GLP1 RAs
Glucagon-like Peptide (GLP)
● Glucagon-like Peptide (GLP) is a naturally occurring hormone secreted by the L cells in
the small intestine.
● GLP lowers blood glucose by:
○ Stimulating the production of insulin
○ Inhibiting glucagon secretions, which stimulates the release of glucose from the
liver.
● Does this via action on the pancreatic islet cells
GLP-1RA
● Glucagon-like Peptide 1 Receptor Agonists were originally developed to treat type II
diabetes.
● Weight loss as a result of treatment was observed and GLP-1RAs were then explored for
the treatment of the disease of obesity.
Impact of GLP-1RA Therapy
● GLP1-1RA therapy is extra effective, as it targets both the GI and reward system
mechanisms.
○ GI Impact
■ Reduce appetite
■ Reduce hunger
■ Slow transit time of food from the stomach
■ Increase fullness after eating
○ Reward System Impact on receptors in the hypothalamus
■ Reduces loss of control eating.
■ Reduces preference for high-fat foods.
○ The combined effects of both lead to reduced energy intake.
GLP1 Analogues
● GLP1s are hormone-mimicking medications.
● GLP1 analogues include:
○ Liraglutide (2010)
○ Dulaglutide (2014)
○ Semaglutide (2017) = Olympic + Wegoby
GLP1 Analogues - Semaglutide
● Semaglutide has 94% similar structure to native human GLP.
● Considered the newest generation of GLP-1 RAs.
● Better rates of weight loss observed than previous generation GLP-1 RAs (i.e. liraglutide
or dulaglutide)
● Longer half-life of 1 week, therefore increasing ease of use for consumers.
○ A longer half-life allows an injection one time per week (which helps with better
compliance and better health outcomes).
Chemical Modifications
● Three chemical modifications were made to extend half-life, including.
○ 1. Make it less susceptible to degradation.
○ 2. Increase strength and specific binding to albumin.
○ 3. Prevention of binding at the wrong site - making it more specific.
■ Better at binding to right receptors.
○ Half life extended to 1 week.
■ Therefore the client only has to inject 1 x per week.
■ The goal was to improve client compliance and quality of life.
■ Previous first-generation GLP-1RAs required once or twice daily dosing.
GLP1 RAs Examples
● Seeing weight loss with the use of medication initially used for type II diabetes led to the
development of the drug specifically for weight loss.
● Ozempic, a medication for type II diabetes, is taken and marketed for weight loss.
● For weight loss purposes, the dosage is three times the amount for type II diabetes
● The annual average weight loss gradually increases with chemical modifications.
% of Weight Loss Needed for Improvement in Health
● As little as 5% of weight loss will improve biomarkers.
● So why are weight loss drugs trying to be modified to increase the % of weight loss?
○ The main focus is not really on health, but now on aesthetics and weight bias
(prioritizing skinny bodies).
Medications for Type II Diabetes
● Victoza (liraglutide)
● Trulicity (dulaglutide)
● Ozempic (semaglutide)
● Manjaro (tirzepatide)
Medications for Weight Loss
● Saxenda (liraglutide)
● Wegoby (semaglutide)
● Zep Bound (tirzepatide)
● TRIUMPH-2 Trial (retratrutide)
Tirzepatide vs. Retratrutide
● Tirzepatide includes 2 active ingredients that mimic two gut hormones instead of just one
- GLP-1 + glucose-dependent insulinotropic polypeptide (GIP) Receptor Agonist
● Retratrutide contains 3 active ingredients that target three hormone receptors - GLP-1,
GIP, plus glucagon.
Safety and Tolerability of GLP-1 RAs
● The most frequent adverse events (AE) reported are GI-related.
● Nausea, vomiting, diarrhea
○ 20-51% of patients (nonclinical trial clients with diabetes)
○ 23.1-48.4% of patients (clinical trial patients, with and without T2 diabetes)
● Adverse events appear to happen mostly during dose escalation.
● Reported to decrease over time
● 5.4-9.9% of clinical trial participants discontinued treatment due to AE.
STEP 1 Trial Extension - Design
● N=1960 subjects, BMI >/= 30
○ Part 1: 68 weeks 1 x weekly semaglutide injection @2.4 mg vs placebo
○ Part 2: After 68 weeks discontinued semaglutide
■ Observed weight and cardiometabolic factors over next 52 weeks.
STEP 1 Trial Extension - Results
● Participants regained ⅔ of weight loss in next 1 year ~5.6% below baseline
● Participants with greater weight loss had greater weight regain (eg, if they had lost 20%
or more of baseline body weight)
● Trail stopped at this point (52 weeks)
STEP 1 Trial Extension - Considerations
● Important to note that the trial stopped at 52 weeks in order to not report “bad” results.
● Rapid weight regain after rapid weight loss leads to weight gain (possibly even more than
baseline) and cardiometabolic factors worsen.
● This data is not reflected in the actual trial.
Long-Term Treatment and Considerations
● GLP-1 agonists are meant to be long-term and potentially lifelong weight-management
medications.
● Yet long-term adverse effects are still not known.
○ Risk of developing disordered eating/eating disorder?
○ No known research yet…can we extrapolate from other examples?
■ WLS examples?
■ Biggest losers examples?
■ Other weight loss medication examples?
■ Will the body correct itself differently after being on GLP-1 RAs than with
these examples?
Weight Loss Medications Developmental Timeline: 2000-2010
● 2000
○ Orlistat inhibits fat absorption.
● 2005
○ GLP-1RA - first given market approval.
● 2010
○ Phentermine and naltrexone.
■ Phentermine suppresses appetite.
■ Naltrexone, which is an opioid antagonist, suppresses appetite.
Weight Loss Medications Developmental Timeline: 2012
● 2012
○ Liraglutide: GLP-1RA
■ Reduces appetite and food cravings
■ Increases satiety
■ Alters food preference and reward pathways
○ Phentermine Topiramate (Topamax)
■ Anti-epileptic
■ Suppresses appetite
Weight Loss Medications Developmental Timeline: 2015
● 2015
○ Semaglutide: GLP-1RA
■ Reduces appetite and food cravings
■ Increases satiety
■ Alters food preference and reward pathways
■ Greater weight loss seen vs other GLP-1 RAs
■ Chemical modifications increase half life to 1 week
Weight Loss Medications Developmental Timeline: 2024+
● 2024+
○ Multiple combinations of active ingredients
■ Tirezepatide with GLP-1RAs + GIP
■ Relatrutide with GLP-1 RAs + GIP + glucagon
ARFID/OSFED
Avoidant/Restrictive Food Intake Disorder (ARFID)
1. Disinterested in eating.
2. Avoiding food of certain colors and shapes.
3. And/or concern about the aversive consequences of eating.
a. Typically interpreted as a response to a previous traumatic event (i.e., choking).
b. Or an aversive experience, eg. repeated vomiting (50%)
ARFID DSM-5 Criteria
1. Significant weight loss (failure to meet expected weight gain and/or faltering growth in
children).
2. Significant nutritional deficiencies.
3. Dependence on enteral nutrition or oral nutrition supplements.
4. Marked interference on psychosocial functioning.
ARFID - Details
● More common in children and young adolescents, and less common in late adolescence
and adulthood.
● Often associated with psychiatric co-morbidity, especially with anxious and
obsessive-compulsive features.
● More than just “picky eating,” children do NOT grow out of it, and often become
malnourished because of the limited variety of food they will eat.
ARFID - Prevalence
● The true prevalence of ARFID is still being studied, but preliminary estimates suggest it
may affect as many as 5% of children.
● Boys may have a higher risk for ARFID than girls.
● No body image concerns.
ARFID and Co-occurring Disorders
● The same study found
○ 30% have a mood disorder
○ 75% have an anxiety disorder
○ ~20% have an autism spectrum condition
Brain Deterioration with Restriction
● Even without body image concerns, malnutrition from a lack of food will lead to a
malnourished brain with ARFID.
● A malnourished child increases anxiety, depression, increases rigidity of thoughts,
increases obsessive thoughts, and increases rumination (thoughts).
Malnutrition and Obsessive Thoughts
● How much of your day do you spend thinking about food, calories, and body image?
○ AN: >100%
○ BE/BN: 80%
○ DE: 50%
○ Non-Ed: 15%
DSM-5 Criteria for ARFID
● An individual must meet all the current DSM-5 criteria to be diagnosed with ARFID.
○ Criteria A
○ Criteria B
○ Criteria C
○ Criteria D
DSM-5 Criteria for ARFID - Criteria A
● An eating or feeding disturbance (eg. apparent lack of interest in eating or food;
avoidance of eating based on the sensory characteristics of food; concern about adverse
consequences of eating) as manifested by persistent failure to meet appropriate nutrition
and/or energy needs associated with one (or more) of the following:
○ 1. Significant weight loss (or failure to achieve expected weight gain or faltering
growth in children).
○ 2. Significant nutritional deficiencies.
○ 3. Dependence on enteral feeding or oral nutrition supplements.
○ 4. Marked interference with psychological functioning.
DSM-5 Criteria for ARFID - Criteria B
● The disturbance is not better explained by a lack of available food or by an associated
culturally sanctioned practice.
DSM-5 Criteria for ARFID - Criteria C
● The disturbance does not occur exclusively during anorexia or bulimia nervosa, and is not
associated with disturbance in the way the weight or body shape is experienced.
● The eating disturbance does not occur exclusively during the course of anorexia nervosa
or bulimia nervosa, and there is no evidence of a disturbance in the way in which one’s
body weight or shape is experienced.
DSM-5 Criteria for ARFID - Criteria D
● The eating disturbance is not attributable to a concurrent medical condition or not better
explained by another mental disorder. When the eating disturbance occurs in the context
of another condition or disorder, the severity of the eating disturbance exceeds that
routinely associated with the condition or disorder and warrants additional clinical
attention.
Characteristics of ARFID
● Disinterest in food
○ Avoiding certain colors and shapes
○ Concern about choking or vomiting
○ Concern about weight loss and/or body image?
Orthorexia
● Focus on food quality
● Unrealistic food beliefs
● Desire to maximize health
● Flaunt behaviors
● Intrusive thoughts
● Ritualized food preparation
● Focus on contamination
Orthorexia - Overlap
● Overlap with anorexia
○ Limited insight
○ Guilt over food transgressions
○ Ego-syntonic thoughts
○ Perfectionism
○ Cognitive rigidity
● Overlap with ARFID
○ No drive for thinness
○ No concern with body weight or shape
Anorexia
● Focus on food quantity
● Fear of obesity, disturbed body image
● Drive for thinness; excessive exercising
ARFID
● Food quality and quantity are irrelevant
● Lack of interest in food due to sensory characteristics
● Fear of adverse consequences of eating (vomiting, choking)
ARFID - Overlap
● Overlap with Orthorexia
○ No drive for thinness
○ No concern with body weight or shape
● Overlap with Anorexia
○ Depressed mood
Anorexia, Orthorexia, and ARFID Overlap
● Weight loss
● Selective in the foods eaten
● Avoidance of certain foods
● Nutritional deficiencies
● Impaired functioning
● Trait anxiety
ARFID Risks
● ARFID is a risk factor for AN.
● Orthorexia and ARFID put a client at risk of developing AN if untreated, and they
progress.
Treating ARFID
1. Treat Malnutrition - Restore weight if appropriate
2. Exposure and response prevention therapy (ERP) for “unsafe” foods (OCD) protocol
3. Medication as necessary for anxiety (SRRIs)
4. Therapy
a. Behavioral therapy essential: CBT for rigidity, black and white thinking (DBT and
ACT are hepful and under the umbrella of CBT)
b. Psychotherapy to examine the importance of this way of eating \
Treatment Interventions: Nutrition
● Nourishment and weight restoration (supplements if needed).
● Assess for food allergies
● Hierarchy of foods ("safer foods first")
○ Can be difficult, as fear against food can vary.
○ Will need different sets of hierachies
● Hierarchy of meaning of foods
● Education on foods and nutrition
● Refer to speech pathologist, PCP, GI as needed
● Exposure and Response Prevention Therapy (ERP)
Exposure and Response Prevention Therapy (ERP)
● Food Chaining: Helps introduce new foods while building on the client’s past succssful
eating experience
● Flavor Mapping
○ Identifying food the client is comfortable with eating amd then trying that food in
a different form
■ For example, the client likes yogurt and peach.. Maybe try a peach yogurt
● Transitional Foods
○ Finding transitional food to meet the goal food
● Flavor Masking
○ Using different condiments to get over flavor
Progress in ARFID Treatment (1)
● Client expanded the variety of food and increased meal completion, supporting the client
in weight stabilization and maintaining biologically appropriate weight consistently prior
to discharge.
● Client grew several inches and was back on the growth curve.
● Client was able to practice skills both in and out of the program to regulate anxiety.
Progress in ARFID Treatment (2)
● Client was able to go to the grocery store each week with parents and choose her own
ERP foods and integrate ERPs in and out of the program.
● Clients used DBT distress tolerance self soothing techniques in group therapy to support
with attention and focus.
● Client was able to increase ADLs in home and decrease oppositional behavior to support
a positive behavior modification plan.
● Client was able to return to school and meet with guidance counselors and school nurses
daily.
Other Specified Feeding or Eating Disorder (OSFED)
● People with OSFED have symptoms that are similar to one or more other eating
disorders, but are not exactly the same.
● Other eating disorders include anorexia nervosa, bulimia nervosa, and binge eating
disorder.
● It is an "umbrella term" for behaviors that don't meet other criteria.
OSFED Presentation Examples
● BED, BN, and AN
○ The client has these presentations but may not meet the full criteria.
● OSFED being "not as bad" is a myth. Even if someone does not meet the full criteria of
traditional ED, their symptoms can still cause great distress, psychological damage, and a
decrease in QOL.
● Harmful as practitioners to have belief that OSFED is less severe
Questions
1) Where is GLP-1 primarily secreted from?
A) Pancreatic beta cells
B) Hypothalamus
C) Small intestine
D) Liver
2) Which of the following is not an effect of GLP-1?
A) Stimulates insulin release
B) Increases glucagon secretion
C) Suppresses appetite
D) Slows gastric emptying
3) GLP-1 receptor agonists primarily target which cells?
A) Alpha cells
B) Beta cells
C) Neurons
D) Parietal cells
4) GLP-1 RAs were originally developed to treat:
A) Obesity
B) Type I diabetes
C) Type II diabetes
D) Hyperthyroidism
5) Which secondary benefit was observed in GLP-1 RA users?
A) Reduced inflammation
B) Weight loss
C) Muscle gain
D) Improved mood
6) GLP-1 RAs affect appetite by:
A) Increasing hunger hormones
B) Suppressing leptin
C) Reducing dopamine
D) Acting on the hypothalamus
7) GLP-1 RAs delay:
A) Saliva production
B) Intestinal absorption
C) Gastric emptying
D) Glucagon secretion
8) GLP-1 RAs reduce brain reward responses to:
A) Sweet and fatty foods
B) Alcohol
C) Salty snacks
D) Exercise
9) Which of the following is reduced by GLP-1 RA therapy?
A) Desire for vegetables
B) Craving for high-fat foods
C) Salt appetite
D) Fruit sugar preference
10)GLP-1 RAs target which two systems?
A) Immune and circulatory
B) Metabolic and endocrine
C) Gastrointestinal and central nervous system
D) Muscular and skeletal
11)Which of the following was the first GLP-1 analogue?
A) Exenatide
B) Semaglutide
C) Dulaglutide
D) Tirzepatide
12)Dulaglutide was approved in:
A) 2008
B) 2010
C) 2014
D) 2018
13)Semaglutide is marketed under which names?
A) Ozempic and Wegovy
B) Saxenda and Rybelsus
C) Trulicity and Mounjaro
D) Victoza and Zepbound
14)Semaglutide is what percent similar to native GLP?
A) 50%
B) 74%
C) 89%
D) 94%
15)The long half-life of semaglutide allows for:
A) Daily injections
B) Monthly infusions
C) Once-weekly dosing
D) Constant infusion pumps
16)What was the purpose of modifying GLP-1 into longer-acting forms?
A) Increase potency
B) Decrease cost
C) Extend the duration of action
D) Reduce receptor binding
17)How often is semaglutide injected for most indications?
A) Daily
B) Weekly
C) Monthly
D) Twice a day
18)Which shows greater weight loss: liraglutide or semaglutide?
A) Liraglutide
B) Semaglutide
C) Both equal
D) Unknown
19)Weekly dosing is beneficial because:
A) It reduces bioavailability
B) It increases costs
C) It improves adherence
D) It enhances fasting glucose spikes
20)Which medication is sold under the name Victoza?
A) Dulaglutide
B) Semaglutide
C) Liraglutide
D) Tirzepatide
21)Trulicity is the brand name for:
A) Exenatide
B) Dulaglutide
C) Semaglutide
D) Tirzepatide
22)Which semaglutide-based drug is indicated for obesity treatment?
A) Ozempic
B) Victoza
C) Trulicity
D) Wegovy
23)Mounjaro is marketed for which condition?
A) Weight loss
B) Diabetes
C) GERD
D) Hypertension
24)Retratrutide targets how many hormone receptors?
A) One
B) Two
C) Three
D) Four
25)What is the key difference between tirzepatide and retratrutide?
A) Chemical structure
B) Number of receptor targets
C) Injection method
D) Half-life
26)Which of the following is a GLP-1 RA approved for weight loss?
A) Ozempic
B) Trulicity
C) Wegovy
D) Victoza
27)Weight loss dose of semaglutide is approximately:
A) 0.5x diabetes dose
B) Same as diabetes dose
C) 2x diabetes dose
D) 3x diabetes dose
28)Tirzepatide acts on which two receptors?
A) GLP-1 and leptin
B) GLP-1 and GIP
C) GLP-1 and glucagon
D) GLP-1 and insulin
29)Which trial evaluated retratrutide for weight loss?
A) STEP 1
B) SELECT
C) SURMOUNT-1
D) EASE
30)Most common adverse events of GLP-1 RAs are:
A) Neurological symptoms
B) GI symptoms
C) Skin rashes
D) Headaches
31) When do adverse events with GLP-1 RAs mostly occur?
A) During dose maintenance
B) After one year
C) During dose escalation
D) After food intake
32)Discontinuation rate due to AEs in trials is around:
A) 3%
B) 10%
C) 18%
D) 30%
33)Duration of semaglutide treatment in STEP 1 trial:
A) 12 weeks
B) 36 weeks
C) 68 weeks
D) 96 weeks
34)BMI requirement for STEP 1 trial participants:
A) ≥25
B) ≥27
C) ≥30
D) ≥35
35)Percent of weight regained in STEP 1 extension after stopping drug:
A) 5%
B) 11.6%
C) 20%
D) 28%
36)The STEP 1 extension trial raised concern due to:
A) Liver failure
B) High dropout rate
C) Rapid weight regain
D) Unblinded design
37)Rapid weight regain is linked to worsened:
A) Bone density
B) Sleep quality
C) Cardiometabolic health
D) Skin elasticity
38)A key unknown in long-term GLP-1 RA use is:
A) Pancreatic cancer
B) Addiction
C) Disordered eating risk
D) Kidney stones
39)Current data on long-term disordered eating and GLP-1 use is:
A) Well established
B) Inconclusive
C) Strongly negative
D) Nonexistent
40)ARFID typically develops due to:
A) Desire for thinness
B) Cultural diet pressure
C) A traumatic food-related event
D) Compulsive exercise
41)How does ARFID differ from picky eating?
A) It is outgrown naturally
B) It leads to significant impairment
C) It involves calorie counting
D) It starts in adolescence
42)What percentage of ARFID patients have anxiety disorders?
A) 15%
B) 30%
C) 50%
D) 75%
43)Which is a diagnostic criterion for ARFID?
A) Purging
B) Excessive exercise
C) Nutritional deficiency
D) Fear of fatness
44)Criterion C rules out ARFID when:
A) There is an allergy
B) The behavior is due to a body image concern
C) A sibling has an eating disorder
D) BMI is normal
45)ARFID differs from anorexia because it lacks:
A) Dietary restriction
B) Body image disturbance
C) Fear of eating
D) Nutrient deficiency
46)Fear of choking or vomiting during eating is common in:
A) Bulimia nervosa
B) ARFID
C) Binge eating disorder
D) Orthorexia
47)Orthorexia is characterized by:
A) Obsession with thinness
B) Overeating
C) Preoccupation with healthy food
D) Avoiding social situations
48)Food chaining in ARFID treatment involves:
A) Replacing fear foods
B) Linking preferred foods to new foods
C) Removing all fear foods
D) Counting calories
49)What do orthorexia, anorexia, and ARFID have in common?
A) Fear of weight gain
B) Focus on muscle mass
C) Avoidance of certain foods
D) Compulsive eating
