analyzed: inflammatory and metabolic markers, gut microbiome composition, lifestyle indicators (eating behavior, physical activity, chronotype, patient characteristics (childhood adversity among others), and polygenic risk scores. Psychiatric inpatients with at least moderate Major Depressive Disorder will be enrolled in a prospective, observational, naturalistic, monocentric study using stratified sampling. Ethical approval was obtained. Primary outcomes at 4 weeks will be percent weight change and symptom score change on the Montgomery Asberg Depression Rating Scale. Both outcomes will also be binarized into clinically relevant outcomes at 5% weight gain and 50% symptom score reduction. Predictors for weight gain and treatment response will be tested using multiple hierachical regression for continuous outcomes, and multiple binary logistic regression for binarized outcomes. Psychotropic premedication, current medication, eating behavior, baseline BMI, age, and sex will be included as covariates. Further, a comprehensive analysis will be carried out using machine learning. Polygenic risk scores will be added in a second step to estimate the additional variance explained by genetic markers. Sample size calculation yielded a total amount of N = 171 subjects. Patient and physician expectancies regarding the primary outcomes and non-random sampling may affect internal validity and external validity, respectively. Through the prospective and naturalistic design, results will gain relevance to clinical practice. Examining the predictive value of patient profiles for weight gain and treatment response during pharmacotherapy will allow for targeted adjustments before and concomitantly to the start of treatment.

Weight Loss and Its Predictors During Participation in Cardiac Rehabilitation

We aimed to assess the prevalence and magnitude of clinically meaningful weight loss among cardiac rehabilitation (CR) participants who were overweight or obese and identify its predictors. We analyzed subjects with body mass index (BMI) ≥25 who were enrolled in a 12-week CR outpatient program from January 1, 2015, to December 31, 2019, and had paired pre- and post-CR weight data. Patients who lost 3% or more of their body weight by the end of the program were compared with the remaining participants. Multivariable logistic regression was used to determine predictors of weight loss. Overall, 129 of 485 subjects (27%) with overweight or obesity reduced their weight by at least 3% (average percent weight change: -5.0% ± 1.8% vs -0.02% ± 2.2%, average weight change: -10.9 ± 5.0 vs -0.1 ± 4.4 pounds, and average BMI change: -1.7 ± 0.7 vs -0.02 ± 0.7 kg/m²). Compared with the remaining 356 patients, those who achieved the defined weight loss were younger (p=0.016) and had higher baseline weight (p=0.002) and BMI (p &lt;0.001). The weight loss group tended to be enrolled more likely for an acute myocardial infarction or percutaneous coronary intervention (p &lt;0.001) and less likely for coronary artery bypass grafting (p=0.001) or a heart valve procedure (p=0.05). By the end of the CR program, the weight loss group demonstrated a greater increase in Rate Your Plate - Heart score (7 [3, 11] vs 4 [1, 8]; p &lt;0.001) and a greater decrease in triglycerides (-20 ± 45 vs -7 ± 55 mg/dL; p=0.026) and glycated hemoglobin (-0.1 [-0.5, 0.1] vs 0.1 [-0.3, 0.4] %; p=0.05, among patients with diabetes or prediabetes). In a multivariable logistic regression model, baseline predictors of clinically meaningful weight loss included higher BMI and not being enrolled for a surgical CR indication (p=0.001). In conclusion, throughout 12 weeks of CR participation, 129 of 485 subjects (27%) with BMI ≥25 had a 3% or more reduction in body weight. Patients with higher baseline BMI and participants without a surgical enrollment diagnosis were more likely to achieve the defined weight loss. Efforts to improve CR referral and enrollment for eligible patients with overweight and obesity should be encouraged, and suitable and efficient weight reduction interventions in CR settings need to be further studied.

Consecutive gain and loss in body weight and waist circumference with risk of subsequent breast cancer in Korean women.

This study investigated the association between longitudinal changes in weight and waist circumference and breast cancer risk according to menopausal status. This retrospective cohort study used data from the population-based Korean National Health Insurance Service (NHI) database. The study population included women aged ≥40 years who consecutively underwent three biennial breast cancer screenings between 2009-2014 and were followed up until 2020. The percentage changes in weight and waist circumference during the three screenings were calculated and categorized into five groups based on the level of increase or decrease in these two factors. Hazard ratios (HRs) and 95% confidence intervals (95% CI) for breast cancer risk were calculated and adjusted for other factors. Of 691,253 premenopausal and 1,519,211 postmenopausal women, 9485 and 12,553 breast cancer cases were identified, respectively, during a median 6.9 follow-up years. Postmenopausal women with two consecutive weight gains had an increased risk of breast cancer risk (HR = 1.11, 95% CI = 1.01 to 1.22); meanwhile, consecutive weight loss was associated with a decreased risk (HR = 0.84, 95% CI = 0.76 to 0.93). Single time and continuous decreases in waist circumference were associated with a decreased risk (HR = 0.91, 95% CI = 0.85 to 0.98, and HR = 0.84, 95% CI = 0.76-0.93), while single time and continuous increases were associated with an increased risk (HR = 1.08, 95% CI = 1.01 to 1.15, and HR = 1.13, 95% CI = 1.04 to 1.22). Single weight gain was associated with the increased breast cancer risk in premenopausal women (HR = 1.07, 95% CI = 1.01 1.13). Our findings suggest a dose-response relationship between weight, waist circumference change, and the risk of future breast cancer.

The Effect of Tailored, Daily, Smartphone Feedback to Lifestyle Self-Monitoring on Weight Loss at 12 Months: the SMARTER Randomized Clinical Trial.

BackgroundSelf-monitoring (SM) is the centerpiece of behavioral weight loss treatment, but the efficacy of smartphone-delivered SM feedback (FB) has not been tested in large, long-term, randomized trials.ObjectiveThe aim of this study was to establish the efficacy of providing remote FB to diet, physical activity (PA), and weight SM on improving weight loss outcomes when comparing the SM plus FB (SM+FB) condition to the SM-only condition in a 12-month randomized controlled trial. The study was a single-site, population-based trial that took place in southwestern Pennsylvania, USA, conducted between 2018 and 2021. Participants were smartphone users age ≥18 years, able to engage in moderate PA, with a mean BMI between 27 and 43 kg/m2.MethodsAll participants received a 90-minute, one-to-one, in-person behavioral weight loss counseling session addressing behavioral strategies, establishing participants’ dietary and PA goals, and instructing on use of the PA tracker (Fitbit Charge 2), smart scale, and diet SM app. Only SM+FB participants had access to an investigator-developed smartphone app that read SM data, in which an algorithm selected tailored messages sent to the smartphone up to 3 times daily. The SM-only participants did not receive any tailored FB based on SM data. The primary outcome was percent weight change from baseline to 12 months. Secondary outcomes included engagement with digital tools (eg, monthly percentage of FB messages opened and monthly percentage of days adherent to the calorie goal).ResultsParticipants (N=502) were on average 45.0 (SD 14.4) years old with a mean BMI of 33.7 (SD 4.0) kg/m2. The sample was 79.5% female (n=399/502) and 82.5% White (n=414/502). At 12 months, retention was 78.5% (n=394/502) and similar by group (SM+FB: 202/251, 80.5%; SM: 192/251, 76.5%; P=.28). There was significant percent weight loss from baseline in both groups (SM+FB: –2.12%, 95% CI –3.04% to –1.21%, P<.001; SM: –2.39%, 95% CI –3.32% to –1.47%; P<.001), but no difference between the groups (–0.27%; 95% CI –1.57% to 1.03%; t =–0.41; P=.68). Similarly, 26.3% (66/251) of the SM+FB group and 29.1% (73/251) of the SM group achieved ≥5% weight loss (chi-square value=0.49; P=.49). A 1% increase in FB messages opened was associated with a 0.10 greater percent weight loss at 12 months (b=–0.10; 95% CI –0.13 to –0.07; t =–5.90; P<.001). A 1% increase in FB messages opened was associated with 0.12 greater percentage of days adherent to the calorie goal per month (b=0.12; 95% CI 0.07-0.17; F=22.19; P<.001).ConclusionsThere were no significant between-group differences in weight loss; however, the findings suggested that the use of commercially available digital SM tools with or without FB resulted in a clinically significant weight loss in over 25% of participants. Future studies need to test additional strategies that will promote greater engagement with digital tools.Trial RegistrationClinicaltrials.gov NCT03367936; https://clinicaltrials.gov/ct2/show/NCT03367936

Myristica Fragrans (Nutmeg) Extract Ameliorated Caffeine-Induced Cardiotoxicity in Male Wistar Rats

Caffeine is the major constituent found in coffee, tea, energy drinks, and chocolate bar among many others. Several studies have reported various effects of caffeine on the cardiovascular system, although there are inconsistencies in these findings. This study, based on these sought to investigate the role of Myristica fragrans on caffeine-induced cardiotoxicity in male Wistar rats. Twenty-five healthy Wistar rats, weighing 130-135 g were randomly assigned into groups (A-E) n=5 each. Group A received 2 mL/kg distilled water as placebo, group B was administered caffeine (40mg/kg), group C received Myristica fragrans only (200mg/kg), group D received caffeine (40mg/kg), and Myristica fragrans (100mg/kg), while group E received caffeine (40mg/kg) and Myristica fragrans (200mg/kg). The rats were orally-gavaged caffeine and Myristica fragrans with the aid of an oral cannula for 21 days. On the 22nd day after the last administration, rats were euthanized sacrificed and the heart tissues were obtained histological procedures. Percentage weight change was significantly decreased (p &lt;0.05), and Lactate dehydrogenase (LDH) activity was significantly increased (p &lt;0.05) in group B relative to the control group. The heart, relative heart weights, and cardiac troponin I were not significantly different (p=0.05) across all experimental groups relative to the control. Assessment of the cardiac histoarchitecture revealed diverse alterations in the caffeine-only group which were ameliorated by administration of 100 and 200 mg/kg Nutmeg extract in groups D and E respectively. Caffeine administration resulted in alteration in cardiac histoarchitecture with 100 and 200mg/kg Myristica fragrans ameliorating these alterations. Nutmeg could serve as a drug lead in the management of cardiac-related conditions.

Impact of the COVID-19 Pandemic on the Effectiveness of a Metabolic Health Telemedicine Intervention for Weight Loss: A Propensity Score Matching Analysis.

BackgroundCoronavirus disease 2019 (COVID-19) pandemic public health measures such as stay-at-home and mandatory work-from-home orders have been associated with obesogenic lifestyle changes, increased risk of weight gain, and their metabolic sequelae. We sought to assess the impact of this pandemic on weight loss from a telemedicine-delivered very-low-carbohydrate intervention targeting nutritional ketosis (NKI).MethodsA total of 746 patients with a BMI ≥25kg/m2, enrolled between January and March 2020 and treated for at least 1 year with the NKI, were classified as pandemic cohort (PC). A separate cohort of 699 patients who received 1 year of the NKI in the preceding years, enrolled between January and March 2018, were identified as pre-pandemic cohort (Pre-PC). Demographic and clinical data were obtained from medical records to compare the cohorts and assess the outcomes. Using propensity score matching (PSM), balanced and matched groups of 407 patients in the Pre-PC and 407 patients in the PC were generated. Longitudinal change in absolute weight and percentage weight change from baseline to 1 year were assessed.ResultsWeight significantly decreased in both PC and Pre-PC at 3, 6, 9, and 12 months. The weight loss trajectory was similar in both PC and Pre-PC with no significant weight differences between the two cohorts at 3, 6, 9, and 12 months. On an average, the PC lost 7.5% body weight while the Pre-PC lost 7.9% over 1 year, and the percent weight loss did not differ between the two cohorts (p = 0.50).ConclusionA very-low-carbohydrate telemedicine intervention delivered comparable and medically significant weight loss independent of pandemic stress and lifestyle limitations.