Racial and Ethnic Disparities in Financial Barriers Among Overweight and Obese Adults Eligible for Semaglutide in the United States.

Background Semaglutide holds the promise for weight loss and risk reduction. Less is known about racial and ethnic disparities in financial barriers among the semaglutide-eligible population. Methods and Results We conducted a cross-sectional analysis of adults aged 18 years or older using data from the National Health and Nutrition Examination Survey 2015 to 2020. We analyzed adults eligible for semaglutide based on Food and Drug Administration labeling and assessed financial barriers and social determinants of health among the eligible population overall and by race and ethnicity. A total of 13 711 adults were included in the final analysis. In 2015 to 2020, 51.1% (48.3%-53.2%) of US adults (≈43.3 million) met the Food and Drug Administration eligibility criteria for semaglutide. The percentage of adults eligible for semaglutide was highest among Black adults (56.6% [54.2%-59.1%]), followed by Hispanic adults (55.0% [52.8%-57.3%]). Among adults eligible for semaglutide, 11.9% (10.1%-13.6%) were uninsured, 13.3% (12.1%-14.5%) lacked a usual source of care, 33.6% (30.2%-36.9%) had low family income, and 38.9% (36.5%-41.3%) lacked higher education. Compared with White individuals, significantly larger proportions of Black and Hispanic individuals were uninsured, lacked a usual source of care, had low family income, or lacked higher education (P<0.001 for all). Conclusions Many Americans who were eligible for semaglutide were likely to be unable to afford the medication. Among the eligible population, a larger proportion of Black and Hispanic adults had financial barriers than other subgroups.

Once-Weekly Semaglutide for Weight Management: A Clinical Review.

Objective: To review the efficacy, safety, and role of the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide for chronic weight management. Data Sources: A literature search of PubMed/MEDLINE and Google Scholar was performed using the search terms: semaglutide 2.4, weight, and obesity. Ongoing studies of semaglutide were identified utilizing clinicaltrials.gov. Study Selection and Data Extraction: All English-language articles evaluating the efficacy and safety of semaglutide 2.4 mg for weight management in humans were included. Data Synthesis: Once-weekly injectable semaglutide 2.4 mg is indicated as an adjunct to a reduced-calorie diet and increased exercise for chronic weight management in adults with a body mass index (BMI) ≥30 kg/m2 or ≥27 kg/m2 with at least one weight-related comorbidity, such as hypertension, type 2 diabetes mellitus, or dyslipidemia. Semaglutide 2.4 mg has consistently demonstrated clinically significant weight loss across all phase 3 STEP (semaglutide treatment effect in people with obesity) trials, and long-term efficacy and safety have been confirmed for up to 2 years. Gastrointestinal side effects were the most frequently reported side effects, including nausea, vomiting, constipation, and diarrhea. Safety data for semaglutide 2.4 mg were consistent with that reported previously for the GLP-1 receptor agonist class. Conclusions: Semaglutide 2.4 mg is a highly efficacious agent for weight management, with a safety profile similar to that of other GLP-1 receptor agonists. It is a feasible option for chronic weight management, with data for up to 2 years. It is currently the only once-weekly weight loss medication, although cost may limit its utilization.

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management.

OBJECTIVE: To review the pharmacology, efficacy, and safety of high-dose once-weekly semaglutide for chronic weight management. DATA SOURCES: PubMed/MEDLINE and ClinicalTrials.gov were searched (inception to September 8, 2021) using keywords "semaglutide" and "obesity," "weight," "high dose," "high-dose," or "2.4." STUDY SELECTION AND DATA EXTRACTION: Clinical trials with published results were included. Publications studying the oral or <2.4 mg formulation of semaglutide were excluded. DATA SYNTHESIS: Four phase 3, multicenter, randomized, double-blind trials demonstrated efficacy of high-dose once-weekly semaglutide compared with placebo for weight loss. Study populations included patients with overweight or obesity (STEP 1, STEP 3, and STEP 4) or patients with diabetes and with overweight or obesity (STEP 2). Lifestyle interventions for diet and exercise were included for all participants. Weight loss from baseline was significant for all studies, and secondary outcomes demonstrated cardiometabolic improvements including waist circumference, systolic blood pressure, and lipid profiles. Gastrointestinal adverse effects were common, but the medication was otherwise well tolerated. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: High-dose semaglutide offers significant weight-lowering potential and favorable effects on cardiometabolic risk factors and glycemic indices. Clinicians and patients should consider the route and frequency of administration, adverse effect profile, and cost when choosing an antiobesity medication. The importance of concomitant lifestyle interventions should be emphasized. CONCLUSIONS: High-dose once-weekly semaglutide can significantly reduce weight, and although gastrointestinal adverse effects were common, it is generally well tolerated.

Exercise Fat Oxidation Is Positively Associated with Body Fatness in Men with Obesity: Defying the Metabolic Flexibility Paradigm.

Obesity is thought to be associated with a reduced capacity to increase fat oxidation in response to physical exercise; however, scientific evidence supporting this paradigm remains scarce. This study aimed to determine the interrelationship of different submaximal exercise metabolic flexibility (Metflex) markers and define its association with body fatness on subjects with obesity. Twenty-one male subjects with obesity performed a graded-intensity exercise protocol (Test 1) during which cardiorespiratory fitness (CRF), maximal fat oxidation (MFO) and its corresponding exercise intensity (FATmax) were recorded. A week afterward, each subject performed a 60-min walk (treadmill) at FATmax (Test 2), and the resulting fat oxidation area under the curve (TFO) and maximum respiratory exchange ratio (RERpeak) were recorded. Blood lactate (LAb) levels was measured during both exercise protocols. Linear regression analysis was used to study the interrelationship of exercise Metflex markers. Pearson's correlation was used to evaluate all possible linear relationships between Metflex and anthropometric measurement, controlling for CRF). The MFO explained 38% and 46% of RERpeak and TFO's associated variance (p < 0.01) while TFO and RERpeak were inversely related (R2 = 0.54, p < 0.01). Body fatness positively correlated with MFO (r = 0.64, p < 0.01) and TFO (r = 0.63, p < 0.01) but inversely related with RERpeak (r = -0.67, p < 0.01). This study shows that MFO and RERpeak are valid indicators of TFO during steady-state exercise at FATmax. The fat oxidation capacity is directly associated with body fatness in males with obesity.

Effects of Polyphenol-Rich Fruit Extracts on Diet-Induced Obesity in Rodents: Systematic Review and Meta-Analysis.

BACKGROUND: Obesity is a complex condition of high prevalence and cost to the public health system. Recent research has demonstrated the potential of natural products, such as polyphenol-rich fruit extracts, for use in the treatment of obesity. The goal of this systematic review and meta-analysis is to determine the metabolic effects of polyphenol-rich fruit extracts on diet-induced obesity (DIO) in rodents. METHODS: We searched MEDLINE, EMBASE, and Web of Science databases to identify preclinical studies that assessed polyphenol-rich fruit extracts compared to placebo on DIO in rodents in December 2018. Two researchers selected the studies, extracted the data, and assessed the quality of studies. Meta-analyses of standardized mean difference (SMD) of outcomes were calculated in Stata 11, and causes of heterogeneity were assessed by meta-regression. RESULTS: We included 14 studies in the systematic review and 13 studies with 21 matched groups in the metaanalysis. Polyphenol-rich fruit extracts reduced the total body weight gain (SMD = -1.48; confidence interval: - 1.95, -1.01), energy intake (SMD = -0.42; -0.67, -0.17), visceral adipose tissue (SMD = -0.96; -1.25, -0.66), triglycerides (SMD = -1.00; -1.39, -0.62), cholesterol (SMD = -1.18, -1.66, -0.69), LDL- c (SMD = -1.15; -1.65, - 0.65), fasting glucose (SMD = -1.05; -1.65, -0.46), and fasting insulin (SMD = -1.40; -1.80, -1.00) when compared to vehicle. CONCLUSION: Polyphenol-rich fruit extract had positive effects on weight gain, dyslipidaemia, insulin resistance at different doses, and fruit source in male mice.

Epidemiology of Obesity and Pharmacologic Treatment Options.

Prevalence of obesity and its related morbidity have increased to alarming levels in adults and children in the United States and globally. Weight loss results in improvement of much of the obesity-related morbidity. Lifestyle changes such as dietary modifications, increased physical activity, and behavioral therapy form the crux of weight management. However, many individuals need additional assistance (pharmacologic or surgical) to initiate or sustain weight loss. Pharmacologic therapy consists of a number of agents that work by decreasing appetite, gastric emptying, or nutrient absorption or by increasing satiety. Five classes of drug are currently approved for adults, including sympathomimetics (with and without an antiepileptic agent topiramate), gastrointestinal lipase inhibitors, serotonin agonists, glucagon-like peptide 1 agonists, and antidepressant/opioid antagonist combination. Pharmacologic options for children with obesity are minimal (lipase inhibitor orlistat is the only approved medication for children aged >12 years); however, all adult medications are approved by the Food and Drug Administration for children aged >16 years old. While side effect profiles of these medications are far superior to older medications, their use is limited by lack of long-term cardiovascular safety data, costs of medications and variable insurance coverages, and the need for continued usage for sustainable benefits. Weight loss medications may induce complacence, on part of both the patient and the provider, regarding lifestyle modifications, without which the drug therapy is almost certain to be of minimal benefit. Several novel drugs are in the pipeline targeting brown fat, energy expenditure, appetite suppression, and satiety.

Small lipidated anti-obesity compounds derived from neuromedin U.

A small library of truncated/lipid-conjugated neuromedin U (NmU) analogs was synthesized and tested in vitro using an intracellular calcium signaling assay. The selected, most active analogs were then tested in vivo, and showed potent anorexigenic effects in a diet-induced obese (DIO) mouse model. The most promising compound, NM4-C16 was effective in a once-weekly-dose regimen. Collectively, our findings suggest that short, lipidated analogs of NmU are suitable leads for the development of novel anti-obesity therapeutics.

Drug treatment of obesity: current status and future prospects.

Obesity is a growing epidemic and a major contributor to the global burden of disease. Obesity strains the healthcare systems and has profound economic and psychosocial consequences. Historically, pharmacotherapy for obesity has witnessed the rise and fall of several promising drug candidates that had to be eventually withdrawn due to unacceptable safety concerns. Currently four drugs are approved for chronic weight management in obese adults: orlistat, lorcaserin, phentermine/topiramate extended release and naltrexone/bupropion extended release. While lorcaserin and phentermine/topiramate were approved by US Food and Drug Administration (FDA) in 2012, after a gap of 13 years following the licensing of orlistat, naltrexone/bupropion has been recently approved in 2014. This review provides a brief overview of these current therapeutic interventions available for management of obesity along with the evidence of their safety and efficacy. Additionally, several novel monotherapies as well as combination products are undergoing evaluation in various stages of clinical development. These therapies if proven successful will strengthen the existing armamentarium of antiobesity drugs and will be critical to combat the global public health crisis of obesity and its associated co-morbidities.

Thermogenic brown and beige/brite adipogenesis in humans.

Evidence from rodents established an important role of brown adipose tissue (BAT) in energy expenditure. Moreover, to sustain thermogenesis, BAT has been shown to be a powerful sink for draining and oxidation of glucose and triglycerides from blood. The potential of BAT activity in protection against obesity and metabolic syndrome is recognized. Recently, an unexpected presence and activity of BAT has been found in adult humans. Here we review the most recent research in this field and, specifically, how new findings apply to humans. Moreover, we seek to clarify the underlying biological processes occurring beyond the burst of new nomenclature in the field. The cell type responsible for thermogenesis, the brown adipocyte, arises from complex developmental processes. In addition to 'classical' brown adipocytes, present in developmentally programmed BAT depots, there are brown adipocytes, named 'brite' (from 'brown-in-white') or 'beige', which appear in response to thermogenic stimuli in white fat due to the so-called 'browning' process. Beige/brite cells appear to be important components of BAT depots in adult humans. In addition to the known control of BAT activity by the sympathetic nervous system, metabolic and hormonal signals originating in muscle or liver (e.g. irisin, FGF21) are recognized as activators of BAT and beige/brite adipocytes.

Effects of weight loss on renal function in obese CKD patients: a systematic review.

Obesity is an independent risk factor for the development and progression of chronic kidney disease (CKD). We conducted a systematic review to assess the benefits of intentional weight loss in obese subjects with altered glomerular filtration rate (GFR), proteinuria or albuminuria. MEDLINE, EMBASE and CENTRAL databases were searched for articles reporting longitudinal data on the effect of weight loss on renal parameters in obese patients with altered kidney function. Thirty-one (2013 subjects) were included. In the 13 studies where weight loss was achieved by bariatric surgery, body mass index (BMI) significantly decreased in all studies; GFR decreased in six studies on hyperfiltration patients and increased in one study on patients with CKD Stage 3-4. Albuminuria decreased in six studies and proteinuria decreased in five studies. In six studies, weight loss was achieved by antiobesity agents: BMI decreased in all studies; GFR decreased in four studies and albuminuria in three. Eleven studies analysed the effects of diet, alone or in combination with lifestyle modifications. A significant decrease in BMI was reported in all studies; GFR increased in two studies, remained stable in four studies and decreased in two studies on hyperfiltration patients. Albuminuria decreased in six studies and remained stable in one study. Proteinuria decreased in five studies. In obese patients with altered renal function, weight loss, particularly if achieved by surgical interventions, improves proteinuria, albuminuria and normalizes GFR. Larger, long-term studies are needed to analyse the durability of this improvement and the effects on renal outcomes, such as CKD progression and the development of ESKD.

Zonisamide for weight loss in adolescents.

Obesity in children and adolescents is a growing epidemic in the United States, and physicians are increasingly looking for safe and effective treatments. In recent years, pharmacologic treatment has been considered for severe and refractory cases of adolescent obesity. We present a case of an obese adolescent who presented to an inpatient psychiatric unit with a body mass index (BMI) of 37.8 (>98th percentile for age). He was started on zonisamide for the purposes of weight loss, and a steady decrease in weight and BMI was noted through 4 months of outpatient follow-up. During this time, the patient's weight decreased from 126.8 kg to 106.2 kg, a 20.6-kg loss, representing a 16.25% reduction in weight. His most recent BMI decreased to 31.7 (96th percentile for age). We discuss the potential use of zonisamide for weight loss in adolescents, considering the potential risks and benefits.

Evaluation of efficacy and safety of orlistat in obese patients.

CONTEXT: Rapidly rising prevalence of obesity is alarming. Obesity predisposes to co-morbidities like hypertension, type 2 diabetes mellitus, dyslipidemias, thus substantially rising healthcare expenditure. Lifestyle modifications alone have very limited success, necessitating the addition of pharmacotherapy to it. OBJECTIVE: Present study was carried out to evaluate the efficacy and safety of orlistat in obese patients. MATERIALS AND METHODS: Eighty obese (BMI>30) patients according to inclusion and exclusion criteria were randomized into either of the two groups. Group 1 received orlistat 120 mg three times a day and group 2 received placebo three times a day. Weight, waist circumference, BMI, total cholesterol, triglycerides, HDL, LDL were measured at baseline and then at 8(th), 16(th) and 24(th) week. ADR reported by patients were recorded. For safety evaluation various hematological and biochemical parameters were assessed. Z test was used for analysis of data. RESULTS: Compared to placebo, orlistat caused significant reduction (P<0.05) in weight (4.65 kg vs 2.5 kg; orlistat vs placebo, respectively), BMI (1.91 kg/m(2) vs 0.64 kg/m(2)) and waist circumference (4.84 cm vs 2 cm), cholesterol (10.68 mg vs 6.18 mg) and LDL level (5.87 mg vs 2.33 mg). In the orlistat group, the GI side effects like loose stools, oily stools/spotting, abdominal pain and fecal urgency were observed. CONCLUSION: Orlistat is an effective and well-tolerated antiobesity drug, which can be employed as an adjunct to therapeutic lifestyle changes to achieve and maintain optimal weight.

Dyslipidemia induced by drugs used for the prevention and treatment of vascular diseases.

Dyslipidemia is a major vascular risk factor. Interestingly, several agents used for the prevention and treatment of vascular diseases have an adverse effect on the lipid profile. In addition, agents belonging to the same class (e.g. beta blockers) can have significantly different actions on lipid levels. We summarize the effects of drugs used for the prevention and treatment of vascular diseases on the lipid profile. These effects should be considered when selecting a specific agent, particularly in high-risk patients.