Obesity Flashcards
How many Canadians are impacted by obesity?
26% of Canadian adults had a BMI over 30 (obese)
34% of Canadian adults are considered overweight (BMI between 25 and 30)
1/3 Canadian children have a BMI over 25
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)
What are some limitations associated with BMI?
Does not represent body composition (fat, muscle, and bones all contribute to weight equally)
Does not consider waist size (abdominal fat is a good predictor for health problems)
Inaccuracies in certain populations (elderly, ill patients, pregnancy, ethnicities, and growing children)
Why is body fat location important?
Body fat located at the waist is associated with more medical conditions (DM, CV)
Body fat located in the hips and thighs are lower risk
Waist circumference is strongly associated with CV and all-cause mortality, particularly when adjusting for BMI
What is preclinical obesity?
A condition of excess adiposity without current organ dysfunction or limitations in daily activities but with increased future health risk (can develop into clinical obesity)
What are some risk factors associated with obesity?
- Lower socioeconomic status
- Genetic predisposition
- Highly processed diet
- Physical inactivity
- Disordered/insufficient sleep
- Stress
- Depression, some eating disorders, other mental health conditions (may cause weight gain)
- Medications (ex. olanzapine, see slide 13)
- Childhood obesity (remain obese into adulthood)
- Gut microbiota
What is the cognitive link for obesity?
The relationship between weight gain, nutrition, and the brain is very complex
- The hypothalamus helps regulate energy intake and expenditure (when activated, it stimulates hunger sensation)
- The mesolimbic provides the emotional, pleasurable, rewarding aspects of eating (smells, sights, and emotions signal a desire to eat)
- The cognitive lobe helps one control adverse situations (such as nocturnal overeating)
What are the three primary methods by which obesity can be managed?
- Lifestyle (dietary, physical activity, CBT)
- Pharmacotherapy
- Bariatric surgery
Why are dietary interventions not as successful for weight loss?
Caloric restriction on its own is not sustainable long-term. It is not due to willpower, but rather strong biological mechanisms that protect the body against weight loss
What are some physical activity approaches to help control obesity?
Regular physical activity can improve cardiometabolic risk factors and QOL, mood, body image (benefits are partly independent of weight loss)
Aerobic exercise (30-60min of mod-vigorous aerobic activity 3-4 days per week)
Resistance training (promotes weight maintenance and increase muscle mass)
Decrease sedentary time
What are the main pharmacotherapeutic options for obesity?
Orlistat
Liraglutide
Naltrexone/bupropion
Semaglutide 2.4mg
They are indicated in patients with a BMI over 30 if co-morbidities like T2DM, HTN, or high cholesterol can be attributed to weight.
What is the mechanism of action for orlistat?
It is a reversibe lipase inhibitor in the GI tract.
Orlistat inhibits dietary fat absorption by 30% (increased fecal fat excretion)
When should orlistat be administered?
Take with, or up to 1 hour after each meal
If the patient skips a meal, skip a dose
Is orlistat as effective in patients on a vegan diet vs. those who eat meat?
No, orlistat is less effective in patients who are already on a low fat diet due to its MOA
What are some adverse effects associated with orlistat?
Not systemically absorbed significantly
Most ADRs are GI:
- Flatulence
- Loose, oily stools
- Fecal urgency/incontinence
- Abdominal discomfort
What are some contraindications to orlistat use?
Malabsorption syndromes
Cholestasis
What are some precautions for orlistat use?
GI and hepatic disorders
What are some drug interactions associated with orlistat?
Separate from fat-soluble vitamins (A, D, E, and K)
Decreased vit K absorption can increase anticoagulation with warfarin
Decreased absorption of cyclosporine, levothyroxine, anti-epileptic and anti-retrovirals (separate dosing)
What is the MOA for naltrexone/bupropion (Contrave) in obesity?
Individually do not impact weight significantly, but the combo can cause significant weight reduction. Help induce satiety and decrease cravings via actions in the brain.
Naltrexone: opioid antagonist
Bupropion: Inhibits DA and NE uptake, increases DA in the mesolimbic
Should naltrexone/bupropion (Contrave) be taken with meals?
Avoid taking with high fat meals
Does naltrexone/bupropion (Contrave) need to be tapered to start?
Yes, it is tapered over 4 weeks
When should a trial of naltrexone/bupropion (Contrave) be stopped?
If at week 12, weight loss is less than 5%, then d/c trial as response is unlikely
What are some common adverse effects associated with naltrexone/bupropion (Contrave)?
Nausea, vomiting, constipation, diarrhea
Headaches, dry mouth dizziness, insomnia
What are some rare adverse effects associated with naltrexone/bupropion (Contrave)?
Seizure, worsening of depression (bupropion is CI if patient has seizures)
Monitor BP, HR, suicidal thoughts
What are some contraindications associated with naltrexone/bupropion (Contrave)?
Opioid use (CI with naltrexone)
Uncontrolled HTN
History of risk factors for seizures
Bulimia/anorexia
What are some drug interactions associated with naltrexone/bupropion (Contrave)?
Bupropion is a strong 2D6 inhibitor (SSRIs, TCAs, beta-blockers, antiarrhythmics)
Do not use MAOIs within 14 days (increased risk of hypertensive reactions)
What is the impact of a high fat meal on naltrexone/bupropion (Contrave) absorption?
High fat meal increases systemic absorption
What are incretins?
They are hormones secreted from the gut in response to food which then stimulates insulin secretion
2 major incretins: GLP-1 and GIP
What is the impact of GLP1 receptor activation?
Enhance satiety, decrease appetite, delay gastric emptying, decrease glucagon, and increase insulin
Review slides 39 and 40 for liraglutide
Review slide 41 for semaglutide indications in obesity
What are some common adverse effects associated with semaglutide?
Nausea (worse during the first 36 hours)
Vomiting
Diarrhea
What are some rare adverse effects associated with semaglutide?
Acute pancreatitis, cholelithiasis
Monitor BG and signs/symptoms of pancreatitis
What are some contraindications associated with semaglutide?
Personal history of thyroid cancers
What is the clinical benefit of semaglutide on weight loss?
Significant benefit with semaglutide
What were the outcomes of the SELECT Trial?
Reduces MACE in those with overweight/obesity and CVD (in patients without diabetes)
Review slide 47-49 for a review of weight loss drugs
What are some non-indicated drugs for weight loss?
Bupropion
Fluoxetine
Topiramate
Methylphenidate
SGLT2Is and Metformin
What is the impact of stopping drugs for obesity?
If an intervention is d/c, weight will start to increase (like other chronic conditions)
What is the unique MOA of Tirzepatide?
GIP and GLP1 receptor agonist
Review slide 55-58
What is the efficacy of tirzepatide?
Average weight reduction loss by 20% from mean initial weight
Review slides 60-61 for future obesity treatment agents
In which obese patients is bariatric surgery indicated?
Consider those with BMI over 35
What is the efficacy of bariatric surgery on obesity?
Success depends on appropriate patient selection, education, and follow-up
20-45% weight loss (can be sustainable)
Reduces morbidity and mortality of associated conditions (increased life expectancy)
What is the purpose of bariatric surgery?
Goal is to shorten GI tract and limit absorption of nutrients
What are some strategies by which children can maintain a healthy weight?
Healthy eating (eat together as a family)
Physical activity (60min of physical activity per day and limit sedentary activities)
Review slide 66 for take home points about obesity treatment
