1 . A Black adult with a body mass index (BMI) of 28 would be considered
| A) | | underweight. |
| B) | | healthy weight. |
| C) | | overweight. |
| D) | | obese. |
BMI DEFINITIONS OF WEIGHT
| Weight Category | BMI Definition
(kg/m2) |
|---|
| Adult | Adult, East Asian | Pediatrica |
|---|
| 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 |
2 . For most women, abdominal or central obesity is defined as a waist circumference greater than or equal to
| A) | | 88 cm (35 in). |
| B) | | 102 cm (40 in). |
| C) | | 122 cm (48 in). |
| D) | | 190 cm (75 in). |
In some cases, waist circumference is more accurate in
clinical diagnosis, e.g., abdominal obesity. Abdominal or central obesity is defined as waist
circumference ≥102 cm (40 in) in men and ≥88 cm (35 in) in women; and among East Asians, ≥90
cm in men and ≥85 cm in women [22,31]. These are of value only for those with a BMI
between 25.5 and 34.9. It is not useful to measure waist circumference in individuals with BMI
>35, as such patients are already at increased risk.
3 . In 2023, the AMA adopted a policy that recognizes the issues with BMI measurement and suggests that it be used in conjunction with other valid measures of risk. Which of the following is considered a valid measure of risk?
| A) | | Visceral fat |
| B) | | Body composition |
| C) | | Genetic or metabolic factors |
| D) | | All of the above |
In 2023, the AMA adopted a policy that recognizes the issues with BMI measurement (e.g., historical harm, no consideration of gender/ethnicity) and suggests that it be used in conjunction with other valid measures of risk, including but not limited to visceral fat, body adiposity index, body composition, relative fat mass, waist circumference, and genetic or metabolic factors [35].
4 . During 2017–2018, which racial/ethnic group had the highest age-adjusted obesity prevalence in the United States?
| A) | | Hispanic Americans |
| B) | | Non-Hispanic Black Americans |
| C) | | Non-Hispanic Asian Americans |
| D) | | Non-Hispanic White Americans |
During 2017–2018, non-Hispanic Black Americans (49.9%) had the highest age-adjusted obesity prevalence, followed by Hispanic Americans (45.6%), non-Hispanic White Americans (41.4%), and non-Hispanic Asian Americans (16.1%), who also have lower BMI thresholds for adiposopathic (adipocyte and adipose tissue dysfunction) complications [1,29].
5 . Which of the following statements regarding pediatric obesity in the United States is TRUE?
| A) | | Pediatric obesity is no longer increasing. |
| B) | | Pediatric severe obesity has consistently greater prevalence in girls. |
| C) | | Compared with adult obesity, pediatric obesity shows a smaller relative increase over the past 20 years. |
| D) | | Pediatric obesity increased only 11.4% from 1976–1980 to 2003, but more than 300% from 2003 to 2017–2018. |
Although adult obesity is the focus of this course, long-term population trends in pediatric obesity (age 2 to 19 years) provide an informative companion to adult trends. InTable 3, note that pediatric obesity increased >300% from 1976–1980 to 2003, but only 11.4% from 2003 to 2017–2018. Compared with adult obesity, pediatric obesity shows a smaller relative increase over the past 20 years, and pediatric severe obesity has consistently greater prevalence in boys.
6 . A 5-point increase in BMI is strongly associated with increased risk of all of the following, EXCEPT:
| A) | | Thyroid and colon cancers in men |
| B) | | Endometrial and gallbladder cancers in women |
| C) | | Pancreatic and stomach cancers in East Asian individuals |
| D) | | Esophageal adenocarcinoma and renal cancers in both sexes |
Excessive body fat is a cause of 13 cancers, including esophageal, gastric, cardiac, colorectal, liver, gallbladder, pancreas, meningioma, postmenopausal breast, endometrium, ovary, kidney, thyroid, and multiple myeloma [47]. A 5-point increase in BMI is strongly associated with increased risk of thyroid and colon cancers in men, endometrial and gallbladder cancers in women, and esophageal adenocarcinoma and renal cancers in both sexes [46]. From 2004 to 2015, the prevalence of these cancers increased 7% while cancers not known to be related to excessive body fat decreased 13% [46]. Overweight- and obesity-related cancers account for about 40% of all cancers. With approximately 70% of adults overweight or obese, promoting the maintenance of weight loss to decrease cancer risk is critical [47].
7 . Basal energy expenditure is defined as
| A) | | exercise and non-exercise activity. |
| B) | | work-time (occupational) or leisure-time energy expenditure. |
| C) | | the sum of basal energy expenditure and activity energy expenditure. |
| D) | | the minimum energy required to maintain vital physiological functions. |
ETIOLOGY OF THE OBESITY EPIDEMIC
Understanding the relative contribution of lower energy expenditure to the obesity epidemic is a crucial task that requires accurate measurements of energy expenditure [66,67,68]. The terms used in discussions of this concept should be clearly defined [70,71,72]:
Basal energy expenditure: Also known as resting energy expenditure or basal metabolic rate, the minimum energy required to maintain vital physiological functions
Activity energy expenditure: Exercise and non-exercise activity
Physical activity: Work-time (occupational) or leisure-time energy expenditure
Total energy expenditure: Expressed in calories/day, the sum of basal energy expenditure and activity energy expenditure
8 . Increasing activity levels may bring diminishing returns due to
| A) | | decreased activity intensity over time. |
| B) | | compensatory responses in nonactivity energy expenditure. |
| C) | | a predisposition to adiposity because they are weaker energy compensators. |
| D) | | All of the above |
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].
9 . Which of the following statements regarding the role of social contagion in obesity rates is TRUE?
| A) | | Obesity clusters are most likely the result of self-selection. |
| B) | | There is substantial clustering of obesity within social and geographic networks. |
| C) | | Exposure to communities with higher obesity rates has not been found to increase individuals' BMI. |
| D) | | Obesity clustering is clearly the result of causal pathways (e.g., social contagion, shared environments). |
ETIOLOGY OF THE OBESITY EPIDEMIC
There is substantial clustering of obesity within social and geographic networks. Whether this results from causal pathways (e.g., social contagion, shared environments) or self-selection is unclear and was studied in 1,519 military families from 38 military installations around the United States who relocated to counties with obesity rates of 21% to 38% [84]. Exposure to communities with higher obesity prevalence was associated with higher BMI and overweight/obesity in parents and children. Specifically, a 1% higher county obesity rate was associated with 5% higher odds of obesity in parents and 4% higher odds of overweight/obesity in children [84].
10 . Which of the following statements best characterizes the impact of sugar on individual and population obesity?
| A) | | The slower gastric emptying time of sugar-sweetened beverages may lead to fatty accumulation in the liver. |
| B) | | There is strong, consistent evidence that high sugar consumption leads to obesity and related metabolic diseases. |
| C) | | High sugar intake from sugar-sweetened beverages has the same impact on BMI and metabolism as sugar-containing foods (i.e., solid sugars). |
| D) | | High sugar-sweetened beverage consumption is dose dependently associated with increased risk of cardiovascular disease morbidity and mortality through weight gain. |
ETIOLOGY OF THE OBESITY EPIDEMIC
Evidence for the mainstream view that high sugar consumption leads to obesity and related metabolic diseases is inconsistent, and high sugar intake from s
ugar-sweetened beverages may differ from sugar-containing foods (i.e., solid sugars) in BMI/metabolic impact [89].
In a review of prospective evidence, most studies linking high sugar intake to adverse health outcomes examined sugar-sweetened beverages, while studies of solid sugar intake mostly reported null findings. High sugar-sweetened beverage consumption was dose dependently associated with increased risks of cardiovascular disease morbidity and mortality through weight gain; solid sugar sources (e.g., ice cream) were not [89,90].
Sugar-sweetened beverages may be more likely to induce metabolic syndrome. The faster gastric emptying time of sugar-sweetened beverages and higher absorption of its fructose component may lead to fatty accumulation in the liver. Compared with solid sugars, sugar-sweetened beverages induce less satiety and may subsequent cause overeating. The gut can convert low-concentration fructose to glucose, but transports high-concentration fructose (e.g., in sugar-sweetened beverages) to the liver [89].
Increased lipogenesis and circulating triglycerides, very-low-density cholesterol, and uric acid associated with high sugar-sweetened beverage intake may induce hyperglycemia, glucose intolerance and dyslipidemia to increase risks of type 2 diabetes and cardiovascular disease. High intake of fructose-sweetened beverages may disrupt the production of appetite control hormones (decreasing leptin and insulin, increasing ghrelin), suggesting different effects on metabolic and endocrine health of liquid versus solid sugars [89].
Individuals who ingest high dietary sugar often have other unhealthy behaviors that may contribute to the pathogenesis of obesity and related disorders, complicating causal inferences. Although definitive evidence is needed, and reducing sugar remains a general recommendation, there is evidence of greater health risks with sugar-sweetened beverages that might not be comparable to those with sugar in food [89,91].
11 . Endocrine-disrupting chemicals
| A) | | are rarely encountered in all environments. |
| B) | | block adiposity by altering programming of fat cell development, decreasing energy storage in fat tissue. |
| C) | | interfere with hormone action to dysregulate endocrine function, insulin signaling, and/or adipocyte function. |
| D) | | are present throughout life, but advanced age is the most sensitive period for endocrine-disrupting chemicals to impact weight gain. |
ETIOLOGY OF THE OBESITY EPIDEMIC
Endocrine-disrupting chemicals interfere with hormone action to dysregulate endocrine function, insulin signaling, and/or adipocyte function. Adipose tissue is a true endocrine organ and is therefore highly susceptible to disturbance by endocrine-disrupting chemicals. Obesogenic endocrine-disrupting chemicals promote adiposity by altering programming of fat cell development, increasing energy storage in fat tissue, and interfering with neuroendocrine control of appetite and satiety [17,18,48,77,96,97].
Endocrine-disrupting chemicals have become ubiquitous in our environment. Exposure occurs throughout life, but development is the most sensitive period for endocrine-disrupting chemicals to impact future weight gain across the lifespan and generations, and endocrine-disrupting chemicals can act via epigenetic mechanisms. There is an urgent need to understand how exposures to certain endocrine-disrupting chemicals may predispose the population to obesity [48,77,96,98,99].
12 . Which of the following statements regarding energy balance is FALSE?
| A) | | The small storage capacity of fat can only cover overnight energy needs during sleep. |
| B) | | As a substrate for energy metabolism, fat is last in the hierarchy that determines fuel selection. |
| C) | | Excess energy is stored as fat in adipose depots, carbohydrate (as glycogen) in liver, or protein in muscle. |
| D) | | The energy density of adipose tissue is nearly 10-fold greater than liver (glycogen) or muscle (protein). |
THE REGULATION OF BODY WEIGHT
Excess energy is stored as fat in adipose depots, carbohydrate (as glycogen) in liver, or protein in muscle. The energy density of adipose tissue is nearly 10-fold greater than liver (glycogen) or muscle (protein). The small storage capacity for carbohydrate can cover overnight energy needs during sleep. The larger energy stores of fat are mobilized to cover longer-term energy shortages [70,102,103].
However, as a substrate for energy metabolism, fat is last in the hierarchy that determines fuel selection; it is mostly stored before oxidation and is less likely to be oxidized than carbohydrate or protein. Body-fat mass and oxidation of dietary fat are inversely related—higher fat mass lowers the oxidation rate of dietary fat [70,102,103]. Energy expenditure is the sum of ATP generated by oxidizing monomers to drive physiological processes.
13 . The biological pressure to gain weight is a consequence of both
| A) | | genetic factors and historical starvation protection. |
| B) | | increased appetite and suppressed energy expenditure. |
| C) | | decreased physical activity and increased insulin sensitivity. |
| D) | | environmental pressures and dysregulated gut microbiome. |
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].
14 . The Obesity Medicine Association (OMA) has identified four pillars of obesity care. These pillars are
| A) | | psychotherapy, pharmacotherapy, environmental interventions, and lifestyle changes. |
| B) | | healthful nutrition, physical activity, behavior modification, and medical management. |
| C) | | cognitive-behavioral therapy, dialectical behavioral therapy, exercise therapy, and insulin. |
| D) | | antiobesity medications, surgical interventions, hormone therapy, and medical nutrition therapy. |
OVERVIEW OF CLINICAL MANAGEMENT
The OMA states that obesity is a serious and multifactorial disease that requires patient access to comprehensive care, including the four pillars of healthful nutrition, physical activity, behavior modification, and medical management with antiobesity medications and surgical interventions. Comprehensive care of obesity is not only about reducing weight but also about improving the health of patients [122].
15 . Which of the following antidepressants is considered to be weight-reducing?
| A) | | Paroxetine |
| B) | | Bupropion |
| C) | | Mirtazapine |
| D) | | Amitriptyline |
OVERVIEW OF CLINICAL MANAGEMENT
OBESOGENIC MEDICATIONS AND WEIGHT-NEUTRAL OR -REDUCING ALTERNATIVES
| Clinical Condition or Drug Class | Weight-Promoting | Weight Neutral | Weight-Reducing |
|---|
| Type 2 diabetes with obesity |
| Pioglitazone | | Sulfonylureas | | Insulin |
| DPP-4 inhibitors |
| Metformin | | SGLT2 inhibitors | | GLP-1R agonists |
|
| Antidepressants |
| Paroxetine | | Amitriptyline | | Mirtazapine |
| — |
|
| Atypical antipsychotics |
| Olanzapine | | Quetiapine | | Risperidone |
| Ziprasidone | — |
| Anticonvulsants and mood stabilizers |
| Divalproex | | Carbamazepine | | Gabapentin |
|
|
|
| Inflammatory rheumatic diseases | Corticosteroids |
| — |
| DMARDs = disease-modifying antirheumatic drugs,
DPP-4 = dipeptidyl peptidase-4, NSAIDs = nonsteroidal anti-inflammatory drugs, SGLT2
= sodium-glucose cotransporter-2. |
16 . Which of the following is a preferred agent for the patient with bipolar disorder for whom weight loss or maintenance is a concern?
| A) | | Quetiapine |
| B) | | Olanzapine |
| C) | | Ziprasidone |
| D) | | Risperidone |
OVERVIEW OF CLINICAL MANAGEMENT
OBESOGENIC MEDICATIONS AND WEIGHT-NEUTRAL OR -REDUCING ALTERNATIVES
| Clinical Condition or Drug Class | Weight-Promoting | Weight Neutral | Weight-Reducing |
|---|
| Type 2 diabetes with obesity |
| Pioglitazone | | Sulfonylureas | | Insulin |
| DPP-4 inhibitors |
| Metformin | | SGLT2 inhibitors | | GLP-1R agonists |
|
| Antidepressants |
| Paroxetine | | Amitriptyline | | Mirtazapine |
| — |
|
| Atypical antipsychotics |
| Olanzapine | | Quetiapine | | Risperidone |
| Ziprasidone | — |
| Anticonvulsants and mood stabilizers |
| Divalproex | | Carbamazepine | | Gabapentin |
|
|
|
| Inflammatory rheumatic diseases | Corticosteroids |
| — |
| DMARDs = disease-modifying antirheumatic drugs,
DPP-4 = dipeptidyl peptidase-4, NSAIDs = nonsteroidal anti-inflammatory drugs, SGLT2
= sodium-glucose cotransporter-2. |
17 . In treating obesity as a chronic disease, the essential goal of weight-loss therapy is
| A) | | the quantity of weight loss. |
| B) | | major lifestyle changes in support of established goals. |
| C) | | to mitigate metabolic diseases and lose a certain amount of weight. |
| D) | | the prevention and treatment of complications to enhance health and mitigate morbidity and mortality. |
OVERVIEW OF CLINICAL MANAGEMENT
In treating obesity as a chronic disease, the essential goal of weight-loss therapy is not the quantity of weight loss per se, but rather the prevention and treatment of complications to enhance health and mitigate morbidity and mortality. This paradigm of care is the basis of the complications-centric AACE/ACE obesity guideline and the diagnostic term adiposity-based chronic disease (ABCD) [3].
18 . A patient who achieves 7% reduction in body weight should expect to see
| A) | | type 2 diabetes remission. |
| B) | | remission in obstructive sleep apnea. |
| C) | | improved physical and biomechanical function. |
| D) | | nonalcoholic steatohepatitis (NASH) improvement. |
OVERVIEW OF CLINICAL MANAGEMENT
The estimated weight reduction required to improve morbidity and mortality outcomes are [3]:
5% to 10% weight reduction: Improved physical and biomechanical function, type 2 diabetes prevention
10% to 15% weight reduction: Cardiovascular disease risk reduction and remission/reduction in obstructive sleep apnea, hypertension, type 2 diabetes hyperglycemia
≥16% weight reduction: Type 2 diabetes remission, NASH improvement
19 . All antiobesity medications are considered pregnancy risk factor category
Except for setmelanotide and metreleptin, all antiobesity medications are approved as adjuncts to a reduced-calorie diet and increased physical activity for chronic weight management in adults with obesity (BMI ≥30) or overweight (BMI ≥27) with at least one weight-related complication, such as hypertension, type 2 diabetes, or dyslipidemia [137]. All antiobesity medications are considered pregnancy risk factor category X drugs and should not be prescribed to a patient who is pregnant, breastfeeding, or trying to conceive [124].
20 . Setmelanotide is contraindicated for patients with
| A) | | polygenic obesity. |
| B) | | nongenetic causes of obesity. |
| C) | | benign variants of the gene mutations. |
| D) | | All of the above |
Setmelanotide is the first antiobesity medication approved specifically for the treatment of rare genetic conditions associated with obesity. The drug binds to melanocortin-4 receptor (MC4R) in the hypothalamus, downstream of the leptin signaling pathway [135]. Setmelanotide re-establishes the activity of the MC4R pathway, thus reducing hunger and promoting body weight loss by lowering caloric intake and increasing energy expenditure [140].
21 . Which of the following is a common adverse effect of phentermine HCl?
| A) | | Diarrhea |
| B) | | Dry mouth |
| C) | | Hyperactivity |
| D) | | Abdominal pain |
Common adverse effects in clinical trials include dry mouth (55%) and insomnia (34%), without significant differences in systolic or diastolic blood pressure, headache, or palpitations between phentermine and placebo groups [131]. Other common side effects include dizziness, flushing, fatigue, and constipation [92]. Phentermine is not recommended for patients with cardiovascular disease, and uncontrolled hypertension is a relative contraindication. Phentermine is available in 8-mg tablets taken three times daily and in 15-mg, 30-mg, and 37.5-mg capsules taken once daily [131].
22 . Gelesis100 acts
| A) | | by binding to melanocortin-4 receptor (MC4R) in the hypothalamus, downstream of the leptin signaling pathway. |
| B) | | as a transient, space-occupying device in a swallowed capsule that absorbs water to expand and fill up the stomach to induce satiety. |
| C) | | as a centrally acting sympathomimetic, with therapeutic effects mediated through increased levels of norepinephrine in the hypothalamus. |
| D) | | as a pancreatic and gastric lipase inhibitor that blocks the lipase-catalysed breakdown and absorption of around 30% of dietary fats. |
Gelesis100 superabsorbent hydrogel is ingested orally, similar to drugs, but is regulated by the FDA as a class II medical device, because it acts mechanically as a transient, space-occupying device in a swallowed capsule that absorbs water to expand and fill up the stomach to induce satiety. Gelesis100 is FDA approved for patients with BMI 25–40. Recommended dosing is three capsules (2.25 g/dose) with water before both lunch and dinner [30,123].
23 . Why does the AGA obesity guideline suggest against the use of orlistat?
| A) | | The adverse effects are considered very bothersome. |
| B) | | There is a high treatment discontinuation rate with this agent. |
| C) | | Overall weight loss with orlistat is of a small magnitude (2.78%). |
| D) | | All of the above |
Overall weight loss with orlistat is of a small magnitude (2.78%). In contrast, the adverse effects are considered very bothersome and result in high treatment discontinuation rates. Therefore, the 2022 AGA obesity guideline suggests against the use of orlistat [123].
24 . Each naltrexone/bupropion tablet contains
| A) | | 8 mg naltrexone and 90 mg bupropion. |
| B) | | 18 mg naltrexone and 9 mg bupropion. |
| C) | | 80 mg naltrexone and 190 mg bupropion. |
| D) | | 90 mg naltrexone and 8 mg bupropion. |
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].
25 . Which of the following agents is a glucagon-like peptide-1 receptor agonist (GLP-1 RA)?
| A) | | Orlistat |
| B) | | Topiramate |
| C) | | Semaglutide |
| D) | | Diethylpropion |
Endogenous GLP-1 has a very short half-life due to rapid enzymatic degradation by dipeptidyl peptidase-4 (DPP-4). Synthetic analogs modify the GLP-1 structure to resist DPP-4 by amino acid substitutions in the protein structure or by attachment to large proteins such as albumin or immunoglobulin [147]. Liraglutide shares a 97% amino acid sequence similarity with human GLP-1, while semaglutide has a 94% similarity. Compared with liraglutide, the substantially longer half-life and greater weight loss efficacy of semaglutide may involve differences in the attached fatty acids [139].
26 . As of 2023, what is the only oral GLP-1 RA approved for the treatment of type 2 diabetes?
| A) | | Liraglutide |
| B) | | Tirzepatide |
| C) | | Dulaglutide |
| D) | | Semaglutide |
As of 2023, oral semaglutide is the only oral GLP-1 RA approved for the treatment of type 2 diabetes, at a dosage of 14 mg per day (Rybelsus). Higher doses are being investigated for weight effects in obesity without type 2 diabetes in the OASIS trials [147]. The phase 3 OASIS 1 trial assessed oral, once-daily semaglutide 50 mg in 667 adults with obesity without type 2 diabetes. After 68 weeks, participants on semaglutide had greater mean weight loss (15.1% vs 2.4%), weight loss ≥10% (69% vs 12%), ≥15% (54% vs 6%), and ≥20% (34% vs 3%) compared with placebo. Adverse effects (mostly mild-to-moderate gastrointestinal symptoms) occurred in 80% on semaglutide and 46% on placebo. These outcomes mirror those of semaglutide 2.4 mg subcutaneous [153]. Phase 3 trials have completed, and submission for FDA approval is expected in 2024. Of note, there are currently no registered clinical trials comparing oral with subcutaneous semaglutide for obesity [92].
27 . Which of the following statements regarding tirzepatide and oral contraceptives is FALSE?
| A) | | Tirzepatide has not been found to significantly alter the efficacy of oral contraceptives. |
| B) | | Patients taking oral contraceptives should switch to tirzepatide as the preferred antiobesity medication. |
| C) | | Tirzepatide is known to reduce the efficacy of oral contraceptive medications due to hormonal blocking properties. |
| D) | | Patients should switch from oral to nonoral contraceptives for the first four weeks when tirzepatide is initiated. |
Tirzepatide is known to reduce the efficacy of oral contraceptive medications due to delayed gastric emptying. This delay is largest after the first dose, so patients should switch from oral to nonoral contraceptives for the first four weeks when tirzepatide is initiated [162]. Patients should be counseled regarding the risk of unintended pregnancy and the necessity of other contraceptive methods.
28 . Which of the following investigational antiobesity medications is a triple agonist at GCGR, GIPR, and GLP-1R?
| A) | | Retatrutide |
| B) | | Cagrilintide |
| C) | | Survodutide |
| D) | | Bimagrumab |
A triple agonist may provide even more effective glycemic control and weight loss compared to single or dual receptor agonists. Retatrutide is a triple agonist at GCGR, GIPR, and GLP-1R [139]. A phase 2 dose-response study evaluated retatrutide in 338 adults with obesity [165]. At 48 weeks retatrutide 1 mg, 4 mg, 8 mg, and 12 mg led to 8.7%, 17.1%, 22.8%, and 24.2% mean weight loss, compared with a 2.1% reduction with placebo. Among those who received 8 mg or 12 mg retatrutide, 91% and 93% experienced weight loss ≥10% and 75% and 83% experienced weight loss ≥15% (compared with 9% and 2% among those receiving placebo).
29 . Given the decreased likelihood of obesity in current cannabis users, which medication is being studied for possible antiobesity uses?
| A) | | THC |
| B) | | CBD |
| C) | | Nabilone |
| D) | | Dronabinol |
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.
30 . What is the recommended first-line antiobesity medication for obesity management?
| A) | | Liraglutide 1.8 mg daily |
| B) | | Semaglutide 2.4 mg weekly |
| C) | | Orlistat 60 mg three times daily |
| D) | | Phentermine/topiramate 7.5 mg/46 mg daily |
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.
31 . After initiating any antiobesity medication, the weight loss by what point is considered an indicator of treatment response?
| A) | | 2 weeks |
| B) | | 8 weeks |
| C) | | 12 weeks |
| D) | | 24 weeks |
After initiating any antiobesity medication, the weight lost by 12 weeks is considered an indicator of treatment response. If adherence can be ensured and 5% weight loss is not achieved after three months, the drug can be given at an increased dose, combined with another drug, stopped altogether, or replaced with a new drug [135].
32 . Which of the following strategies has been shown to minimize adverse effects of GLP-1 RAs?
| A) | | Slow dose escalation |
| B) | | Counseling on expected adverse effects and their duration |
| C) | | Using a multidisciplinary team approach to provide regular follow-up and guidance as patients initiate the medication |
| D) | | All of the above |
When starting GLP-1 agonists, several strategies can promote success and decrease risk of discontinuation. Strategies to minimize adverse effects include slow dose escalation, counseling on expected adverse effects and their duration, and using a multidisciplinary team approach (including the primary care provider, pharmacists, nurses, and medical assistants) to provide regular follow-up and guidance as patients initiate the medication. It is particularly important to discuss gastrointestinal adverse effects, as patients who are not expecting these adverse effects may prematurely discontinue the medication [131].
33 . Which of the following antiobesity medications is the least expensive?
| A) | | Orlistat |
| B) | | Liraglutide |
| C) | | Phentermine |
| D) | | Phentermine-topiramate ER |
FDA-APPROVED ANTIOBESITY MEDICATIONS AND RETAIL COST, 2023
| Agent | Typical Maintenance Dose | Average Retail Price, 30-Day Supply |
|---|
| Phentermine | 8–37.5 mg daily | $11.31 |
| Diethylpropion | 75 mg daily | $48.73 |
| Orlistat |
| 60 mg TID (OTC) | | 120 mg TID (Rx) |
|
| ~ $45.00 (Alli) | | $808.06 (Xenical) |
|
| Naltrexone/bupropion ER | 16/180 mg BID | $308.00 |
| Phentermine/topiramate ER | 7.5–15/46–92 mg daily | $231.07 |
| Liraglutide 3.0 mg | Once daily | $1,064.86 |
| Semaglutide 2.4 mg | Once weekly | $1,576.73 |
| Tirzepatide (2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, 15 mg) | Once weekly | $1,059.87 |
| BID = twice daily, OTC = over the counter, Rx =
prescription, TID = three times daily. |
34 . Which of the following metabolic and bariatric surgery (MBS) options is optimally suited for a patient with lower BMI and no metabolic disease?
| A) | | Sleeve gastrectomy |
| B) | | Roux-en-Y gastric bypass (RYGB) |
| C) | | Laparoscopic adjustable gastric banding (LAGB) |
| D) | | Biliopancreatic diversion with duodenal switch (BPD/DS) |
BARIATRIC SURGICAL PROCEDURES AND DEVICES
ASMBS-ENDORSED SURGICAL APPROACHES
| Procedure | Optimally Suited For | Percent 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 |
|
35 . Which of the following statements regarding indications for MBS is TRUE?
| A) | | Patients older than 70 years of age should not be offered MBS. |
| B) | | MBS is recommended for patients with BMI of 40 only in those with at least one obesity-related complication. |
| C) | | A BMI more than 25 suggests clinical obesity in Asian patients, and those with BMI more than 27.5 should be offered MBS. |
| D) | | MBS should be considered in patients with BMI 25–30 who do not achieve substantial or durable weight loss. |
BARIATRIC SURGICAL PROCEDURES AND DEVICES
The universally applied threshold for bariatric surgery (i.e., BMI >40 or BMI >35 with comorbidities) was set in 1991 by the National Institutes of Health. With significant advances in obesity science and safer, more effective bariatric approaches supported by three decades of evidence, this indication no longer reflects best practice and was replaced with new practice guidelines by the ASMBS in 2022 [126]. According to the ASMBS, MBS is recommended for [126]:
Patients with BMI ≥35, regardless of presence, absence, or severity of
obesity-related complication
Patients with type 2 diabetes and BMI ≥30
The BMI thresholds should be adjusted in Asian populations [126]. A BMI >25 suggests clinical obesity in these patients, and those with BMI >27.5 should be offered MBS.
The ABMS asserts that there is no upper age limit to MBS [126]. Older patients who could benefit from MBS should be considered after careful assessment of comorbidities and frailty.
MBS is also an effective treatment of clinically severe obesity in patients who need other specialty surgery, such as joint arthroplasty, abdominal wall hernia repair, or organ transplantation. Severe obesity is a chronic disease requiring long-term management after primary MBS, which may include revisional surgery or adjuvant antiobesity medication to achieve or sustain desired treatment effects [126].
36 . What should MBS candidates and patients be counseled regarding tobacco use?
| A) | | Tobacco use, and cigarette smoking in particular, must be avoided at all times by all patients. |
| B) | | Patients who smoke cigarettes should stop as early as possible, preferably one year but at the very least six weeks before MBS. |
| C) | | Tobacco use should be avoided post-MBS given the increased risk of poor wound healing, anastomotic ulcer, and overall impaired health. |
| D) | | All of the above |
BARIATRIC SURGICAL PROCEDURES AND DEVICES
Tobacco use, and cigarette smoking in particular, must be avoided at all times by all patients. Patients who smoke cigarettes should stop as early as possible, preferably one year but at the very least six weeks before MBS. In addition, tobacco use must be avoided post-MBS given the increased risk of poor wound healing, anastomotic ulcer, and overall impaired health. Structured intensive smoking cessation programs are preferable to general advice and should be implemented [125].
37 . What is the criterion-standard MBS with the longest-term safety and efficacy data?
| A) | | Sleeve gastrectomy |
| B) | | Roux-en-Y gastric bypass (RYGB) |
| C) | | Laparoscopic adjustable gastric banding (LAGB) |
| D) | | Biliopancreatic diversion with duodenal switch (BPD/DS) |
BARIATRIC SURGICAL PROCEDURES AND DEVICES
RYGB is the criterion-standard MBS with the longest-term safety and efficacy data [226]. In this procedure, the stomach is divided; a small gastric pouch is anastomosed (cross-connected) to a severed "roux" limb of small bowel jejunum through which food passes, bypassing the larger gastric remnant, duodenum, and proximal jejunum [227]. This approach has been found to dramatically improve type 2 diabetes and is part of the treatment algorithm for uncontrolled type 2 diabetes in patients with BMI ≥35. It is also associated with modestly greater weight loss and improvements in metabolic disease compared with sleeve gastrectomy. It also improves GERD [127,135].
38 . All of the following intragastric balloon devices are ASMBS-endorsed and FDA-approved for six-month dwell-time, EXCEPT:
| A) | | Orbera |
| B) | | Obalon |
| C) | | ReShape Duo |
| D) | | TransPyloric Shuttle |
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].
Obalon uses up to three deflated balloons, swallowed as capsules. Gas is then injected into the balloons under x-ray observation. Weight loss typically is about 6.6%. In a registry of 1,343 patients, weight loss was 10.0% in the indicated BMI category (BMI 30–40), 10.3% in BMI 25–30, and 9.3% in BMI >40. Adverse event (14%) and severe adverse event (0.15%) rates included seven balloon deflations, none of which resulted in obstruction [246].
Common adverse effects are mainly nausea and mild abdominal pain, and serious events are rare. However, leaking occurs more easily with gas-filled than liquid-filled balloons, and leaking balloons must be removed by gastroscopy, a disadvantage with Obalon [228,245].
With the ReShape Duo balloon device, two balloons are connected by a soft silicone rod. Each balloon is filled with 450 mL of fluid. The two-balloon design is intended to prevent premature failure, better conform to the stomach curvature, and improve patient tolerability. The ReShape device significantly reduces severe adverse effects rates compared with Orbera, but postoperative adverse event rates remain relatively high [228]. Average weight loss is approximately 6.8% [135].
39 . What effect does ghrelin have on energy balance and obesity?
| A) | | It increases satiety. |
| B) | | It increases food consumption and reward. |
| C) | | It decreases body weight and plasma lipids. |
| D) | | It decreases gastric emptying and food intake. |
APPENDIX: PHYSIOLOGY AND PATHOPHYSIOLOGY
HORMONE, METABOLIC, AND PEPTIDE SIGNALS OF SATIETY, HUNGER AND ADIPOSITY, BY
PERIPHERAL TISSUE ORIGIN
| Hormone | Receptor Locations in CNS | Effects 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. |
40 . Brown adipose tissue
| A) | | comprises 15% to 25% of body fat. |
| B) | | has more mitochondria (thus its brown appearance). |
| C) | | includes subcutaneous adipose tissue and visceral (abdominal) adipose tissue. |
| D) | | is absent in neonates but increases in adults and increases further in obese adults. |
APPENDIX: PHYSIOLOGY AND PATHOPHYSIOLOGY
Part of understanding obesity as a disease is recognizing that adipocytes and adipose tissue have vital functions beyond energy storage alone [128]. Adipose tissue is mostly comprised of adipocytes, regulates multiple body processes critical to energy and metabolic homeostasis, and is functionally classified into two types: white and brown [128,285]. White adipose tissue is an active endocrine and immune organ that includes subcutaneous adipose tissue and visceral (abdominal) adipose tissue and primarily stores energy. However, subcutaneous adipose tissue contains brown-like inducible adipocytes that perform mitochondrial and thermogenic functions and burn fat [286].
Brown adipose tissue, comprising 1% to 2% of body fat, has more mitochondria (thus its brown appearance) and is abundant in neonates but decreases in adults and decreases further in obese adults [286]. Brown adipose tissue produces heat energy, termed thermogenesis, uponβ-adrenergic stimulation [287].
