Objective:
To formulate clinical practice guidelines for the pharmacological management of obesity.
Participants:
An Endocrine Society-appointed Task Force of experts, a methodologist, and a medical ...writer. This guideline was co-sponsored by the European Society of Endocrinology and The Obesity Society.
Evidence:
This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe the strength of recommendations and the quality of evidence.
Consensus Process:
One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the European Society of Endocrinology, and The Obesity Society reviewed and commented on preliminary drafts of these guidelines. Two systematic reviews were conducted to summarize some of the supporting evidence.
Conclusions:
Weight loss is a pathway to health improvement for patients with obesity-associated risk factors and comorbidities. Medications approved for chronic weight management can be useful adjuncts to lifestyle change for patients who have been unsuccessful with diet and exercise alone. Many medications commonly prescribed for diabetes, depression, and other chronic diseases have weight effects, either to promote weight gain or produce weight loss. Knowledgeable prescribing of medications, choosing whenever possible those with favorable weight profiles, can aid in the prevention and management of obesity and thus improve health.
Update on Obesity Bessesen, Daniel H
The journal of clinical endocrinology and metabolism,
2008-June, Letnik:
93, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Endocrinologists have unique skills in evaluating and caring for patients with metabolic diseases. As such, they have a special role to play within the organizations in which they work as leaders in ...the approach to managing obese patients. Recent epidemiological data demonstrate that the prevalence of obesity is beginning to plateau. However, the rate of severe obesity in adults and the prevalence of overweight among children continue to grow, suggesting that in the future there will be an increasing burden of obesity-related illnesses. A number of recent studies have identified a number of novel mechanisms that predispose to obesity including several newly identified genes, the role of intestinal microflora, and even social networks. The selection of treatment for obese patients remains a complex issue. Recent studies demonstrate that a range of dietary approaches including the Atkins diet can provide modest weight loss, although the key feature appears to be adherence in the dietary strategy. High levels of physical activity appear to be necessary to maintain a reduced state, although modest increases in activity improve fitness. Although the new understanding of biology of weight regulation has provided a wide range of potential drug targets, available pharmacotherapy options remain limited although a number of potential targets show promise. Recent data provides the most enthusiasm for surgical treatment of obesity. Several recent studies demonstrate a reduction in mortality and dramatic benefits in diabetes in obese patients treated surgically. Questions remain as to the best surgical approach and the cost effectiveness. Research advances in obesity continue to move at a rapid pace and raise hopes for more effective management strategies in the future.
Metabolic flexibility is defined as the ability to adapt substrate oxidation rates in response to changes in fuel availability. The inability to switch between the oxidation of lipid and carbohydrate ...appears to be an important feature of chronic disorders such as obesity and type 2 diabetes. Laboratory assessment of metabolic flexibility has traditionally involved measurement of the respiratory quotient (RQ) by indirect calorimetry during the fasted to fed transition (e.g. mixed meal challenge) or during a hyperinsulinaemic–euglycaemic clamp. Under these controlled experimental conditions, ‘metabolic inflexibility’ is characterized by lower fasting fat oxidation (higher fasting RQ) and/or an impaired ability to oxidize carbohydrate during feeding or insulin‐stimulated conditions (lower postprandial or clamp RQ). This experimental paradigm has provided fundamental information regarding the role of substrate oxidation in the development of obesity and insulin resistance. However, the key determinants of metabolic flexibility among relevant clinical populations remain unclear. Herein, we propose that habitual physical activity levels are a primary determinant of metabolic flexibility. We present evidence demonstrating that high levels of physical activity predict metabolic flexibility, while physical inactivity and sedentary behaviours trigger a state of metabolic ‘inflexibility’, even among individuals who meet physical activity recommendations. Furthermore, we describe alternative experimental approaches to studying the concept of metabolic flexibility across a range of activity and inactivity. Finally, we address the promising use of strategies that aim to reduce sedentary behaviours as therapy to improve metabolic flexibility and reduce weight gain risk.
Sedentary behaviour is a key determinant of metabolic inflexibility. In our view, metabolic flexibility can be assessed by examining the allostatic relationship between a regulator (e.g. insulin, catecholamines, brown adipose tissue sympathetic nervous system) and an effector (respiratory quotient, lipolysis, or proton leak brown adipose tissue mitochondrial membrane) in response to a stressor (e.g. meal consumption, exercise, or cold exposure). Stressors can be of physiological or environmental origin. In general, a physically inactive individual responds to a stressor with either an increase in the amplitude/mean concentration of the regulator or a decrease in the amplitude/mean concentration of the effector.
Intermuscular adipose tissue (IMAT) is negatively related to insulin sensitivity, but a causal role of IMAT in the development of insulin resistance is unknown. IMAT was sampled in humans to test for ...the ability to induce insulin resistance in vitro and characterize gene expression to uncover how IMAT may promote skeletal muscle insulin resistance. Human primary muscle cells were incubated with conditioned media from IMAT, visceral (VAT), or subcutaneous adipose tissue (SAT) to evaluate changes in insulin sensitivity. RNAseq analysis was performed on IMAT with gene expression compared with skeletal muscle and SAT, and relationships to insulin sensitivity were determined in men and women spanning a wide range of insulin sensitivity measured by hyperinsulinemic-euglycemic clamp. Conditioned media from IMAT and VAT decreased insulin sensitivity similarly compared with SAT. Multidimensional scaling analysis revealed distinct gene expression patterns in IMAT compared with SAT and muscle. Pathway analysis revealed that IMAT expression of genes in insulin signaling, oxidative phosphorylation, and peroxisomal metabolism related positively to donor insulin sensitivity, whereas expression of macrophage markers, inflammatory cytokines, and secreted extracellular matrix proteins were negatively related to insulin sensitivity. Perilipin 5 gene expression suggested greater IMAT lipolysis in insulin-resistant individuals. Combined, these data show that factors secreted from IMAT modulate muscle insulin sensitivity, possibly via secretion of inflammatory cytokines and extracellular matrix proteins, and by increasing local FFA concentration in humans. These data suggest IMAT may be an important regulator of skeletal muscle insulin sensitivity and could be a novel therapeutic target for skeletal muscle insulin resistance.
Summary
The role of physical activity (PA) in the regulation of body weight is still a major topic of debate. This may be because studies have essentially focused on the effects of moderate/vigorous ...PA (MVPA) on body weight while overlooking the other components of PA, namely, light‐intensity PA (LPA, daily life activities) and sedentary behaviors (SB, too much sitting). In this review, we will (i) describe the history of changes in PA behaviors that occurred with modernization; (ii) review data from cross‐sectional and longitudinal studies that examined the associations between PA, SB, and measures of obesity; (iii) review interventional studies that investigated the effects of changes in PA and SB on body weight and adiposity; and (iv) discuss experimental studies that addressed potential biological mechanisms underlying the effects of PA and SB on weight regulation. Overall recent findings support the importance of considering all components of PA to better understand the regulation of energy balance and suggest an important role for LPA and SB in addition to MVPA on body weight regulation. Longitudinal large‐scale rigorous studies are needed to advance our knowledge of the role of PA/SB in combating the obesity epidemic.
Physical inactivity, i.e. not reaching the recommended level of physical activity (PA), and sedentary behaviours (SB), i.e. sitting time, have been associated with increased risk for common metabolic ...diseases. Recent epidemiological data suggest that high volumes of SB are detrimental to metabolic health, even in the presence of regular exercise, i.e. moderate/vigorous PA. This suggests that the health effects of SB are independent from those of exercise. However, experimentally testing this hypothesis is complicated because of the difficulty in disassociating SB from PA. Bedrest studies, a traditional space science model, can offer new insights. In some bedrest studies, an exercise training protocol has been used to counteract the harmful effects of inactivity. While bedrest induces an inactive and sedentary state, exercise with bedrest represents a unique model of sedentary yet physically active people. Here, we review bedrest studies with and without exercise training. Although exercise training prevents the loss of muscle mass and function, even large volumes of exercise are not sufficient to fully counteract the negative metabolic adaptations triggered by inactivity. This observation supports the existence of independent adverse health effects of SB, but also the potential benefits of non‐exercise activity, i.e. daily living light PA. We gathered available data to examine the complex relationships between exercise, non‐exercise activity, SB and health outcomes. Given the large amount of SB in modern societies, the sole promotion of exercise, i.e. moderate/vigorous PA may be insufficient, and promotion of light PA may be a complimentary approach to improve health.
figure legend Although the exact physiological mechanisms remain unclear, sedentariness has been shown to negatively affect metabolic health and the main organs involved in its regulation. The 2020 World Health Organization (Bull et al. 2020) guidelines on physical activity recommend practicing a weekly volume of 150–300 min of moderate intensity or 75–150 min of vigorous intensity or an equivalent combination of moderate/vigorous physical activity (MVPA) to limit the appearance of certain maladaptations. Recently, some large‐scale studies have revealed the importance of light physical activity (LPA) to prevent the effects of sedentary lifestyles. Since then, limiting periods of sedentary time have become part of the recommendations for the first time, raising the question of how to reduce periods of sedentary living. This review aims to highlight the potential role of LPA in effectively reducing sitting time and preventing its associated harmful health effects. Intervention studies specifically targeting LPA and sedentary behaviour, in addition to MVPA, are necessary to develop specific recommendations and limit the risk of developing metabolic diseases.
The regulation of energy intake is a complex process involving the integration of homeostatic signals and both internal and external sensory inputs. The objective of this study was to examine the ...effects of short-term overfeeding on the neuronal response to food-related visual stimuli in individuals prone and resistant to weight gain.
22 thin and 19 reduced-obese (RO) individuals were studied. Functional magnetic resonance imaging (fMRI) was performed in the fasted state after two days of eucaloric energy intake and after two days of 30% overfeeding in a counterbalanced design. fMRI was performed while subjects viewed images of foods of high hedonic value and neutral non-food objects. In the eucaloric state, food as compared to non-food images elicited significantly greater activation of insula and inferior visual cortex in thin as compared to RO individuals. Two days of overfeeding led to significant attenuation of not only insula and visual cortex responses but also of hypothalamus response in thin as compared to RO individuals.
These findings emphasize the important role of food-related visual cues in ingestive behavior and suggest that there are important phenotypic differences in the interactions between external visual sensory inputs, energy balance status, and brain regions involved in the regulation of energy intake. Furthermore, alterations in the neuronal response to food cues may relate to the propensity to gain weight.
Recent publicity around the use of new antiobesity medications (AOMs) has focused the attention of patients and healthcare providers on the role of pharmacotherapy in the treatment of obesity. Newer ...drug treatments have shown greater efficacy and safety compared with older drug treatments, yet access to these drug treatments is limited by providers' discomfort in prescribing, bias, and stigma around obesity, as well as by the lack of insurance coverage. Now more than ever, healthcare providers must be able to discuss the risks and benefits of the full range of antiobesity medications available to patients, and to incorporate both guideline based advice and emerging real world clinical evidence into daily clinical practice. The tremendous variability in response to antiobesity medications means that clinicians need to use a flexible approach that takes advantage of specific features of the antiobesity medication selected to provide the best option for individual patients. Future research is needed on how best to use available drug treatments in real world practice settings, the potential role of combination therapies, and the cost effectiveness of antiobesity medications. Several new drug treatments are being evaluated in ongoing clinical trials, suggesting that the future for pharmacotherapy of obesity is bright.
Objective
The aim of this study was to examine the prescribing patterns and use of antiobesity medications in a large cohort of patients using data from electronic health records.
Methods
Pharmacy‐ ...and patient‐level electronic health record data were obtained on 2,248,407 adults eligible for weight‐loss medications from eight geographically dispersed health care organizations.
Results
A total of 29,964 patients (1.3% of total cohort) filled at least one weight‐loss medication prescription. This cohort was 82.3% female, with median age 44.9 years and median BMI 37.2 kg/m2. Phentermine accounted for 76.6% of all prescriptions, with 51.7% of prescriptions being filled for ≥ 120 days and 33.8% filled for ≥ 360 days. There was an increase of 32.9% in medication days for all medications in 2015 compared with 2009. Higher prescription rates were observed in women, black patients, and patients in higher BMI classes. Of 3,919 providers who wrote at least one filled prescription, 23.8% (n = 863) were “frequent prescribers” who wrote 89.6% of all filled prescriptions.
Conclusions
Weight‐loss medications are rarely prescribed to eligible patients. Phentermine accounted for > 75% of all medication days, with a majority of patients filling it for more than 4 months. Less than one‐quarter of prescribing providers accounted for approximately 90% of all prescriptions.
PDF
