Sex, race, and BMI in clinical trials of medications for obesity over the past three decades: a systematic review.

Medications for obesity have been studied in various populations over the past three decades. We aimed to quantify the baseline demographic characteristics of BMI, sex, age, and race in randomised clinical trials (RCTs) across three decades to establish whether the population studied is representative of the global population affected by the disease. Clinical trials of 12 medications for obesity (ie, orlistat, naltrexone-bupropion, topiramate-phentermine, liraglutide, semaglutide, lorcaserin, sibutramine, rimonabant, taranabant, tirzepatide, retatrutide, and orforglipron) published from Jan 20, 1999, to Nov 12, 2023, were assessed through a systematic review for methodological quality and baseline demographic characteristics. 246 RCTs were included, involving 139 566 participants with or without type 2 diabetes. Most trials over-recruited White, female participants aged 40 years or older with class 1 (30·0-34·9 kg/m2) and class 2 (35·0-39·9 kg/m2) obesity; older participants, those with class 3 (≥40·0 kg/m2) obesity, non-White participants, and male participants were under-recruited. Our systematic review suggests that future trials need to recruit traditionally under-represented populations to allow for accurate measures of efficacy of medications for obesity, enabling more informed decisions by clinicians. It is also hoped that these data will help to refine trial recruitment strategies to ensure that future studies are relevant to the population affected by obesity.

Perceived Benefits of Bariatric Surgery: Patient Perspectives.

BACKGROUND: Obesity is a chronic and complex disease characterized by the excessive accumulation of adipose tissue, which has detrimental effects on health. Evaluating the changes in quality of life (QoL) after bariatric surgery complements the medical benefits which are documented by healthcare professionals. PURPOSE: To study the perceived health benefits 1 year after substantial weight loss induced by bariatric surgery. METHODS: This pilot study evaluated patients 1 year after bariatric surgery using 13 questions related to the health domains of the KOSS: airway, body mass, cardiovascular risk, diabetes, economic impact, functional, gonadal impact, health status perceived, image, junction of the gastro-esophagus, kidney, liver, and medication. In addition, the patients were asked to score the most significant benefit as "1," while the least beneficial benefit was scored as "13." RESULTS: One hundred fourteen consecutive patients were evaluated (men = 37 and women = 77). The responses were divided into functional, metabolic, and mental/social benefits. Patients ranked the functional question, "I became more active, and I can do more things" as the most important (average score of 3.7 ± 0.2), followed by a question related to metabolic status: "I am less worried about my risk of heart disease" (4.5 ± 0.3), and then a social/mental question, "My clothes fit better" (5.4 ± 0.3). The three least valuable benefits for the cohort were sexual life improvements (8.9 ± 0.3), heartburn improvements (9.0 ± 0.3), and urinary incontinence improvements (9.8 ± 0.3). CONCLUSIONS: Our observational pilot study demonstrated that patients value functional benefits after substantial weight loss the most, but that metabolic benefits and social/mental health benefits are also considered important.

Weight loss response in patients with obesity treated with injectable semaglutide in a real-world setting.

BACKGROUND: Obesity is defined as excess adipose tissue causing a deterioration in health, but diagnosing the causes and deciding on treatment can be challenging. Several randomized controlled clinical trials (RCT) have demonstrated the effectiveness of semaglutide as a treatment for obesity. This study investigated the clinical response to semaglutide as a weight loss treatment in a real-world setting. METHODS: This observational study investigated the response to injectable semaglutide in the first 3 months during the dose titration phase up to 1 mg. Weight loss after 6 months was also evaluated. The data were collected from the electronic medical records (EMR) from outpatient clinics between July 2021 to March 2023. All participants were older than 18 years, with no history of bariatric surgery within 1 year, and had a least one prescription of injectable semaglutide. The primary outcome was weight change at 3 months. Weight loss in those patients who attended at 6 months was a secondary outcome. RESULTS: A total of 350 patients were included in the study. The vast majority (80.3%) were female. 287 patients (82%) completed 3 months on injectable semaglutide and lost 6.6 ± 3.8% bodyweight. 224 patients (64%) completed 6 months on semaglutide and lost 12 ± 6.1% bodyweight. 188 (65.5%) of patients who completed 3-month follow-up lost ≥5% weight, 39 (13.5%) patients lost ≥10% weight, and 7 (2.4%) patients lost ≥15% weight. While for those patients who completed the 2nd visit (n = 224), 201 (89.7%) lost ≥5% weight, 135 (60.3%) lost ≥10% weight, and 54 (24.1%) lost ≥ 15% body weight. CONCLUSION: Injectable semaglutide in a real-world setting resulted in similar weight loss and had a similar side effect profile as was observed in randomized controlled trials.

Obesity Characteristics Are Poor Predictors of Genetic Mutations Associated with Obesity.

BACKGROUND: The genetic contribution to obesity is substantial and may underpin the altered pathophysiology. One such pathway involves melanocortin signaling in the hypothalamus. Genetic variants can cause dysregulation in the central melanocortin pathway that can result in early onset of hyperphagia and obesity. Clinically identifying patients who are at risk of known genetic mutations is challenging. The main purpose of this study was to identify associations between the clinico-demographical characteristics and the presence of a genetic mutation associated with obesity. METHODS: We tested samples from 238 adult patients with class III obesity between October 2021 to February 2023 using next-generation sequencing (NGS) (Illumina, NovaSeq 6000 Sequencing System). The results were classified as "no variant identified" or "variant identified". RESULTS: 107 patients (45%) had one or more gene mutation in the leptin-melanocortin pathway. All variants were heterozygous. The patients with a gene mutation had a BMI of 48.4 ± 0.8 kg/m2 (mean ± SEM), and those without a gene mutation had a BMI of 49.4 ± 0.7 kg/m2 (p = 0.4). The mean age of onset of obesity in patients with a gene mutation was 13.9 ± 1.3 years and for those without gene mutations was 11.5 ± 0.9 years (p = 0.1). The incidence of hyperphagia as a child was also not predictive (p = 0.4). CONCLUSIONS: Gene mutations associated with obesity in patients with a BMI > 40 kg/m2 are common. However, a patient's BMI, age of onset of obesity, or age of onset of hyperphagia did not help to differentiate which patients may be more likely to have genetic mutations associated with obesity.

Weight loss to disrupt type 2 diabetes.

Obesity is now recognised as a disease associated with significant morbidity and mortality. One of the most common metabolic complications of obesity is type 2 diabetes, because the two disease share similar pathophysiology. Weight loss is known to ameliorate the metabolic abnormalities underlying type 2 diabetes and improve glycemic control. A 15% or greater total body weight loss (TBWL) in patients with type 2 diabetes will have a disease-modifying effect, a result that is incomparable with other hypoglycemic-lowering interventions. Moreover, in patients with diabetes and obesity, weight loss exerts benefits beyond glycemic control and improves cardiometabolic disease risk factors and well-being. We review evidence supporting the role of intentional weight loss in managing type 2 diabetes. We suggest that many people with type 2 diabetes would benefit from an additional weight-based approach to managing their diabetes. Therefore, we proposed a weight-based treatment goal for patients with type 2 diabetes and obesity.