Mean Weight Reduction Research Articles

Abstract 4130929: The Effect of Weight loss and Weight Maintenance on Branch Chain Amino Acid Levels

Introduction: Elevated branch chain amino acid levels (BCAA) have been associated with cardiovascular disease (CVD) and type-2 diabetes. While weight loss has been shown to improve BCAA levels, few studies have evaluated the impact of weight loss and weight maintenance with the OPTIFAST® weight loss program and supervised exercise training. Methods: The present study is a secondary analysis of the PREVAIL-P study. During the weight loss phase, overweight and obese adults (N=30) completed a 10-week OPTIFAST® program with supervised aerobic exercise training with the goal of achieving clinically significant weight loss (≥7%). Participants who met the weight loss goal were randomized to levels of aerobic training consistent with physical activity recommendations (PA-REC) (~550 MET minutes per week) or weight maintenance recommendations (WM-REC) (~970 MET minutes per week) for 18 additional weeks. Valine, leucine, isoleucine and total BCAA levels were measured using nuclear magnetic resonance (NMR) at baseline, after the weight loss phase (10 weeks) and at follow-up (28 Weeks) (LabCorp, Raleigh, NC). Results: Following the weight loss phase, participants had a significant mean reduction in weight (-8.8 kg, p<0.001), total BCAA (-37.4 μmol/L, p<0.001), valine (-15.2 μmol/L, p=0.012), leucine (-20.0 μmol/L, p<0.001), but not isoleucine (-4.1 μmol/L, p=0.214) levels. Improvements in BCAA levels were associated with changes in HDL levels (r=-0.39, p=0.03) and approached significance for visceral fat (r=0.34, p=0.07). Furthermore, changes in BCAA metabolites were not associated with weight, glucose metabolism or other lipid variables for the weight loss phase (p>0.05). In a subset of participants (N=14) who completed the weight maintenance phase (due to COVID pandemic), there were no group differences in the change in total BCAA, valine, leucine between the PA-REC and the WM-REC groups (all ps >0.05). Changes in total BCAA levels (baseline to 28 weeks) were associated with higher mean aerobic exercise training intensity during the intervention (r=-0.64, p=0.013). Conclusion: Weight loss using the OPTIFAST® weight loss program diet combined with aerobic exercise improved BCAA levels, which is associated with decreased CVD risk. Lower BCAA levels during weight maintenance may be influenced by higher exercise intensity exercise. Future studies should evaluate the impact of lifestyle interventions on BCAA levels during long-term weight maintenance.

Abstract 4120229: Shift in body mass index category and associated cardiometabolic risk factors: a post hoc analysis from the SURMOUNT-4 trial

Background: In SURMOUNT-4, participants with obesity demonstrated a mean weight reduction of 21% during the 36-week lead-in with the maximum tolerated dose (MTD) of tirzepatide (TZP). During the 52-week double-blind period, participants who switched to placebo (PBO) experienced a 14% weight regain, while those who continued TZP achieved an additional 6% weight reduction. This post hoc analysis assessed whether participants who shifted to a lower BMI category had improved cardiometabolic factors. Methods: Shift in BMI category (<25 kg/m 2 , 25 to <30 kg/m 2 , 30 to <35 kg/m 2 , 35 to <40 kg/m 2 , and ≥40 kg/m 2 ) from baseline (week 0) during the lead-in period (week 36) and at the primary endpoint (week 88) and from week 36 to week 88 was assessed in participants from SURMOUNT-4 randomized to TZP MTD (N=332) or PBO (N=329). BMI shifts were grouped into “improved” (shift to ≥1 lower category) or “not improved” (stable/attenuated [no change/shift to a higher category]). Changes from baseline in waist circumference, fasting insulin, fasting glucose, HbA1c, vitals and lipid profile were assessed. Results: From weeks 0 to 36, 296 (89%) participants improved in BMI category with TZP, and none had attenuated (Table). From weeks 36 to 88, 130 (39%) participants improved in BMI category with TZP, while the majority (99%) randomized to PBO did not. Overall, from weeks 0 to 88, 304 (92%) vs 189 (57%) participants improved in BMI category with TZP vs PBO, respectively, where the improvements observed in the PBO group originated from the 36-week lead-in period. In general, participants who improved in BMI category at week 88 were noted to have greater improvements in cardiometabolic parameters with TZP vs PBO, including decreases from baseline in waist circumference, fasting insulin, fasting glucose, HbA1c, blood pressure, triglycerides, and cholesterol (total, non-HDL-c, LDL-c, and VLDL-c). Conclusions: In this post hoc analysis of SURMOUNT-4, the majority of TZP-treated participants shifted to lower “improved” BMI categories. Shift to an improved BMI category was accompanied by improved cardiometabolic risk factors, suggesting that TZP treatment may lower further cardiovascular outcomes. Relevant outcomes trials are ongoing.

Effects of pulmonary hypertension targeted therapy on haemodynamics in pulmonary arterial hypertension associated with adult congenital heart disease: a meta-analysis

Abstract Background Pulmonary arterial hypertension (PAH) in adult patients with congenital heart disease (CHD) is associated with increased morbidity and mortality. There is growing evidence that PAH drugs lead to improved hemodynamics, exercise capacity, quality of life and survival in patients with PAH. Purpose The aim of this systematic review and meta-analysis is to evaluate the effects of pulmonary hypertension (PH) medical therapy on the haemodynamic parameters as well as exercise capacity in adult patients with PAH-CHD. Methods PubMed and the Cochrane Library databases have been systematically searched. Meta-analysis was conducted using STATA and Review Manager. Results Fourteen studies including 575 patients were analyzed. Pulmonary haemodynamics improved in patients receiving PH-targeted therapy. The weighted mean reduction in mean pulmonary arterial pressure (mPAP) was -5.8mmHg (I2=0%, 95% CI [–7.55, –4.06], p<0.001).The weighted mean reduction in right atrial pressure (RAP) was -5.81mmHg (I2=0%, 95% CI [-7.55, - 4,07], p<0.001). The weighted mean reduction in pulmonary vascular resistance (PVR) was 358.5dynes/sec/cm-5 (I2 51%, 95% CI [-566.55, -150.46] and p<0.001). Cardiac index was increased by 0.61L/min/m2 (I2=6%, 95% CI [0.23,1.00], p=0.002). Six-minute walking distance increased by 47.26m, (I2=0%, CI [38.36, 56.16], p<0.001). Conclusions PH-targeted therapy improves pulmonary haemodynamics and exercise capacity in adult patients with PAH-CHD.

5184 Tirzepatide Improved Mental and Psychosocial Health-Related Quality of Life in Adults with Obesity or Overweight: Results from the SURMOUNT-4 phase 3 Trial

Abstract Disclosure: T.M. Gibble: Employee; Self; Employment and stockholder, Eli Lilly and Company. D. Cao: Employee; Self; Employment and stockholder, Eli Lilly and Company. M. Murphy: Employee; Self; Employment and stockholder, Eli Lilly and Company. I. Jouravskaya: Employee; Self; Employment and stockholder, Eli Lilly and Company. B. Liao: Employee; Self; Employment and stockholder, Eli Lilly and Company. Background: Tirzepatide is a once weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved in the U.S. for treatment of type 2 diabetes (T2D) and obesity. In the phase 3 SURMOUNT-4 trial with randomized withdrawal of tirzepatide maximum tolerated dose (MTD) after the first 36 weeks, continuing tirzepatide for a total of 88 weeks led to a mean weight reduction of 25.3% from baseline compared to 9.9% for those who switched to placebo (PBO).[1] This analysis evaluated the effect of tirzepatide versus PBO on mental and psychosocial health-related quality of life (HRQoL) outcomes using the SURMOUNT-4 trial data. Methods: Adults (n=783) with body mass index ≥30 or ≥27 kg/m2 and ≥1 obesity-related complication (excluding T2D) were enrolled in an open-label lead-in period to receive tirzepatide once weekly subcutaneously for 36 weeks, escalated to MTD (10 mg or 15 mg). At week (W) 36, 670 participants were randomized 1:1 to continue tirzepatide MTD (n=335) or were switched to PBO (n=335) for 52 weeks. HRQoL was evaluated from W0 to W88 using the Short Form-36 Version 2 Health Survey (SF-36 v2) acute form and Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT), where the last observation before discontinuation was carried forward. Higher scores of SF-36v2 (Mental Component Summary [MCS], role-emotional, and mental health), and IWQOL-Lite-CT (psychosocial composite) reflected better levels of mental function. Least square mean (LSM) changes and estimated treatment differences (ETD) between tirzepatide and PBO were calculated using an analysis of covariance model. Results: LSM changes in mental domain scores for SF-36 v2 and IWQOL-Lite-CT were comparable during lead-in (W0 to W36) between participants randomized to tirzepatide and PBO. Significant improvements were observed from W36 to W88 in SF-36v2 mental domain scores for tirzepatide versus PBO, with LSM scores ( ETD) as follows: MCS, 54.6, 52.9 (1.7, p=0.001); role-emotional, 53.0, 51.1 (1.9, p=0.001), and mental health, 55.4, 52.9 (2.4, p<0.001), respectively. LSM change from W36 to W88 in SF-36 v2 mental domain scores for tirzepatide and PBO were: MCS, 0.1 and -1.6; role-emotional, 0.6 and -1.2, and mental health, 0.3 and -2.1, respectively. Tirzepatide showed significant improvements in IWQOL-Lite-CT psychosocial scores versus PBO from W36 to W88, with LSM scores ( ETD) of 87.7, 75.6 (12.1; p<0.001), respectively. LSM change from W36 to W88 in IWQOL-Lite-CT psychosocial scores for tirzepatide and PBO were 5.1 and -7.0, respectively. Conclusion: In the SURMOUNT-4 trial, adults with overweight or obesity continuing on tirzepatide MTD showed significant and sustained improvements in mental and psychosocial HRQoL compared to those switching to placebo. [1] Sattar N. 59th Annual Meeting European Association for the Study of Diabetes; Oct 2023; Hamburg, Germany. Presentation: 6/1/2024

9229 Tirzepatide Improved Mental and Psychosocial Health-Related Quality of Life in Adults with Obesity or Overweight: Results from the SURMOUNT-4 phase 3 Trial

Abstract Disclosure: T.M. Gibble: Employee; Self; Employment and stockholder, Eli Lilly and Company. D. Cao: Employee; Self; Employment and stockholder, Eli Lilly and Company. M. Murphy: Employee; Self; Employment and stockholder, Eli Lilly and Company. I. Jouravskaya: Employee; Self; Employment and stockholder, Eli Lilly and Company. B. Liao: Employee; Self; Employment and stockholder, Eli Lilly and Company. Background: Tirzepatide is a once weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved in the U.S. for treatment of type 2 diabetes (T2D) and obesity. In the phase 3 SURMOUNT-4 trial with randomized withdrawal of tirzepatide maximum tolerated dose (MTD) after the first 36 weeks, continuing tirzepatide for a total of 88 weeks led to a mean weight reduction of 25.3% from baseline compared to 9.9% for those who switched to placebo (PBO).[1] This analysis evaluated the effect of tirzepatide versus PBO on mental and psychosocial health-related quality of life (HRQoL) outcomes using the SURMOUNT-4 trial data. Methods: Adults (n=783) with body mass index ≥30 or ≥27 kg/m2 and ≥1 obesity-related complication (excluding T2D) were enrolled in an open-label lead-in period to receive tirzepatide once weekly subcutaneously for 36 weeks, escalated to MTD (10 mg or 15 mg). At week (W) 36, 670 participants were randomized 1:1 to continue tirzepatide MTD (n=335) or were switched to PBO (n=335) for 52 weeks. HRQoL was evaluated from W0 to W88 using the Short Form-36 Version 2 Health Survey (SF-36 v2) acute form and Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT), where the last observation before discontinuation was carried forward. Higher scores of SF-36v2 (Mental Component Summary [MCS], role-emotional, and mental health), and IWQOL-Lite-CT (psychosocial composite) reflected better levels of mental function. Least square mean (LSM) changes and estimated treatment differences (ETD) between tirzepatide and PBO were calculated using an analysis of covariance model. Results: LSM changes in mental domain scores for SF-36 v2 and IWQOL-Lite-CT were comparable during lead-in (W0 to W36) between participants randomized to tirzepatide and PBO. Significant improvements were observed from W36 to W88 in SF-36v2 mental domain scores for tirzepatide versus PBO, with LSM scores ( ETD) as follows: MCS, 54.6, 52.9 (1.7, p=0.001); role-emotional, 53.0, 51.1 (1.9, p=0.001), and mental health, 55.4, 52.9 (2.4, p<0.001), respectively. LSM change from W36 to W88 in SF-36 v2 mental domain scores for tirzepatide and PBO were: MCS, 0.1 and -1.6; role-emotional, 0.6 and -1.2, and mental health, 0.3 and -2.1, respectively. Tirzepatide showed significant improvements in IWQOL-Lite-CT psychosocial scores versus PBO from W36 to W88, with LSM scores ( ETD) of 87.7, 75.6 (12.1; p<0.001), respectively. LSM change from W36 to W88 in IWQOL-Lite-CT psychosocial scores for tirzepatide and PBO were 5.1 and -7.0, respectively. Conclusion: In the SURMOUNT-4 trial, adults with overweight or obesity continuing on tirzepatide MTD showed significant and sustained improvements in mental and psychosocial HRQoL compared to those switching to placebo. [1]Sattar N. 59th Annual Meeting European Association for the Study of Diabetes; Oct 2023; Hamburg, Germany. Presentation: 6/1/2024

5183 Tirzepatide Improved Health-Related Quality of Life in People with Obesity or Overweight: Results from SURMOUNT-4 Phase 3 Trial

Abstract Disclosure: T.M. Gibble: Employee; Self; Employment and stockholder, Eli Lilly and Company. D. Cao: Employee; Self; Employment and stockholder, Eli Lilly and Company. M. Murphy: Employee; Self; Employment and stockholder, Eli Lilly and Company. I. Jouravskaya: Employee; Self; Employment and stockholder, Eli Lilly and Company. B. Liao: Employee; Self; Employment and stockholder, Eli Lilly and Company. Background: Tirzepatide is approved in the U.S. for treatment of type 2 diabetes (T2D) and obesity. In the phase 3 SURMOUNT-4 trial with randomized withdrawal of tirzepatide maximum tolerated dose (MTD) after the first 36 weeks, continuing tirzepatide for 88 weeks led to a mean weight reduction of 25.3% from baseline compared to 9.9% for those who switched to placebo (PBO).1 This analysis evaluated the effects of tirzepatide versus PBO on health-related quality of life (HRQoL) outcomes using the SURMOUNT-4 trial data. Methods: Adults (n=783) with body mass index ≥30 or ≥27 kg/m2 and ≥1 obesity-related complication (excluding T2D) were enrolled in an open-label lead-in period to receive tirzepatide once weekly for 36 weeks, escalated to MTD (10 mg or 15 mg). At week (W) 36, 670 participants were randomized 1:1 to continue tirzepatide MTD (n=335) or were switched to PBO (n=335) for 52 weeks. HRQoL was evaluated using Short Form-36 Version 2 Health Survey (SF-36 v2) acute form and Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL-Lite-CT), where last observation before discontinuation was carried forward. Higher scores reflected better levels of functioning. Least square means (LSM) and estimated treatment differences (ETD) between tirzepatide versus PBO were calculated using an analysis of covariance model. Proportion of people achieving clinically meaningful improvement (CMI) in SF-36v2 physical functioning score (change from baseline ≥5.76) was also assessed. Results: LSM changes in SF-36 v2 and IWQOL-Lite-CT scores were comparable during lead-in (W0 to W36) between people randomized to tirzepatide and PBO. Significant improvements were observed from W36 to W88 in SF-36v2 Physical Component Score (PCS), Mental Component Score (MCS), and all domains for tirzepatide versus PBO, with LSM (ETD) as follows: PCS, 54.9, 53.1 (1.8); MCS, 54.6, 52.9 (1.7); physical functioning, 54.2, 51.6 (2.6); role-physical, 54.3, 53.3 (1.1); bodily pain, 54.7, 53.1 (1.6); general health, 56.7, 54.1 (2.6); vitality, 57.0, 55.4 (1.6); social functioning, 54.2, 52.9 (1.3); role-emotional, 53.0, 51.1 (1.9), and mental health, 55.4, 52.9 (2.4), respectively; all p<0.05. Proportion of people achieving CMI (%) in SF-36v2 physical functioning from W0 to W88 was higher for tirzepatide than those who switched to PBO (≥ 5.76, 52.0 and 36.2). Tirzepatide showed significant improvements in IWQOL-Lite-CT scores versus PBO from W36 to W88, with LSM scores (ETD) as follows: total, 86.4, 75.3 (11.1); psychosocial, 87.7, 75.6 (12.1); physical function, 85.7, 76.2 (9.4); and physical, 83.8, 74.7 (9.1), respectively; all p<0.001. Conclusion: In SURMOUNT-4 trial, adults with overweight or obesity continuing on tirzepatide showed significant and sustained improvements in HRQoL versus those switching to PBO. 1Sattar N. 59th Annual Meeting European Association for the Study of Diabetes; Oct 2023; Germany. Presentation: 6/3/2024

Effect of chia seeds or concentrated fish oil on cardiometabolic risk markers in subjects with hypertriglyceridaemia: a parallel clinical trial.

The beneficial effects of n-3 polyunsaturated fatty acids (PUFA) in reducing high blood triglyceride (TG) levels have been well demonstrated. This study aimed to investigate the effect of chia seeds on blood TG and its associated cardiometabolic factors in hypertriglyceridaemic individuals. This three-group randomised controlled trial compared the effects of a low-calorie diet (n = 22), a low-calorie diet with chia seeds (30 g/day, n = 22) or a low-calorie diet with concentrated fish oil (1.8 g/day of n-3 long-chain PUFAs, n = 22) in patients with hypertriglyceridaemia. Anthropometrics, fasting blood lipids, proprotein convertase subtilisin/kexin type 9, insulin, adiponectin, leptin and interleukin-6 levels were measured. After 8 weeks, the mean reduction in weight exhibited by the three groups was not statistically different (2.0, 2.7 and 2.8 kg, respectively, for the control, fish oil and chia seed groups). The plasma TG decreased in both the chia seed and fish oil groups in comparison to the control group (p = 0.001). However, no significant difference was observed between the chia seed and fish oil groups (change from baseline mean: 145.2 and 136.7 mg/dL for the chia seed and fish oil groups, respectively). The consumption of chia seeds was associated with a reduction in diastolic blood pressure (change from baseline mean: 8.4 mmHg) compared to the other two groups. No significant alterations were observed in the other blood biochemical factors between the three groups. In people with moderate hypertriglyceridaemia, a low-calorie diet with 30 g of chia seeds compared to fish oil supplements containing 1.8 g of long-chain PUFAs has a similar effect on reducing plasma TG levels, whereas it has a higher blood pressure-lowering effect.

Theory-Driven Behavioral Obesity Treatment and Carry-Over of Exercise-Related, to Eating-Related, Self-Regulation: Effects on Short- and Long-Term Weight/Waist Circumference Reductions.

The predominant method for treating obesity has been suggesting and providing information on a controlled diet and, to a lesser extent, increased exercise. That approach has largely failed beyond the short term for many decades as obesity rates continue to rise. Therefore, leveraging improvements in psychosocial correlates of weight-loss behaviors has sometimes been suggested instead. The aim of this study was evaluation of targeted improvements in self-regulation and self-efficacy within a theoretically derived weight-loss program. Women with obesity (N = 103) participated in a year-long community-based program emphasizing self-regulatory skills development to counter lifestyle barriers/challenges to first exercise, then controlled eating. Within a structured treatment protocol administered by community facility employees-and based on tenets of social cognitive theory, self-regulation theory, self-efficacy theory, and coaction theory-self-regulatory skills were initially developed to foster adherence to exercise. Those skills were then adapted to promote eating-behavior changes, emphasizing fruit and vegetable intake. Improvements in measures of exercise self-regulation, eating self-regulation, and self-efficacy for controlling eating, their corresponding behaviors, and weight and waist circumference were significant. Greater within-participant carry-over of changes in exercise self-regulation to eating self-regulation was significantly associated with more weight and waist circumference reductions over both 6 and 12 months. Change in eating-related self-efficacy significantly mediated those relationships. The mean weight reduction of approximately 6% indicated positive effects on obesity-related health risks. The community-based setting indicated potentials for large-scale dissemination of theory- and evidence-driven behavioral obesity treatments focused primarily on self-regulatory skills development.

Semaglutide for the management of diabesity: The real-world experience.

Diabesity (diabetes as a consequence of obesity) has emerged as a huge healthcare challenge across the globe due to the obesity pandemic. Judicious use of antidiabetic medications including semaglutide is important for optimal management of diabesity as proven by multiple randomized controlled trials. However, more real-world data is needed to further improve the clinical practice. To study the real-world benefits and side effects of using semaglutide to manage patients with diabesity. We evaluated the efficacy and safety of semaglutide use in managing patients with diabesity in a large academic hospital in the United States. Several parameters were analyzed including demographic information, the data on improvement of glycated hemoglobin (HbA1c), body weight reduction and insulin dose adjustments at 6 and 12 months, as well as at the latest follow up period. The data was obtained from the electronic patient records between January 2019 to May 2023. 106 patients (56 males) with type 2 diabetes mellitus (T2DM), mean age 60.8 ± 11.2 years, mean durations of T2DM 12.4 ± 7.2 years and mean semaglutide treatment for 2.6 ± 1.1 years were included. Semaglutide treatment was associated with significant improvement in diabesity outcomes such as mean weight reductions from baseline 110.4 ± 24.6 kg to 99.9 ± 24.9 kg at 12 months and 96.8 ± 22.9 kg at latest follow up and HbA1c improvement from baseline of 82 ± 21 mmol/mol to 67 ± 20 at 12 months and 71 ± 23 mmol/mol at the latest follow up. An insulin dose reduction from mean baseline of 95 ± 74 units to 76.5 ± 56.2 units was also observed at the latest follow up. Side effects were mild and mainly gastrointestinal like bloating and nausea improving with prolonged use of semaglutide. Semaglutide treatment is associated with significant improvement in diabesity outcomes such as reduction in body weight, HbA1c and insulin doses without major adverse effects. Reviews of largescale real-world data are expected to inform better clinical practice decision making to improve the care of patients with diabesity.

Real-world evaluation of the effects of tirzepatide in patients with type 2 diabetes mellitus.

Tirzepatide is a first-in-class combination glucose-dependent insulinotropic polypeptide (GIP) receptor agonist and glucagon-like peptide 1 receptor agonist (GLP1-RA) approved for treatment of adults with type 2 diabetes mellitus (T2DM) and chronic weight management. The aim of this analysis was to assess the real-world efficacy of tirzepatide in patients with T2DM. This retrospective observational study evaluated patients with T2DM from a large urban academic medical centre who received at least 3 months of continuous tirzepatide treatment. The primary outcome was change in A1C from following tirzepatide treatment. Secondary outcomes included change in body weight and body mass index (BMI) after tirzepatide was initiated. A total of 1896 patient charts were reviewed, and 612 patients were evaluated for the primary outcome. Over a median time period of 10.4 months, treatment with tirzepatide resulted in a mean A1C reduction of 1.02 ± 1.48% (p < 0.001). A total of 570 patients were evaluated for the secondary outcomes. Tirzepatide was associated with a mean reduction in body weight of 7.3 ± 9.3 kg (p < 0.001) and a mean reduction in BMI of 2.5 kg/m2. Greater A1C lowering and weight loss was observed in patients without prior GLP1-RA treatment compared to those switched to tirzepatide from GLP1-RA. In a real-world population of US patients with T2DM, tirzepatide was associated with clinically and statistically significant reductions in A1C and body weight. Greater reductions in both A1C and body weight were observed among patients who were GLP1-RA naïve compared to patients switched from GLP1-RA to tirzepatide.

The Effects of a Novel Deep Breathing Program for Weight Reduction and Cholesterol Metabolism

Background: Previous studies have demonstrated the positive impact of yoga and deep breathing exercises on overall physical wellness. The effects of deep breathing alone on metabolic rate, weight, and cholesterol management have not been studied well. Objective: This study assessed changes in weight and metabolic markers following a 30-day intervention of a 12-minute deep breathing program. Methods: Sixty-six participants with a BMI &gt;27 kg/m2 and 18-70 years were enrolled in this study. Participants were assigned to either the control or intervention group in a single-blinded manner. The intervention group followed the novel deep breathing program, while the control group did not modify their lifestyle or exercise. Anthropometric measurements and metabolic markers were evaluated and compared between the two groups after 30 days. Results: After 30 days, the control group exhibited no significant change in mean weight. The intervention group showed a significant mean weight reduction of 1.3 kg. The intervention group experienced a remarkable average decrease of 22.53 mg/dL in cholesterol levels, while the control group had an increase of 7.2 mg/dL. The 12-minute deep breathing sessions were associated with a significant increase in growth hormone and lung function. It was also associated with decreased glycosylated haemoglobin, creatine, inflammatory markers, and cholesterol levels. Conclusion: A guided deep breathing program can lead to reductions in markers of obesity among clinically overweight patients, even without additional lifestyle modifications. Further investigations are warranted to explore the effects of novel deep breathing programs on metabolic markers and elucidate the underlying mechanisms of weight loss.

Liraglutide for the Treatment of Weight Regain After Bariatric Surgery: A Systematic Review and Meta-analysis.

The efficacy of liraglutide for treating type 2 diabetes mellitus and obesity is well established, but their role in the treatment of weight regain after bariatric surgery remains unclear. We searched PubMed, Embase, and Cochrane Library databases in January 2024. A random-effects model was employed to compute mean differences (MD) and events per 100 observations with 95% confidence intervals (CI) for continuous and binary endpoints. Statistical analysis was performed using R software. A total of 16 studies were included and 881 individuals. Patients were mostly female (50%), aged 36 to 55years, with a mean body mass index (BMI) of 39.4kg/m2, and had BS surgery 5years prior. Over a mean follow-up time ranging from 3months to 4years, it was observed a statistically significant reduction in BMI (MD - 8.56kg/m2; 95% CI 3.34 to 13.79; p < 0.01) and a mean reduction in total weight (MD - 16.03kg; 95% CI 0.03 to 32.02; p = 0.05) after liraglutide use. Additionally, 65% of patients undertaking liraglutide showed total body weight loss (BWL) above 5% (65.8 events per 100 observations; 95% CI 54.96 to 75.20; p < 0.01), while 26% lost more than 10% of total BWL (26.77 events per 100 observations; 95% CI 19.17 to 36.02; p < 0.01). A limitation is a variability between the studies. Our findings support the use of liraglutide for weight management in patients who experience weight regain after BS. Liraglutide is well tolerated and promotes significant weight loss, providing clinicians with a therapeutic option for this clinical challenge.

Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial

In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with preexisting cardiovascular disease, overweight or obesity, without diabetes. Here in this prespecified analysis, we examined effects of semaglutide on weight and anthropometric outcomes, safety and tolerability by baseline body mass index (BMI). In patients treated with semaglutide, weight loss continued over 65 weeks and was sustained for up to 4 years. At 208 weeks, semaglutide was associated with mean reduction in weight (−10.2%), waist circumference (−7.7 cm) and waist-to-height ratio (−6.9%) versus placebo (−1.5%, −1.3 cm and −1.0%, respectively; P < 0.0001 for all comparisons versus placebo). Clinically meaningful weight loss occurred in both sexes and all races, body sizes and regions. Semaglutide was associated with fewer serious adverse events. For each BMI category (<30, 30 to <35, 35 to <40 and ≥40 kg m−2) there were lower rates (events per 100 years of observation) of serious adverse events with semaglutide (43.23, 43.54, 51.07 and 47.06 for semaglutide and 50.48, 49.66, 52.73 and 60.85 for placebo). Semaglutide was associated with increased rates of trial product discontinuation. Discontinuations increased as BMI class decreased. In SELECT, at 208 weeks, semaglutide produced clinically significant weight loss and improvements in anthropometric measurements versus placebo. Weight loss was sustained over 4 years. ClinicalTrials.gov identifier: NCT03574597.

Obesity medications: A narrative review of current and emerging agents

The aim of this narrative review is to synthesize the available data describing the efficacy and safety of medications approved for obesity management and to provide an overview of upcoming agents in development.A literature search of PubMed, Medline, and Embase databases identified relevant articles describing medications approved in the U.S., Australia, U.K., and/or Europe. Papers were selected based on relevance and originality, with phase 3 clinical trials and meta-analyses preferentially included.Six medications are widely approved for long-term weight management in conjunction with lifestyle interventions in people with body mass index (BMI) ≥30 ​kg/m2 or BMI ≥27 ​kg/m2 and at least one medical condition related to excess weight. Compared with lifestyle interventions alone, all medications approved for obesity management are more effective for long-term weight loss and improvements in cardiometabolic risk factors. Older obesity medications are associated with mean weight losses in the range of 5–10%. The new generation of agents, including the injectable incretin analogues semaglutide and tirzepatide are associated with sustained mean weight reductions of 15–20%, along with substantial benefits on a range of health outcomes. Several novel agents are under development, with multi-hormone receptor agonists and oral formulations likely to become available in the coming years.As effective treatment options expand, cost and availability will need to be addressed to enable equitable access to treatment. Other important challenges for clinical practice and research include the need for long-term strategies to prevent and manage weight regain and loss of lean muscle and bone mineral density.

Effectiveness of a hybrid approach in integrating GLP-1 agonists and lifestyle guidance for obesity and pre-diabetes management: RWE retrospective study

AimEmerging anti-obesity pharmacotherapy provides an option to correct maladaptive physiological and hormonal changes associated with obesity. One of the widely used medications in this context is glucagon-like peptide 1 (GLP-1) agonists. However, the misuse of these medications without any guidance and monitoring of lifestyle modifications can lead to unfavorable outcomes. The study aims to evaluate the effectiveness of a hybrid care model, incorporating GLP-1 and GLP-1/GIP agonist therapies, in managing obese patients with/without pre-diabetes. This study showcases the midway results of a 6-month program, which includes a multidisciplinary care team and digital technology for continuous engagement and monitoring of patients, both in-clinic and remotely. MethodsIn a retrospective observational study, 115 participants were treated with GLP-1s (semaglutide, tirzepatide, and liraglutide). Physicians, dietitians, and coaches worked together to support behavioral changes using a dedicated app provided to patients. At the care team end, an integrated portal enabled continuous data flow allowing for the care team to provide personalized care via chat at regular intervals. Data collected included food logs, continuous glucose monitoring (CGM), and digital biomarkers such as sleep and activity. ResultsAt the midpoint of the program, participants exhibited statistically significant improvements in various metabolic parameters. Mean weight reduction was 8 %, with significant reductions in BMI, fat mass, and cholesterol levels. 24 (20.9 %) of patients lost ≥5 % of body weight, 55 (47.8 %) patients lost ≥10 % weight, and 36 (31.3 %) patients lost ≥15 % weight. Sub-analysis of pre-diabetic patients (n=36) demonstrated substantial improvements, including control of pre-diabetes in 80.6 % of cases and reduced HbA1c levels back to normoglycemia (5.39 ± 0.27). ConclusionThe Zone.Health's program, which combines pharmacotherapy with continuous engagement and monitoring to enable sustainable lifestyle modifications, demonstrated significant improvements in weight, body composition, and metabolic markers. Pre-diabetes was also effectively addressed. It is necessary to conduct further research to assess the long-term sustainability and optimal adoption of such care models into clinical practice.

EFFECTS OF A KETOGENIC DIET IN OVERWEIGHT WOMEN WITH POLYCYSTIC OVARY SYNDROME

Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting reproductive-aged women, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. The main objective of the study is to find the effects of a ketogenic diet in overweight women with polycystic ovary syndrome. This prospective interventional study was conducted in a private hospital in Karachi, Pakistan, from June 2023 to Dec 2023. Data was collected from 320 females who were suffering from PCOS. Participants were randomized into two groups: the intervention group (n = 160) received a ketogenic diet, while the control group (n = 160) followed a standard hypocaloric diet. Randomization was performed using computer-generated random numbers to ensure allocation concealment and minimize selection bias. Upon enrollment, participants underwent baseline evaluations to establish their demographic characteristics, medical history, and anthropometric measurements, including weight, BMI, and waist circumference. Data were collected from 320 female patients. In the ketogenic diet (KD) group, participants had a mean age of 28.1±4.2 years and a mean BMI of 30.01±2.3 kg/m2. Their waist circumference averaged 90.1±5.0cm, with a fasting glucose level of 110±10 mg/dL and a DHEAS level of 350±50 μg/dL. In the ketogenic diet (KD) group, participants experienced a mean reduction in body weight of 8.5±2.3kg, a decrease in BMI of 3.2±1.1Kg/m2, and a reduction in waist circumference of 10±4cm. Conversely, the control group exhibited a mean decrease in body weight of 2.5±1.5kg, a reduction in BMI of 1.0±0.8kg/m2, and a decrease in waist circumference of 3±2cm. It is concluded that the ketogenic diet may offer metabolic and reproductive benefits for overweight women with polycystic ovary syndrome. The improvements observed in metabolic parameters and menstrual regularity support the potential role of KD as a therapeutic intervention in PCOS management.

Comparing Effect of Sitagliptin versus Empagliflozin as Add on Therapy to Metformin in Patients with Type 2 Diabetes Mellitus

Background: Type 2 Diabetes Mellitus (T2DM) presents a substantial health challenge. Metformin is established as a standard treatment. This study evaluates sitagliptin, a dipeptidyl peptidase-4 inhibitor, and empagliflozin, a sodium-glucose cotransporter-2 inhibitor, as adjunct therapies to improve T2DM management. Objective: To compare effect of sitagliptin versus empagliflozin as add on therapy to metformin in patients with T2DM. Study Design: It was a prospective comparative study. Settings: This study was conducted at the Department of Medicine, DHQ Teaching Hospital, KMU Institute of Medical Sciences, Kohat Pakistan. Duration: 6 months period from March-September, 2023. Methods: A sample size of 100 cases was randomly assigned to either Group A or Group B. In conjunction with the standard metformin regimen (1000 mg twice daily), eligible patients were randomly assigned in a 1:1 ratio to receive either 50 mg of sitagliptin (Group A) or 12.5 mg of empagliflozin (group B) twice daily over 12 weeks. Study visits were scheduled at screening, weeks 0, and 12 of therapy, with no permitted dosage adjustments for the investigational drug. All the data was collected in a predesigned format and data analysis was done using SPSS 27.0. Results: Mean age of the patients in this study was 52.58±10.0 years in which 43.0% (n=43) participants were male while remaining 57% (n=57) were females. Both the groups were comparable with each other and did not possess any inherit difference between them with regard to all baseline characteristics (p-value &gt;0.05. After three months mean HbA1C in group B was significantly less than group A (8.00±0.13 vs. 7.42±0.08%; p-value=0.000). Mean change in HbA1c at three months from the values at presentation was significantly high in group B than group A (-0.70±0.25 vs. -1.33±0.17%; p-value=0.000). Comparison of mean weight between the groups shows significantly less mean weight in group B at three months than group A (64.14±4.25 vs. 61.84±4.89 kg; p-value=0.014). Mean change in weight at three months was significantly high in group B than group A. When mean change in HbA1C and mean reduction in weight in both the groups was stratified for age and gender, it produced same significance for all the stratifications (p-value=0.000). Conclusion: In conclusion, our study reveals that empagliflozin leads to superior glycemic control and greater weight reduction compared to sitagliptin as add on therapy to metformin in patients T2DM. These findings emphasize the potential benefits of individualized treatment strategies for optimized outcomes in T2DM management.

Therapeutic effectiveness of keratinized mucosa augmentation for functioning dental implants: A systematic review and meta-analysis.

This study aimed to provide the latest updates on the therapeutic effectiveness of keratinized mucosa (KM) augmentation using autogenous soft tissue grafts for dental implants retaining prostheses. A systematic search of electronic databases was conducted on autogenous soft tissue grafts to create and/or augment KM for functioning dental implants. Two investigators independently extracted data from the selected 11 clinical studies, including 290 participants, from the initially retrieved 573 publications. A lack of KM surrounding dental implants was associated with greater mucosal inflammation. A free gingival graft (FGG) was used to increase the KM width, and a connective tissue graft (CTG) was used to manage peri-implant mucosal recession (MR). The weighted mean gain in KM was 2.6 mm from the selected FGG studies, with a significant reduction in mucosal inflammation and no changes in crestal bone levels for up to 4 years. The weighted mean reduction in MR was 2 mm in selected CTG studies. A lack of KM negatively affects soft tissue health around dental implants. FGG was effective in increasing KM and reducing mucosal inflammation, whereas CTG was effective in decreasing MR.

Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity

The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown. To assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction. This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes. Participants (n = 783) enrolled in an open-label lead-in period received once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide for 36 weeks. At week 36, a total of 670 participants were randomized (1:1) to continue receiving tirzepatide (n = 335) or switch to placebo (n = 335) for 52 weeks. The primary end point was the mean percent change in weight from week 36 (randomization) to week 88. Key secondary end points included the proportion of participants at week 88 who maintained at least 80% of the weight loss during the lead-in period. Participants (n = 670; mean age, 48 years; 473 [71%] women; mean weight, 107.3 kg) who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was -5.5% with tirzepatide vs 14.0% with placebo (difference, -19.4% [95% CI, -21.2% to -17.7%]; P < .001). Overall, 300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period compared with 16.6% receiving placebo (P < .001). The overall mean weight reduction from week 0 to 88 was 25.3% for tirzepatide and 9.9% for placebo. The most common adverse events were mostly mild to moderate gastrointestinal events, which occurred more commonly with tirzepatide vs placebo. In participants with obesity or overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction. ClinicalTrials.gov Identifier: NCT04660643.

Impact of an Okinawa/Nordic based diet on endocrinological and periodontal conditions in individuals with type 2 diabetes. A randomized case–control study

ObjectivesTo assess if the results following intake of a diet using an Okinawan-based Nordic diet (OBND) over one month differs in endocrinological, periodontal clinical outcome, and serum cytokine levels compared to a standard hospital care diet in individuals with diabetes type 2 (T2D) (control group).BackgroundScientific evidence suggests that the use of diet for individuals with T2D may be beneficial.MethodsParticipating individuals with T2D were randomly assigned to a test (OBND) (n = 14), or control group (n = 16). Anthropometric data, blood glucose levels, HbA1c levels, lipids, serum inflammation markers (CRP, and a routine panel of 24 cytokines), blood pressure, gingival bleeding on probing (BOP), probing pocket depths (PPD), and clinical attachment levels (CAL) were studied.ResultsStatistical analyses of baseline study data failed to demonstrate study group differences. The mean weight reduction was greater in the OBND group (4.1 kg) versus the control group (1.3 kg) (p < 0.01). The reduction in BMI was 1.4 kg/m2 in OBND (p < 0.001) and 0.5 kg/m2 in the control group, respectively (p < 0.01). Diastolic and systolic blood pressure reductions were greater in the OBND group than in the control group (p < 0.01). Periodontal study parameters (BOP % scores) and (PPD values) decreased (p < 0.001) overall with no between group differences. The OBND resulted in reduction of serum levels of IFNγ, Eotaxin IL-9, IP10,IL17a, MCP-1,m and PDFBB compared to the control diet.ConclusionsA strict T2D- diet provides an association between reduction in serum HbA1c and BOP scores. Serum levels decreases in IFNγ, Eotaxin IL-9, IP-10, IL17a. MCP-1, and PDFBB were only found in the test group.