Project description:ObjectiveLittle is known about the predictors of response to obesity interventions.MethodsIn 450 participants with obesity, body composition, resting energy expenditure, satiety, satiation, eating behavior, affect, and physical activity were measured by validated studies and questionnaires. These variables were used to classify obesity phenotypes. Subsequently, in a 12-month, pragmatic, real-world trial performed in a weight management center, 312 patients were randomly assigned to phenotype-guided treatment or non-phenotype-guided treatment with antiobesity medications: phentermine, phentermine/topiramate, bupropion/naltrexone, lorcaserin, and liraglutide. The primary outcome was weight loss at 12 months.ResultsFour phenotypes of obesity were identified in 383 of 450 participants (85%): hungry brain (abnormal satiation), emotional hunger (hedonic eating), hungry gut (abnormal satiety), and slow burn (decreased metabolic rate). In 15% of participants, no phenotype was identified. Two or more phenotypes were identified in 27% of patients. In the pragmatic clinical trial, the phenotype-guided approach was associated with 1.75-fold greater weight loss after 12 months with mean weight loss of 15.9% compared with 9.0% in the non-phenotype-guided group (difference -6.9% [95% CI -9.4% to -4.5%], P < 0.001), and the proportion of patients who lost >10% at 12 months was 79% in the phenotype-guided group compared with 34% with non-phenotype-guided treatment group.ConclusionsBiological and behavioral phenotypes elucidate human obesity heterogeneity and can be targeted pharmacologically to enhance weight loss.
Project description:ImportanceThe 2023 American College of Rheumatology and American Association of Hip and Knee Surgeons Clinical Practice Guideline concluded that obesity alone should not delay joint replacement. Therefore, a substantially increased utilization of joint replacement among patients with obesity could be expected. However, patients with obesity are at increased risk of revision, posing unique challenges as the surgery is complex and costly, and it remains unknown whether postoperative weight loss could decrease the risk of revision.ObjectiveTo examine the association of the proportion of postoperative weight loss following antiobesity medication use with the risk of revision among patients with obesity undergoing hip or knee replacement.Design, setting, and participantsUsing a target trial emulation, a causal inference framework, this retrospective cohort study investigated patients with obesity who underwent hip or knee replacement. Data were from the IQVIA Medical Research Database (2000-2023). Statistical analysis was performed from October 2023 to June 2024.Main outcomes and measuresEmulated analyses of a hypothetical target trial were assessed for the association of small-to-moderate (2%-10%) or large (≥10%) weight loss after initiating antiobesity medications (orlistat, sibutramine, glucagon-like peptide-1 receptor agonists, and rimonabant) within 1 year with the risk of 5-year and 10-year revision after initiation of antiobesity medications.ResultsAmong 3691 qualified participants (mean [SD] age, 64.7 [9.3] years; 2322 [62.9%] women), the 5-year risks of revision were 5.6%, 4.4%, and 3.7% for weight gain or stable, small-to-moderate weight loss, and large weight loss groups, respectively. Compared with the weight gain or stable group, the hazard ratios (HRs) were 0.75 (95% CI, 0.55-1.04) for the small-to-moderate weight loss group and 0.57 (95% CI, 0.36-0.91) for the large weight loss group. Similar results were observed when the analyses were performed separately for hip or knee replacement. The HRs for revision were 0.55 (95% CI, 0.32-0.93) for small-to-moderate weight loss and 0.49 (95% CI, 0.25-0.97) for large weight loss groups compared with the weight gain or stable group in patients undergoing knee replacement; the corresponding HRs for revision were 0.82 (95% CI, 0.54-1.25) and 0.53 (95% CI, 0.30-0.93) in patients undergoing hip replacement. Consistent findings were obtained regarding the association of weight loss with the 10-year risks after initiating antiobesity medications.Conclusions and relevanceIn this cohort study using a target trial emulation, a higher proportion of weight loss after initiating antiobesity medications within 1 year was associated with a lower risk of 5-year and 10-year revision among patients with obesity undergoing joint replacement. These results suggest that antiobesity medication use, with relatively safe and sustainable weight loss, may be an effective strategy for improving implant survivorship of hip and knee replacements in the obese population.
Project description:Obesity is a chronic, multifactorial disease associated with a large number of comorbidities. The clinical management of obesity involves a stepwise integrated approach, beginning with behavioral and lifestyle modification, followed by antiobesity medications, endobariatric procedures, and bariatric surgery. Weight gain and subsequent obesity are common side effects of medications, such as prednisone or antipsychotics. In this era of precision medicine, it is essential to identify patients at the highest risk of weight gain as a result of medication use. Pharmacogenomics could play an important role in obesity management by optimizing use of antiobesity medications as well as minimizing adverse weight gain. This review aims to provide a comprehensive analysis of the current literature on the role of pharmacogenomics in obesity and medication-induced weight gain. In summary, there are more robust studies of medication associated with weight gain and pharmacogenomics, and more studies are needed to understand the role of pharmacogenomics in antiobesity medications.
Project description:Purpose of reviewTo highlight the added benefits of approved and upcoming, centrally-acting, anti-obesity drugs, focusing not only on the most common metabolic and cardiovascular effects but also on their less explored clinical benefits and drawbacks, in order to provide clinicians with a tool for more comprehensive, pharmacological management of obesity.Recent findingsObesity is increasingly prevalent worldwide and has become a challenge for healthcare systems and societies. Reduced life expectancy and cardiometabolic complications are some of the consequences of this complex disease. Recent insights into the pathophysiology of obesity have led to the development of several promising pharmacologic targets, so that even more effective drugs are on the horizon. The perspective of having a wider range of treatments increases the chance to personalize therapy. This primarily has the potential to take advantage of the long-term use of anti-obesity medication for safe, effective and sustainable weight loss, and to concomitantly address obesity complications/comorbidities when already established. The evolving scenario of the availability of anti-obesity drugs and the increasing knowledge of their added effects on obesity complications will allow clinicians to move into a new era of precision medicine.
Project description:BackgroundVirtually-delivered obesity care has the potential to increase access to weight loss interventions at scale. While there is ample literature assessing various weight loss interventions, studies specifically demonstrating outcomes of commercial programs offering antiobesity medications in virtual care settings are lacking.MethodsThis retrospective cohort study assessed the weight loss outcomes of 66,094 participants in a virtual weight care program that prescribes antiobesity medications alongside a digital behavior change program. Outcomes included the primary endpoint of percent weight loss at 12 months, as well as absolute change in body weight, change in body mass index (BMI), categorical weight loss at three, six, and 12 months, and stratifications by program engagement and medication type (first vs. second generation antiobesity medications).ResultsAt program enrollment, members were on average 42.6 years old and 91.5% female, with a BMI of 36.0 kg/m2. At 12 months, the mean percent weight loss was 8.0%, with weight loss increasing over time from 2.9 kg (SD = 3.7, Cohen's d = 0.8) at 3 months, to 5.8 kg (SD = 6.1, Cohen's d = 0.9) at 6 months, to 8.0 kg (SD = 8.7, Cohen's d = 0.9) at 12 months (p < 0.001 for all time points). At 12 months, 64.2% had achieved ≥ 5% weight loss. Weight loss outcomes increased with program engagement. At 12 months, those engaging at least once weekly lost 10.0% of body weight, while those logging weight at least weekly lost 12.0%.ConclusionThis study provides real-world evidence that users of a virtual commercial weight care clinic who were prescribed antiobesity medications achieved clinically significant weight loss at six and 12 months. These findings support the value of virtual platforms in efficiently scaling access to high-quality weight care.
Project description:BackgroundThe prevalence of obesity and related diseases has increased enormously in the last few decades, becoming a very important medical and social issue. Because of the increasing number of people who need weight loss therapies and the high costs associated with these, the search for reliable predictors of success for weight loss and weight maintenance treatments has become a priority.ObjectiveA literature review was undertaken to identify possible predictors of outcome of weight loss and weight maintenance in patients treated with antiobesity drugs.ResultsFor the majority of variables, published data are not sufficient to define their role on final outcomes. Among all considered factors, only early response to treatment appeared to be a reliable positive predictor, and diabetes a negative predictor of weight loss and maintenance.ConclusionTo date, no definitive results have been obtained. Due to the great benefits of reliable predictors of outcome associated to currently available antiobesity drugs and those under development, identifying these predictors has to be supported and encouraged.
Project description:The hypothesis tested in the present study was The effect fo weight loss by dietary intervention with very low calorie diet on colorectal inflammatory genes and genepathways. The study results have shown that a 10% weight loss in obese women down-regulated inflammatory and cancer gene pathways. In addition there was downregulation of transcription factors known to play an important role in colorectal cancer. Total RNA obtained from colorectal mucosal biopsy samples
Project description:IntroductionAlthough people with chronic kidney disease (CKD) and obesity have important motivations to lose weight, weight loss is also associated with health risks. We examined whether patterns of change in systolic blood pressure (SBP), serum albumin level, and fat-free mass (FFM) can help to differentiate between healthy and high-risk weight loss in this population.MethodsUsing data from the Chronic Renal Insufficiency Cohort Study (CRIC), we estimated a joint multivariate latent class model with 6 classes to identify distinct trajectories of body mass index (BMI), albumin, and SBP among participants with obesity (BMI ≥30 kg/m2 at baseline), accounting for informative missingness from death. In a secondary analysis, we fit a 6-class model with BMI and FFM.ResultsAmong 2831 participants (median baseline BMI 35.6, interquartile range [IQR] 32.4-40.0 kg/m2), median follow-up was 6.8 (IQR 4.8-12.9) years, median age was 61 (IQR 54-67) years, 53% were male, 50% were non-Hispanic Black, and 82% were trying to control or lose weight at baseline. Latent classes were associated with mortality risk (5-year cumulative incidence of mortality 6.8% and 1.5% in class 6 and 3, respectively). Class 6 had the highest mortality rate and was characterized by early, steep BMI loss, early serum albumin decline, and late SBP increase. In the secondary analysis, a class characterized by steep BMI and FFM loss was associated with the highest death risk.ConclusionsAmong adults with CKD and obesity, BMI loss with concomitant serum albumin or FFM loss was associated with a high risk of death.