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Pharmacologic and Medical Advances in Obesity Management

Course #94280 - $90-

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  • Participation Instructions
    • Review the course material online or in print.
    • Complete the course evaluation.
    • Review your Transcript to view and print your Certificate of Completion. Your date of completion will be the date (Pacific Time) the course was electronically submitted for credit, with no exceptions. Partial credit is not available.
  1. A Black patient with a body mass index of 26 is considered overweight.

    DEFINITIONS OF OBESITY

    BMI DEFINITIONS OF WEIGHT

    Weight CategoryBMI Definition (kg/m2)
    AdultAdult, East AsianPediatrica
    Underweight <18.5 <18.5 <5th percentile
    Normal 18.5–24.9 18.5–22.9 5th–85th percentile
    Overweight 25–29.9 23–24.9 ≥85th percentile
    Class I obesity 30–34.9 25–29.9

    Obesity: ≥95th percentile

    Class II obesity 35–39.9 30–34.9
    Class III obesity (severe obesity) ≥40 ≥35 Severe obesity: ≥120% of the 95th percentile
    aBased on sex-specific BMI for age
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  2. Increasing activity levels may bring diminishing returns due to compensatory responses in nonactivity energy expenditure.

    ETIOLOGY OF THE OBESITY EPIDEMIC

    Increasing activity levels may bring diminishing returns due to compensatory responses in nonactivity energy expenditure [66]. In 1,754 adults with DLW measured seven years apart, only 72% of the extra calories burned during activity translated into extra calories expended that day, because the body offset the calories burned in activities by 28%. Among those with BMI ≥34, compensation of burned activity calories increased to 46% [72].

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  3. The biological pressure to gain weight is a consequence of both increased appetite and suppressed energy expenditure as the body attempts to restore energy homeostasis.

    THE REGULATION OF BODY WEIGHT

    Because both sides of the energy balance equation are affected after weight loss, the biological pressure to gain weight is a consequence of both increased appetite and suppressed energy expenditure as the body attempts to restore energy homeostasis [15,108]. Termed metabolic adaptation, this defense of established adiposity against weight loss recapitulates a physiological response that signals potential starvation [69,104].

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  4. Paroxetine is considered to be a weight-reducing antidepressant.

    OVERVIEW OF CLINICAL MANAGEMENT

    OBESOGENIC MEDICATIONS AND WEIGHT-NEUTRAL OR -REDUCING ALTERNATIVES

    Clinical Condition or Drug ClassWeight-PromotingWeight NeutralWeight-Reducing
    Type 2 diabetes with obesity
    Pioglitazone
    Sulfonylureas
    Insulin
    DPP-4 inhibitors
    Metformin
    SGLT2 inhibitors
    GLP-1R agonists
    Antidepressants
    Paroxetine
    Amitriptyline
    Mirtazapine
    Bupropion
    Fluoxetine
    Atypical antipsychotics
    Olanzapine
    Quetiapine
    Risperidone
    Ziprasidone
    Anticonvulsants and mood stabilizers
    Divalproex
    Carbamazepine
    Gabapentin
    Lithium
    Lamotrigine
    Zonisamide
    Topiramate
    Inflammatory rheumatic diseases Corticosteroids
    DMARDs
    NSAIDs
    DMARDs = disease-modifying antirheumatic drugs, DPP-4 = dipeptidyl peptidase-4, NSAIDs = nonsteroidal anti-inflammatory drugs, SGLT2 = sodium-glucose cotransporter-2.
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  5. Each naltrexone/bupropion tablet contains naltrexone 90 mg plus bupropion 8 mg.

    ANTIOBESITY MEDICATIONS

    Each naltrexone/bupropion tablet contains naltrexone 8 mg plus bupropion 90 mg. The target maintenance dose of 4 tablets daily (naltrexone 32 mg/bupropion 360 mg) daily is shortened with the prolonged-release formulation (NB32). The initial dose is 1 tablet daily, increased stepwise to the target of 2 tablets twice daily. Typical weight loss seen in practice is around 5% to 6% with NB32s [131].

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  6. Given this decreased likelihood of obesity in current cannabis users, research has begun to explore how the endocannabinoid system can be manipulated to promote weight loss and improve metabolic health.

    ANTIOBESITY MEDICATIONS

    However, a meta-analysis of data from the National Epidemiologic Survey on Alcohol and Related Conditions and the National Comorbidity Survey-Replication found a decreased prevalence of obesity among current users of cannabis (≥3 days per week) of 14.3% and 17.2%, respectively [185]. Given this decreased likelihood of obesity in current cannabis users, research has begun to explore how the endocannabinoid system can be manipulated to promote weight loss and improve metabolic health.

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  7. Semaglutide 2.4 mg weekly is recommended as the first-line antiobesity medication for obesity management.

    ANTIOBESITY MEDICATIONS

    Given the significantly greater weight loss with semaglutide (15%) than other currently approved antiobesity medications (6% to 10%) and with 69% and 50% of subjects attaining weight loss ≥10% and >15%, respectively, semaglutide 2.4 mg weekly is recommended as the first-line antiobesity medication for obesity management [131]. Weight-loss goals for most individuals with obesity should be at least 10% or more, which is now achievable with current antiobesity medications.

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  8. Sleeve gastrectomy is optimally suited for a patient with lower BMI and no metabolic disease.

    BARIATRIC SURGICAL PROCEDURES AND DEVICES

    ASMBS-ENDORSED SURGICAL APPROACHES

    ProcedureOptimally Suited ForPercent Excess Weight Lossa
    At 2 years At 10 years
    Roux-en-Y gastric bypass (RYGB) Higher BMI, GERD, diabetes 55% to 75% 52% to 69%
    Sleeve gastrectomy Metabolic disease 50% to 70% 67% to 71%
    Laparoscopic adjustable gastric banding (LAGB) Lower BMI, no metabolic disease 30% to 50% 38% to 47%
    Biliopancreatic diversion with duodenal switch (BPD/DS) Super-obesity (BMI ≥50), diabetes 63% to 80+% 68%
    Single anastomosis duodenal-ileal bypass with sleeve (SADI-S) Super-obesity 74% NA
    One-anastomosis gastric bypass (OAGB) Higher BMI, diabetes 68% to 80% 73%
    BMI = body mass index, GERD = gastroesophageal reflux disease, NA = not available.
    aMean average
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  9. Orbera is an ASMBS-endorsed intragastric balloon device FDA-approved for six-month dwell-time.

    BARIATRIC SURGICAL PROCEDURES AND DEVICES

    Three intragastric balloon devices are ASMBS-endorsed and FDA-approved for six-month dwell-time. The Orbera and Reshape balloons are both filled with methylene blue and saline. A leak or rupture releases the dye, which turns the urine blue to rapidly reveal the problem [135,228].

    Contraindications to intragastric balloon devices use include prior abdominal or weight-reduction surgery, inflammatory bowel disease, obstructive disorders, GI ulcers, severe reflux, prior GI bleeding, severe liver disease, coagulopathy, ongoing alcohol use disorder, or intestinal varices, stricture, or stenosis [239,245].

    Orbera, the most widely and longest used intragastric balloon device, is an endoscopically inserted single gastric balloon filled with 400–750 mL of fluid [245]. In a meta-analysis of 1,683 patients, weight loss at 6 and 12 months was 13.2% and 11.3%, respectively. Common adverse events were pain (34%), nausea (29%), GERD (18%), gastric mucosal erosion (12%), and balloon removal due to intolerability (7.5%). Severe events included gastric ulcers (2.0%), balloon displacement (1.4%), small bowel obstruction (0.3%), perforation (0.1%), and death (0.08%). All perforations occurred in patients with prior gastric surgery; all deaths were secondary to perforation or aspiration. Thus, individualized, detailed risk assessment is necessary for patients planning to undergo intragastric balloon device placement [228]. Orbera early removal is also associated with use of selective serotonin or serotonin-norepinephrine reuptake inhibitors (SSRIs/SNRIs) [125].

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  10. Ghrelin increases food consumption and reward.

    APPENDIX: PHYSIOLOGY AND PATHOPHYSIOLOGY

    HORMONE, METABOLIC, AND PEPTIDE SIGNALS OF SATIETY, HUNGER AND ADIPOSITY, BY PERIPHERAL TISSUE ORIGIN

    HormoneReceptor Locations in CNSEffects on Energy Balance and Obesity
    Adipocyte origin
    Adiponectin Hypothalamus ↓Body weight, plasma lipids
    Leptin ARC ↓Food intake, body weight
    Pancreatic cell origin
    Amylin ARC, AP, VTA, striatum
    ↑Satiety
    ↓Gastric emptying, food intake
    Glucagon (GCG) ARC, NTS ↑Satiety, glycogenolysis, gluconeogenesis
    Insulin ARC ↓Food intake, body weight
    Pancreatic polypeptide (PP) Hypothalamus, NTS
    ↑Satiety
    ↓Gastric emptying
    Enteroendocrine cell origin
    Cholecystokinin (CCK) Hypothalamus, NTS
    ↑Satiety
    ↓Gastric emptying/motility
    Ghrelin ARC ↑Food consumption and reward
    GIP ARC, PVH, DMH
    ↓Food intake
    ↑LPL, postprandial insulin
    Glucagon-like peptide-1 (GLP-1) ARC, NTS, AP, striatum
    ↑Satiety, postprandial insulin
    ↓Gastric emptying/motility, food reward
    Oxyntomodulin (OXM) Hypothalamus
    ↑Satiety
    ↓Gastric emptying, food intake
    Peptide tyrosine tyrosine (PYY) ARC, NTS
    ↑Satiety
    ↓Gastric emptying/motility
    AP = area postrema, ARC = arcuate nucleus of the hypothalamus, CNS = central nervous system, DMH = dorsomedial hypothalamus, GHSR, growth hormone secretagogue receptor, GIP, glucose-dependent insulinotropic polypeptide, NTS = nucleus tractus solitarius, PVH = paraventricular nucleus of the hypothalamus, VTA = ventral tegmental area.
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  • Back to Course Home
  • Participation Instructions
    • Review the course material online or in print.
    • Complete the course evaluation.
    • Review your Transcript to view and print your Certificate of Completion. Your date of completion will be the date (Pacific Time) the course was electronically submitted for credit, with no exceptions. Partial credit is not available.