Obesity Flashcards
What is obesity?
obesity is a complex heterogenous disorder that places individuals at increased risk for adverse health consequences from the accumulation of excess and abnormal body fat (adiposity). It is a progressive and relapsing condition; both the World Obesity Federation and the CMA classify obesity as a chronic medical disease
What is BMI?
defines height/weight characteristics in adults to classify them into groups
-BMI = weight (kg) / height (m2)
What are the BMI classes?
< 18.5 = underweight
18.5 to < 25 = healthy range
25 to < 30 = overweight
-class 1 obesity = 30-34.9
-class 2 obesity = 35-39.9
-class 3 = > 40
What are some limitations with BMI?
does not represent body composition
-does not distinguish fat from muscles, bones
does not consider waist size
-abdominal fat a good predictor of health problems
was not intended for individual assessment
inaccuracies for certain populations
-older adults, those who are ill, pregnancy, ethnicities, growing children/adolescents
What is waist circumference associated with?
WC is strongly associated with CV and all-cause mortality, particularly when adjusting for BMI
Differentiate low, high, and very high risk waist circumference.
low risk:
- < 37 in (94 cm) for men, < 31.5 in (80 cm) for women
high risk:
- > 37 in (94 cm) for men, > 31.5 in (80 cm) for women
very high risk:
- > 40.2 in (102 cm) for men, > 34.6 in (88 cm) for women
Is BMI an accurate tool for identifying adiposity-related complications?
although BMI is widely used to assess and classify obesity, it is not an accurate tool for identifying adiposity-related complications
What is preclinical obesity?
a condition of excess adiposity without current organ dysfunction or limitations in daily activities but with increased future health risk
Why are we concerned about obesity?
excess adipose tissue is associated with increased morbidity and mortality
complications of obesity:
-T2DM
-cancers (colon, kidney, esophagus, endometrium, breast)
-gout
-gallbladder disease
-NAFLD
What is the goal of obesity treatment?
multifactorial
-rather than simply weight loss
What are the risk factors for obesity?
lower SES
genetic predisposition
highly processed diet
physical inactivity
disordered/insufficient sleep
stress
depression, some eating disorders, other mental health conditions
medications
childhood obesity
gut microbiota ?
Differentiate diabetes medications based on impact on weight.
weight loss:
-SGLT2 inhibitors, GLP1RAs
weight neutral:
-DPP4 inhibitors, acarbose, metformin
weight gain:
-insulin, SUs, meglitinides, TZDs
Is obesity a chronic disease?
Obesity Canada Guidelines:
-obesity is a chronic disease characterized by the presence of excessive and/or dysfunctional adipose tissue that impairs health and wellbeing
WHO, AMA, and CMA recognize obesity as a chronic disease
What should the diagnosis of obesity be based on?
the presence of functional, medical, +/or psychosocial impairments related to the presence of abnormal or excess body fat rather than anthropometric measures alone
Is obesity recognized as a chronic disease by governments?
no official recognition
-no coverage for medications
What are the management options for obesity?
lifestyle (dietary, physical activity, CBT)
pharmacotherapy
bariatric surgery
Will most patients meet their obesity management goals with behavioral changes alone?
most will not
-behavioral: ~1-5% wt loss
-behavioral + pharmacotherapy: ~20-40% wt loss
-behavioral + surgery: ~20-40%
What is the best way to reduce caloric intake?
there is no one best fit for everyone
What happens to most people who calorie restrict?
return to baseline weight within 1-2 yrs
-calorie restriction on its own shown not to be sustainable long-term
Why is calorie restriction not sustainable in the long-term?
not due to willpower, but rather strong biological mechanisms that protect the body against weight loss
What must occur for weight loss to occur with dietary restriction?
caloric expenditure must be greater than caloric intake
Which diet is the best for weight loss?
they must be patient-specific
-refer to dietitian
focus on changes that will improve health, not just weight changes
What are the recommendations for physical activity in order to promote weight loss?
aerobic exercise:
-goal of 30-60 min of moderate to vigorous aerobic activity on most days (> 150 mins/week)
resistance training
decrease sedentary time
What are the benefits of physical activity?
regulary physical activity can improve cardiometabolic risk factors and QoL, mood, body image
-benefits are partly independent of weight loss
resistance training:
-may promote weight maintenance
-increase muscle mass
Describe CBT for weight loss.
medically supervised programs are that are interdisciplinary are best (few and far between)
can be individual or group sessions
involves goal-setting, problem-solving, developing confidence and overcoming barriers
What are the obesity pharmacotherapy options?
orlistat
GLP1RAs
naltrexone/bupropion
What is the indication for the obesity pharmacotherapy options?
indicated for chronic weight management if BMI > 30 kg/m2 or > 27 kg/m2 if co-morbidities associated with excess body fat (i.e. T2DM, HTN, dyslipidemia)
-should be in conjunction with health behavior changes
What is the MOA of orlistat?
reversible lipase inhibitor in the GIT
-lipases hydrolyze dietary fats, converting them to monoglycerides and triglycerides
-inhibits dietary fat absorption by approximately 30%
-as a result, increased fecal fat excretion
How should orlistat be taken?
take with, or up to 1h after, each meal
skip a meal (or meal has no fat), skip a dose
What kind of diet should a patient on orlistat be following?
follow a mildly hypocaloric diet with < 30% calories from fat
What are the adverse effects of orlistat?
orlistat is not significantly absorbed; most AEs are GI
-flatulence (sometimes with discharge)
-loose, oily stools
-fecal urgency/incontinence
-abdominal discomfort
What are the contraindications of orlistat?
malabsorption syndromes
cholestasis
What are precautions for use of orlistat?
GI and hepatic disorders
What are the drug interactions of orlistat?
separate multivitamin by at least 2 hours
-reduces absorption of fat-soluble vitamins (ADEK)
decreased vit K absorption can increase anticoagulation with warfarin
may decrease absorption of cyclosporine, levothyroxine, antiepileptics, and antiretrovirals
-separate dosing times by 3-4 hours
What is the MOA of naltrexone/bupropion?
naltrexone: opioid receptor antagonist
-prevents beta endorphin-mediate pro-opiomelanocortin autoregulation (works in the brain)
bupropion: inhibits reuptake of DA and NE
-increases DA in the mesolimbic pathway
help induce satiety and decreases cravings via actions in the brain
-i.e. less cravings and less appetite lead to less food intake
How is naltrexone/bupropion dosed?
slow titration targeting maintenance dose of 2 tabs BID
-follow dosing instructions to minimize seizure risk and AE
How should naltrexone/bupropion be taken?
avoid taking with high fat meals
True or false: naltrexone/bupropion tablets can be split
false
How should the efficacy of naltrexone/bupropion be evaluated?
at week 12 of full dose, if >5% weight loss not achieved, a response is unlikely
What are the common adverse effects of bupropion/naltrexone?
NVD
constipation
headache
dizziness
dry mouth
insomnia
What are the rare adverse effects of bupropion/naltrexone?
seizure
worsening depression
What are some monitoring parameters for bupropion/naltrexone?
BP
HR
suicidal thoughts
What are contraindications of bupropion/naltrexone?
opioid use
uncontrolled HTN
history of or risk factors for seizures
bulimia/anorexia
What are the drug interactions of bupropion/naltrexone?
bupropion a strong 2D6 inhibitor (dose adjust)
-SSRIs, TCA, BBs, antipsychotics, antiarrhythmics
bupropion metabolized by 2B6
-clopidogrel, cyclophosphamide, ticlopidine
-less effect when used with inducers (ritonavir, CBZ)
MAOIs
-do not use within 14 days (hypertensive reactions)
high fat meal increases systemic absorption
What are the major incretins?
GLP-1 and GIP
What are incretins?
hormones secreted from the gut in response to food which then stimulates insulin secretion
What is the MOA of drugs that mimic incretins?
enhance satiety, decrease appetite, delay gastric emptying, decrease glucagon, and increase insulin
What is the weight loss indication for liraglutide?
adults:
-BMI > 30 or > 27 with at least one weight-related comorbidity
12-18 yo:
-inadequate response to diet/exercise & body weight > 60 kg & an initial BMI > 30 kg/m2
How is liraglutide dosed?
start at 0.6 mg SC daily
-increase by 0.6 mg weekly until 3 mg daily
Where is liraglutide injected?
abdomen
thigh
upper arm
How do we evaluate the efficacy of liraglutide for weight loss?
if weight loss is not > 5% by week 12, a response is unlikely
What are the common adverse effects of liraglutide?
NVD
What are the rare adverse effects of liraglutide?
acute chronic pancreatitis
cholestasis
monitor BG and signs/sx of pancreatitis
What is a contraindication to liraglutide?
personal history of thyroid cancer
What is the weight loss indication for semaglutide in adults?
adults patients with an initial BMI of
-30 kg/m2 or greater (obesity) or
-27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbidity such as HTN, T2DM, DLD, or OSA
What is the weight loss indication for semaglutide in pediatrics?
patients aged 12 to less than 18 years:
-with an initial BMI at the 95th percentile or greater for age and sex, and
-a body weight above 60 kg (132 lbs), and
-an inadequate response to reduced calorie diet and physical activity alone
What are the adverse effects and contraindications for semaglutide?
similar to liraglutide
How is semaglutide dosed?
starting dose: 0.25 mg/week
-gradually increase every 4 weeks
target dose: 2.4 mg/week
Describe the SELECT trial.
semaglutide 2.4 mg vs placebo to see if it reduces MACE in those with overweight/obesity and CVD (without diabetes)
the primary outcome, composite of CV death, nonfatal MI, and nonfatal stroke, for semaglutide vs placebo was 6.5% vs 8.0%
additional outcomes:
-HbA1c > 6.5%: 3.5% vs 12.0%
-change in systolic BP: -3.8 vs -0.5 mmHg
-mean change in BW at 104 wks: -9.4% vs -0.9%
Describe the STEP-HFpEF trial.
semaglutide 2.4 mg for 52 wks in those with HFpEF, obesity, and no diabetes showed significant improvement in HF-related symptoms
Describe the FLOW trial.
patients with diabetes and CKD received 1 mg semaglutide weekly or placebo
the risk of a primary-outcome event was 24% lower in the semaglutide group
Do GLP1RAs increase the risk of self-harm/suicide?
Health Canada review found no evidence of increased risk
What are some other agents that dont have an indication for weight loss but may cause some weight loss?
bupropion
fluoxetine
topiramate
methylphenidate
SGLT2i
metformin
What happens when weight loss interventions are discontinued?
weight will start to increase
-a long-term treatment plan is required
-patients and clinicians tend to focus on short-term interventions to manage obesity
When should we stop obesity pharmacotherapy?
if > 5% wt loss not achieved after 3 mo on full/maximum tolerated dose
-what was the patients previous weight trajectory?
-what factors could be impeding weight loss efforts?
-consider trying a different medication if no other evident etiologies of lack of success are apparent
pharmacotherapy is intended to be part of a long-term treatment strategy
True or false: obesity pharmacotherapy is commonly prescribed to eligible patients
false
only 2% of eligible patients for obesity pharmacotherapy received it
What is the MOA of tirzepatide?
GIP and GLP1 receptor agonist
-promotes satiety, weight loss, insulin secretion, decreased glucagon, and insulin sensitivity
What is the indication for tirzepatide?
FDA approved for weight loss (Zepbound)
-adults with BMI > 30 kg/m2 or > 27 kg/m2 with at least 1 weight-related condition
Canada: only indicated for adults with T2DM (Mounjaro)
How is tirzepatide titrated?
dose is increased over 4-20 weeks to achieve a weekly dose of 5,10, or 15 mg
What is the effect of the dose of tirzepatide on weight?
dose-dependent effect
What were the results of the SURMOUNT 1 trial?
average weight reduction 15 mg: -20.9% (48 lbs) from 108 kg mean initial weight
nearly 40% lost > 25% TBW
When is bariatric surgery considered?
those with BMI > 35
What are the benefits of bariatric surgery?
can lead to sustainable weight loss
20-45% weight loss
-also reduces morbidity and mortality of associated conditions
has the best outcomes on patients with respect to QoL, long-term weight loss, and resolution of obesity-related dx
What are some take home points regarding obesity pharmacotherapy?
not all medications work for everyone
-individual responses widely vary but they do work for some
after max effect is seen, weight loss will plateau
if med is d/c, wt gain is to be expected
expectations & monitoring: wt loss should be > 5% within 3 months of maintenance dose
5-10% wt loss may decrease risk factors for CVD
wt loss goals should be realistic
