Weight Management

GI PTPM
Erin Tersegno, PharmD
Capital Cardiology Associates | ACPHS
February 2024
 2

Objectives
1. Summarize weight gain/obesity trends and implications of obesity on overall health
status

2. Identify medications that can contribute to weight gain

3. Memorize classifications for overweight and obesity based on BMI

4. Outline treatment goals for weight loss

5. Describe types of bariatric surgery and medication-related considerations for post-

surgical patients

6. Employ an individualized pharmacotherapy recommendation for weight management

Background
 Classification of Overweight and Obesity 4

Obesity is a chronic relapsing progressive disease defined by abnormal or excessive

adiposity that may impair health

• Body Mass Index (BMI) is a measure of weight in

relation to height BMI =
• When interpretating BMI: use clinical judgement -
edema, high muscularity, muscle wasting, etc.

Underweight Healthy Weight Overweight Obesity Class 1 Obesity Class 2 Obesity Class 3
BMI <18.5 BMI: 18.5-24.9 BMI: 25-29.9 BMI: 30-34.9 BMI: 35-39.9 BMI: ≥40
Individualizing Weight Loss. AACE. 2020.
 BMI Calculation Example
Patient weighs 206 lbs and is 5’7’’
2.2 lb = 1 kg
• 5 feet = 60 inches 2.54 inches = 1 cm
• 5’7’’ = 67 inches 100 cm = 1 m

• 67 inches X2.54 = 170 cm 206 lbs / 2.2 lbs =93.6 kg

• 170 cm = 1.70 m
• 1.702 = 2.89 m2

93.6 kg / 2.89 m2 = BMI = 32.4 kg/m2 = Obesity class 1

Underweight Healthy Weight Overweight Obesity Class 1 Obesity Class 2 Obesity Class 3
BMI <18.5 BMI: 18.5-24.9 BMI: 25-29.9 BMI: 30-34.9 BMI: 35-39.9 BMI: ≥40
Waist Circumference (WC) Utility 6

• WC is a measurement of abdominal
body fats
• Strong correlation between overall
and abdominal obesity
• Underdiagnosis of cardiovascular
disease (CVD) risk in patients who
have excess fat, but not obesity per
BMI
• Use WC: Unmask CVD risk in
individuals with “normal” weight

Increases in BMI, abdominal obesity linked to higher risk for male breast cancer. Healio News. 27 June
2022.
Garvey WT, Mechanick JI, Brett EM, et al. Comprehensive Clinical Practice Guidelines for Medical
Care of Patient with Obesity. AACE/ACE Guidelines. July 2016;22(2)
Healthy Weight, Nutrition, and Physical Activity: Assessing your weight. CDC. 3 June 2022.
Waist Circumference (WC) Utility 7

South Asian,
Gender U.S. and Canada Southeast Asian,
and East Asian
Men ≥102 cm ≥ 85 cm

Women ≥ 88 cm ≥ 74 cm

Increases in BMI, abdominal obesity linked to higher risk for male breast cancer. Healio News. 27 June
2022.
Garvey WT, Mechanick JI, Brett EM, et al. Comprehensive Clinical Practice Guidelines for Medical
Care of Patient with Obesity. AACE/ACE Guidelines. July 2016;22(2)
Healthy Weight, Nutrition, and Physical Activity: Assessing your weight. CDC. 3 June 2022.
Why Do We Treat Obesity? Obesity Effects on Cardiovascular Disease

VTE
Overweight and Obesity
Globally HTN
2.8-3.5 billion people

Annual Medical CAD Stroke

Costs
Nearly $173 billion in
2019 dollars in the
Powell-Wiley TM, Poirier P, Burke LE, et al. Obesity and cardiovascular disease: a scientific
Unites States statement from the American heart association. 22 April 2021;143:e989-e1010
Garvey WT, Mechanick JI, Brett EM, et al. Comprehensive Clinical Practice Guidelines for Medical
Care of Patient with Obesity. AACE/ACE Guidelines. July 2016;22(2)
Section 2: Why Do We Treat Obesity. American Association of Clinical Endocrinology.
Adult Obesity Facts. CDC.
Benefits of Weight Loss

Many Benefits! To name a few…

• Lower cancer risk
• Improved mobility, reduced joint pain, increased physical activity tolerance
• Reduced symptoms of bladder incontinence, obstructive sleep apnea, acid reflux
• Reduction in hyperlipidemia, hypertension

Garvey WT, Mechanick JI, Brett EM, et al. Comprehensive Clinical Practice Guidelines Obesity and Cancer. NIH National Cancer Institute. 5 April 2022.
for Medical Care of Patient with Obesity. AACE/ACE Guidelines. July 2016;22(2)
OVERVIEW OF WEIGHT LOSS

~60-70% of Americans try to lose

weight each year

Only a small percentage can achieve

goals and maintain weight loss

Individualizing Weight Loss Therapy. American Association of Clinical Endocrinology.

SlidesGo
 GENERAL THERAPEUTIC
GOALS
AHA/ACC/TOS
5-10% loss over 6 months

NHLBI
10% loss over 6 months

CDC
1-2 pounds per week

Garvey WT, Mechanick JI, Brett EM, et al. AACE/ACE Comprehensive Clinical Practice Guidelines for medical care of patients with obesity. Endocr Pract. 2016;3:1–203.
Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS Guideline for the Management of overweight and Obesity in adults. Circulation. 2014;129(suppl 2):S102–S138.
SlidesGo.
American Association of Clinical Endocrinologist (AACE) and American College of
Endocrinology (ACE) Guidelines Weight Loss Goals
Clinical Co-morbidity Weight-loss Goals Clinical Goals – Improve In
Depression Uncertain ∙ Depression scores
∙ Symptoms
Dyslipidemia ≥5-15% ∙ HDL
∙ Reduce non-HDL and TG
Hypertension ≥5-15% ∙ Reduction in blood pressure
∙ Reduction in doses/amount of medications
Metabolic Syndrome 10% ∙ Prevention of type 2 diabetes
Non-Alcoholic Fatty Liver Steatosis: ≥5% ∙ Steatosis: intrahepatocellular lipid
Disease Steatohepatitis: 10-40% ∙ Steatohepatitis: inflammation and fibrosis

Obstructive Sleep Apnea ≥7-11% ∙ Symptoms

∙ Apnea-hypo-apnea index
Osteoarthritis ≥10% ∙ Symptoms
∙ Increase function
Pre-Diabetes 10% ∙ Prevention of type 2 diabetes
Type 2 Diabetes ≥5-15% ∙ Hemoglobin A1C
∙ Reduce doses and amount medications

Garvey WT, Mechanick JI, Brett EM, et al. Comprehensive Clinical Practice Guidelines for Medical Care of Patient with Obesity. AACE/ACE Guidelines. July 2016;22(2)
Weight Management –
Lifestyle Approach
Approach to Weight Management
Multiple pieces to the puzzle

Cardiac Rehab Co-Morbid Diet

Behavior
Diseases

Alcohol
Surgery Medications Exercise Consumption

Garvey WT, Mechanick JI, Brett EM, et al. Comprehensive Clinical Practice Guidelines for Medical Individualizing Weight Loss Therapy. American Association of Clinical Endocrinology.
Care of Patient with Obesity. AACE/ACE Guidelines. July 2016;22(2) SlidesGo
 Low Calorie Diets

1200-1500 kcal/day 1500-1800 kcal/day

WOMEN MEN
Obesity Algorithm®. © 2021 Obesity Medicine Association
Federal Caloric Restriction Diets:
Federal Guidelines: Mediterranean Diet
• 10-35% protein, 45-65% carbohydrates Recommended by the AACE guidelines for
20-30% fats medical care of patients with obesity

Consume: One of best studied approaches for

 <10% calories/day from added sugars cardiovascular health
and saturated fats
 <2300 mg/day of sodium What to Eat?
-High-fiber grains (whole grains, fruits,
vegetables, nuts)
Alcohol consumption: -Fish and seafood
• 1 drink/day: women -Extra virgin olive oil
• 2 drinks/day: men

Comprehensive Clinical Practice Guidelines for Medical Care of Patient Individualizing Weight Loss Therapy. American Association of Clinical Endocrinology.
with Obesity. AACE/ACE Guidelines. July 2016;22(2)
 Physical Activity

Aerobic activity: goal of > 150 min/week of

moderate exercise over 3 – 5 daily
sessions/week

Resistance/muscle training: goal >2 days per

week

SlidesGo
The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. NHI NHLBI. October 2000.
 Physical Activity
GOAL: 150 minutes/week
Examples of Moderate Physical
Activity
Washing windows or floors for 45-60 mins

Gardening for 30-45 minutes

Wheeling self in wheelchair for 30-40 minutes

Walking 2 miles in 30 min

Stair walking for 15 mins

Water aerobics for 30 minutes

Bicycling 5 miles in 30 minutes
SlidesGo
The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. NHI NHLBI. October 2000.
Non-Exercise Activity Thermogenesis
(NEAT)
• NEAT = Energy expended in a day beyond
purposeful exercise
• Important component of total daily energy
expenditure (TDEE)
• TDEE = how many calories burned per day

DeFeo S. Stretches and Exercises for Computer Users. SportsRec. 8 July 2011.
Villablanca PA, Alegria JR, Mookadam, et al. Nonexercise Activity Thermogenesis in Obesity
Management. Mayo Clin Proc. April 2015;90(4):509-519.
Individualizing Weight Loss Therapy. American Association of Clinical Endocrinology.
Non-Exercise Activity Thermogenesis (NEAT)

NEAT Physical NEAT ACTIVITIES

Activity Stand up every 30 minutes while
working
Standing desk/Arm circles
TDEE
Basal Park far away from the store
Thermic
Stretch/move around while
Metabolic Effect of
watching TV or cooking
Rate Food

Villablanca PA, Alegria JR, Mookadam, et al. Nonexercise Activity Thermogenesis in

Obesity Management. Mayo Clin Proc. April 2015;90(4):509-519.
Weight Management –
Surgical Approach
 Candidates: Bariatric Surgery:
 Gastric bypass
 BMI ≥40 kg/m2 or
Surgical Intervention (commonly known as
Roux-en-Y gastric bypass
 BMI ≥35 kg/m2 (RYGB))
with a co-morbid  Biliopancreatic diversion
condition (e.g., (BPD-DS)
T2DM, HTN, HLD)  Laparoscopic sleeve
gastrectomy (LSG)
Recognized as the  Laparoscopic gastric
most effective banding (LAGB)
modality to reduce
body weight and
obesity-related Weight loss and post-
diseases as well as surgical morbidity:
mortality. BPD-DS and
RYGB>LSG>LAGB
Comprehensive Clinical Practice Guidelines for Medical Care of Patient SlidesGo
with Obesity. AACE/ACE Guidelines. July 2016;22(2)
Bariatric Surgery
RYGB LSG BPD-DS

Procedure: creation of a small Procedure: removal of the Procedure: sleeve

gastric pouch followed by lateral portion of the stomach gastrectomy followed by
procedure to bypass a section to create a long gastric pouch procedure to bypass a large
of the small intestine or sleeve portion of the small intestine

Mechanism: primarily Mechanism: primarily Mechanism: restrictive and

restrictive but with restrictive malabsorptive
malabsorptive component

Roux-En-Y Gastric Bypass. University of Illinois Hospital and Health Sciences System. 2023.
Nat Rev Gastroenterol Hepatol. 2017 Mar;14(3):160-169.
BPD-DS Weight Loss Surgery. URMC. 2023.
Sleeve Gastrectomy. Bringham and Womens Hospital. 2023.
Clinical Pharmacist Role – Surgical Approach
Examples:

Pre-Surgery Recommendations:
• Stop oral contraception before surgery to reduce the risk of venous
thromboembolism
• Stop metformin or SGLT2i prior to surgical procedures to minimize risk
of lactic acidosis and euglycemic ketoacidosis
Post-Surgery Recommendation:
• Stop extended-release formulations
• Provide counseling on medication changes
• Recommend laboratory monitoring
Clements JN, Albanese NP, D’Souza JJ, et al. Clinical review and
role of clinical pharmacists in obesity management. J Am Coll
Clin Pharm. 2021;4:1469-1484.
Weight Management -
Pharmacotherapy
Approach
Pharmacotherapy Treatment Step-Wise
Approach
1 Screen for pharmacotherapy candidates

Complete medication reconciliation and

2 evaluate weight-related complications

3 Assess readiness for weight management

4 Discuss pharmacotherapy options

 Candidates: Remember:
 BMI ≥30 kg/m2 or 1 Criteria
for  Medications may not
work on their own
 BMI ≥27 kg/m2 with Pharmacotherapy  Always as an adjunct
an obesity related to an energy-deficit
meal plan, increased
medical condition
physical activity and
(e.g., HTN, HLD, T2DM)
behavior modification.
 Medications amplify
Use clinical
interpretation of BMI effects of behavioral
changes to produce
consumption of fewer
calories

Garvey WT, Mechanick JI, Brett EM, et al. Comprehensive Clinical Practice Why medical weight loss might be your answer.
Guidelines for Medical Care of Patient with Obesity. AACE/ACE Guidelines. July Generations family practice. 2022.
2016;22(2)
 Weight Related Diseases or Complications

Metabolic syndrome
Type 2 diabetes or pre-diabetes
Dyslipidemia
Hypertension
Cardiovascular disease
Nonalcoholic fatty liver disease
Polycystic ovary syndrome
Female infertility
Male hypogonadism
Obstructive sleep apnea
Asthma/reactive airway disease
Osteoarthritis
Urinary stress incontinence
Gastroesophageal reflux disease
Depression

Garvey WT, Mechanick JI, Brett EM, et al. AACE/ACE Comprehensive Clinical Practice Guidelines for medical care of patients with obesity. Endocr Pract. 2016;3:1–203.
Pharmacotherapy Treatment Step-Wise
Approach
1 Screen for pharmacotherapy candidates

Complete medication reconciliation and

2 evaluate weight-related complications

3 Assess readiness for weight management

4 Discuss pharmacotherapy options

 Please note not ALL medications under

2 Examples: Prescription Drug-induced Weight Gain these drug classes can induce weight gain.
For example: a diabetes medication,
Jardiance or metformin will NOT induce
weight gain.

✔ Anti-Depressants –TCA (amitriptyline, doxepin, nortriptyline), SSRIs

(paroxetine>sertraline, citalopram)
Anticholinergics
Anticonvulsants
Antihistamines ✔ Anti-Seizure – valproic acid, carbamazepine, gabapentin, pregabalin
Antipsychotics
Antiretrovirals ✔ Atypical Antipsychotics – olanzapine>clozapine>risperidone>aripiprazole
Beta-Blockers
✔ Beta-Blockers – older agents (metoprolol, propranolol, atenolol) > newer
Contraceptives
Glucocorticoids
agents (nebivolol, carvedilol)
Insulin
SSRIs
✔ Diabetic Medications – sulfonylureas, thiazolidinediones, insulin
Thiazolidinediones
TCAs
✔ Corticosteroids – prednisone, cortisone
Clements JN, Albanese NP, D’Souza JJ, et al. Clinical review and
role of clinical pharmacists in obesity management. J Am Coll
Clin Pharm. 2021;4:1469-1484.
✔ Oral Contraceptives – progestin only > combination
2 Assess Weight-Related
Complications

Diabete
• Consider when determining optimal
s
pharmacotherapy
Asthma • Motivation

Depressi • Weight loss goals

on
• May require additional screening or
CV
Disease referrals
Pharmacotherapy Treatment Step-Wise
Approach
1 Screen for pharmacotherapy candidates

Complete medication reconciliation and

2 evaluate weight-related complications

3 Assess readiness for weight management

4 Discuss pharmacotherapy options

3 Assess Readiness to Lose Weight

Has the individual sought weight loss on their own initiative?

What are the individuals stress level and mood?

Does the individual have a eating or mood disorder?

How much weight does the individual expect to lose?

The Practical Guide: Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. NHI NHLBI. October 2000.
Pharmacotherapy Treatment Step-Wise
Approach
1 Screen for pharmacotherapy candidates

Complete medication reconciliation and

2 evaluate weight-related complications

3 Assess readiness for weight management

4 Discuss pharmacotherapy options

 4 Pharmacotherapy Options

0
01 02 04
3

GLP-1 Agonists Antidepressant/ Lipase Inhibitor CNS Stimulant

Liraglutide Opioid Antagonist
Semaglutide
Bupropion/Naltrexone Orlistat Phentermine/
Tirzepatide *
Topiramate
Phentermine
*= GLP-1 and GIP agonist
Glucagon-like Peptide-1 Activity

↓ Food Intake ↑ Insulin ↓ Gastric

↑ Satiety ↓ Glucagon emptying
 Glucagon-like-peptide-1 (GLP-1) Agonists
Liraglutide (Saxenda)
Semaglutide (Wegovy)

Mechanism Warnings
Synthetic analog of human GLP, ↑ -Pancreatitis
incretin levels, reduced gastric emptying -Gallbladder disease
-Gastroparesis

Causes Contraindications
Increased satiety -Medullary thyroid cancer
Feel fuller sooner -Multiple endocrine neoplasia syndrome
-Pregnancy
GLP-1 Agonist Contraindications
● Medullary thyroid cancer?
○ Risk with personal OR family history
○ Rodent models

● Multiple Endocrine Neoplasia Syndrome

○ Genetic disorder

● Pregnancy – Examples:
○ Shown to be teratogenic in rats at or above 0.8 times systemic exposures in
obese humans from the maximum recommended dose 3 mg/day (liraglutide)
○ Discontinue WEGOVY at least 2 months before a planned pregnancy

Kannan S, Nasr C. Should we be concern about thyroid cancer in patients taking GLP-1 receptor agonist?. Semaglutide. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc.
Cleveland Clinic Journal of Medicine. March 2015;82(3) 2014 [updated 4 Aug 2022].
Saxenda. Package insert. Novo Nordisk December 2014.
GLP-1 Agonist Side Effects
Most Common Side effects: Gastrointestinal (GI)
• Constipation, nausea, vomiting, diarrhea, abdominal pain,
dyspepsia

Other Side Effects:

• Increased heart rate
• Injection site reactions
• May cause hypoglycemia when used with other antidiabetic
medications
 Liraglutide
(Saxenda)
FDA Approval
2014

Class: Dose Titration

GLP-1 Agonist Once daily (QD) subcutaneous injection;
titrate weekly by 0.6 mg as tolerated
0.6 mg QD →
Literature Review: 1.2 mg QD →
SCALE Trial: 2015; 56 weeks 1.8 mg QD →
• Average (Avg) weight loss: 8.0±6.7% 2.4 mg QD →
• Avg 8.4 kg loss 3.0 mg QD (maintenance dose)

LEADER Trial: 2016; 3.8 years

Reduced risk of composite cardiovascular (CV)
Liraglutide. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc.; [updated 4 Aug 2022].
death, nonfatal myocardial infarction (MI), and Marso SP, Daniels GH, Brown-Frandsen K, et al. A Randomized, Liraglutide and Cardiovascular Outcomes in Type 2
Diabetes. N Eng J Med. 28 July 2016;375:311-322.
nonfatal stroke in patients with T2DM Pi-Sunyer X, Astrup A, Fujioka K, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight
Management. N Eng J Med. 2 July 2015;373: 11-22.
Obesity- Saxenda. Novomedlink. May 2021.
 Semaglutide
(Wegovy)
FDA Approval
2021

Class: Dose Titration

GLP-1 Agonist Once weekly (QW) subcutaneous injection;
titrate every 4 weeks as tolerated
0.25 mg QW →
Literature Review: 0.5mg QW→
1 mg QW→
STEP-1 Trial: 2021; 68 weeks
1.7 mg QW →
• Avg Weight Loss: 14.9 – 16.9 %
2.4 mg QW (maintenance dose)
• Avg 15.3 kg loss
SUSTAIN-6 Trial: 2016; 2 years
Reduced risk of CV death, nonfatal MI, and nonfatal stroke
in patients with T2DM Semaglutide. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc.; 2014 [updated 4 Aug 2022].
SELECT Trial; 2023; 39 +/- 9.4 months Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Eng J Med. 18 March 2021;384:
989-1002
Lincoff AM, et al. Semaglutide and CV Outcomes in Obesity without Diabetes. N Engl J Med. 2023; 389: 2221-2232
Reduced risk of CV death, nonfatal MI, or nonfatal stroke in Marso SP, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 10
November 2016;375:1834-1844
patients without T2DM Wegovy – List Price. NovoCare. March 2022..
STEP-1 Trial: Wegovy

Primary End Points

INCLUSION:
-Percentage change in body
- BMI≥ 30 kg/m2
Randomized, weight
- BMI≥ 27 kg/m2 +
Double-blind, ≥ 1 weight-
-Weight reduction of 5% or more
Placebo related Exclusion: Diabetes
controlled complication
68
Weeks
Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Eng J Med. 18 March 2021;384: 989-1002
 STEP-1 Trial: Wegovy; Baseline
Characteristics
Characteristic Semaglutide Placebo
(n=1306) (n=655)
Mean Body weight 105.4 ± 22.1 105.2 ± 21.5
(kg)
Mean BMI 37.8 ± 6.7 38.0 ± 6.5

Pre-DM (%) 45.4 40.2

Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Eng J Med. 18 March 2021;384: 989-1002.
 STEP-1 Trial: Mean change in
Weight Assessed at week 68

Semaglutide 2.4 mg PCB

Treatment Policy - 14.9 % - 2.4 %

Trial Product - 16.9 % - 2.4 %

Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Eng J Med. 18 March 2021;384: 989-1002.
STEP-1 Trial: Mean change in Weight
Weight loss observed at week 4 until week 60 (nadir)

Semaglutide 2.4 mg PCB

Treatment Policy- - 14.9 % - 2.4 %
Estimand

Trial Product- - 16.9 % - 2.4 %

Estimand

Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Eng J Med. 18 March 2021;384: 989-1002.
 STEP-1 Trial: Safety Data
• Most frequent ADE: Gastrointestinal (GI) disorders (nausea, diarrhea,
vomiting, and constipation)
• Semaglutide: 74.2% vs. Placebo: 47.9%
• Mild-to-moderate in severity
• Transient
• Resolved without permanent discontinuation of the regimen

• Gallbladder-related disorders (cholelithiasis)

• Semaglutide: 2.6% vs. Placebo: 1.2%

• Mild, Acute Pancreatitis: number of events

• Semaglutide: 3 vs. Placebo: 0
Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults
with Overweight or Obesity. N Eng J Med. 18 March 2021;384: 989-1002
 GLP-1 and GIP Agonist
Tirzepatide (Zepbound)

Mechanism Warnings
-Pancreatitis
Mimics both GLP-1 and GIP -Gallbladder disease
-Gastroparesis

Causes Contraindications
Increased satiety -Medullary thyroid cancer
Feel fuller sooner -Multiple endocrine neoplasia syndrome
-Pregnancy
 GLP-1 and GIP Activity

GLP-1 GLP-1 GLP-1

↓ Food Intake ↑ Insulin ↓ Gastric
↑ Satiety ↓ Glucagon emptying

GIP GIP GIP

↓ Food Intake ↑ Insulin ↓ Gastric acid
Seino Y, Fukushima M, Yabe D. GIP and GLP-1, the two incretin
↑ Insulin Sensitivity secretion
hormones: Similarities and differences. J Diabetes Investig. April
2010;1(1-2):8-23. ↑ Glucagon
 Tirzepatide (Zepbound)
FDA Approval
November 2023

Dose Titration
Class:
Once weekly (QW) subcutaneous injection;
GLP-1/GIP Agonist titrate every 4 weeks as tolerated
2.5 mg QW →
5 mg QW →
Literature Review: 7.5 mg QW 
10 mg QW →
SURMOUNT Trial: 2022; 72 weeks
• Weight loss trial; excluded patients with 12.5 mg QW →
diabetes 15 mg QW
• Avg Weight Loss: 16 - 22.5%
• Avg 16 – 24 kg loss
SURMOUNT
Trial
Safety Results

Jastreboff AM, Aronne LJ, Ahmad

NN, et al. Tirzepatide Once
Weekly for the Treatment of
Obesity. N Eng J Med. 21 July
2022;387:205-216
 SURMOUNT-1 Trial:
Zepbound and CV Benefit?
Benefits were noted with respect to changes in:

• Waist circumference
• Systolic and diastolic blood pressure
• Pre-DM status
• Lipid levels
• Decrease in LDL
• Decrease in total cholesterol
• Increase in HDL

Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of
Obesity. N Eng J Med. 21 July 2022;387:205-216
Clinical Pearls – Saxenda, Wegovy, Zepbound
Patient concerned with GI side effects
• GI ADE most common during dose escalation
• GI ADE may subside with continued therapy

Patient administered first increased dose now has severe nausea

• Consider delaying dose escalation; taper to discontinue not required

Patient forgot to administer their dose this week Never double up

on doses!
• Saxenda: Missed dose >3 days: re-initiate at 0.6 mg
• Wegovy: Missed dose >2 days from regular schedule: skip dose, take next scheduled injection
• Zepbound: Missed dose >4 days from regular schedule: skip dose, take next scheduled injection
GLP-1 and GLP-1/GIP Agonists Comparison
Liraglutide(Saxenda) Semaglutide (Wegovy) Trizepatide (Zepbound)
Literature •Avg Weight Loss: 8% •Avg Weight Loss: 14.9 – 16.9 % •Avg Weight Loss: 16- 22.5 %
Weight Loss •8.4 kg loss •15.3 kg loss •16-24 kg loss

Dose Daily SQ injection; titrate weekly by 0.6 Once weekly SQ injection; titrate every Once weekly SQ injection; titrate every
mg as tolerated 4 weeks as tolerated 4 weeks as tolerated
0.6 mg →1.2 mg →1.8 mg →2.4 mg → 0.25 mg → 0.5mg →1 mg→ 1.7 mg → 2.5 mg → 5mg →7.5 mg→ 10 mg →
3.0 mg (maintenance) 2.4 mg (maintenance) 12.5 mg 
15 mg

Side Effects GI: nausea, vomiting, constipation, abdominal pain, diarrhea; slow dose titration is key to minimize ADE
Rare: pancreatitis, cholelithiasis
Contraindications: MTC (personal or family history), MEN2 (personal history), pregnancy
Notes Pro: Con:
• Efficacy in variety of populations (including T2DM) • GI ADE
• Composite CV risk reduction • Saxenda- once daily injection versus once weekly

Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and Cardiovascular Outcome in Type 2 Diabetes. N Eng J
Med. 28 July 2016;375:311-322.
 4 Pharmacotherapy Options

0
01 02 04
3

GLP-1 Agonists Antidepressant/ Lipase Inhibitor CNS Stimulant

Liraglutide Opioid Antagonist
Semaglutide
Bupropion/Naltrexone Orlistat Phentermine/
Tirzepatide *
Topiramate
Phentermine
*= GLP-1 and GIP agonist
 Bupropion/Naltrexone (Contrave)
FDA Approval
2014

Class:
-Anorexiant; dopamine-norepinephrine reuptake inhibitor (bupropion) and opioid antagonist (naltrexone)

Mechanism:
-Exact neurochemical mechanism not fully understood
-Reduces appetite and enhances satiety secondary to synergy in the hypothalamus and the mesolimbic dopamine circuit

Notes
-Strong 2D6 inhibitor
-Do not take with high fat meals
Contrave. Package insert. Takeda Pharmaceuticals. 2014.
Sherman MM, Ungureanu S, Rey JA. Naltrexone/Bupropion ER (Contrave): Newly Approved
1 Contrave Tablet = 8 mg naltrexone + 90 mg bupropion Treatment Option for Chronic Weight Management in Obese Adults. P T. 2016 Mar;41(3):164-72.
 Bupropion/Naltrexone (Contrave)
Dose Titration

Week 1: One tablet once in the morning

Week 2: One tablet twice daily administered in the

morning and evening
Weight Loss Data
Week 3: Two tablets in the morning and one tablet
• Avg weight loss of 3.7 – 8.1% from baseline in the evening
weight
Week 4: Two tablets twice daily administered in
• Avg loss of 4.9 kg relative to placebo the morning and in the evening (maintenance)

Sherman MM, Ungureanu S, Rey JA. Naltrexone/Bupropion ER (Contrave): Newly Approved Treatment Lancet. 2010 Aug 21;376(9741):595-605. | JAMA. 2015 Mar 24-31;313(12):1213-4.
Option for Chronic Weight Management in Obese Adults. P T. 2016 Mar;41(3):164-72. Contrave. 2023 Haymarket Media, Inc.
 Bupropion/Naltrexone (Contrave) Safety

• Nausea • Blood pressure (HTN) • Avoid in patients with

• Very common (~30%) • Heart Rate (tachycardia) uncontrolled hypertension
• Constipation (~20%) • Suicidal thoughts and • Avoid with current or history:
• Headache behaviors (boxed warning) seizure disorders, anorexia or
• Sleep disorder bulimia nervosa, or undergoing
• Vomiting abrupt discontinuation of
alcohol, benzos, and other
• Dry mouth
antiepileptic drugs
• Drug-drug interactions
• Opioids

Monitoring
Side Effects Contraindications
Parameters

Contrave. Package insert. Takeda Pharmaceuticals. 2014.

Contrave. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc. [updated 1 Feb 2023].
 Orlistat (Xenical [Rx] or Alli [OTC])
FDA Approval
1999

Class:
-Pancreatic and gastric lipase inhibitor; resulting fat malabsorption reduces net energy intake

Mechanism:
-Selectively inhibits the action of gastrointestinal lipases to reduce dietary fat absorption

Notes
-Large molecule that is not well absorbed – inhibits absorption of fats
-Recommend standard multivitamin (include vitamins A, D, E, K)

Orlistat. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc. [updated 20 Jan 2023].
Garvey WT, Mechanick JI, Brett EM, et al. Comprehensive Clinical Practice Guidelines for Medical Care of
Patient with Obesity. AACE/ACE Guidelines. July 2016;22(2).
 Orlistat (Xenical [Rx] or Alli [OTC])

Dosing

Rx: 120 mg three times daily before meals

Weight Loss Data OTC: 60 mg three times daily before meals

*take up to 1 hour before each fat-containing meal

XENDOS: 1997-2002; Avg weight loss
-1 yr: 4%
-4 yrs: 2-3%
Orlistat 120 mg PO TID: Avg loss of 3.4 kg relative to placebo
Xenical . Cheplapharm.
Orlistat 60 mg PO TID: Avg loss of 2.5 kg relative to placebo Alli. SimplyMeds Online Pharmacy.
Torgerson JS, Hauptman J, Boldrin MN, et al. XENical in the Prevention of Diabetes in Obese Subjects (XENDOS) Stud.
Diabetes Care 1. January 2004;27(1):155–161.
Garvey WT, Mechanick JI, Brett EM, et al. Comprehensive Clinical Practice Guidelines for Medical Care of Patient with
Obesity. AACE/ACE Guidelines. July 2016;22(2).
 Orlistat Safety

• Flatulence • Cholelithiasis • May impair absorption of

• Fecal Incontinence • Nephrolithiasis lipophilic drugs:
• Oily spotting • Cyclosporine
• Frequent bowel movements • Levothyroxine
• Abdominal pain • Multivitamins including A, D,
E, and/or K

Monitoring
Side Effects Drug Interactions
Parameters
 Phentermine and Topiramate (Qsymia) -
FDA Approval CIV
2012

Class:
-Anorexiant; Sympathomimetic amine; Norepinephrine-releasing agent (phentermine)
-Anticonvulsant; GABA receptor modulation (topiramate)

Mechanism:
-Reduced appetite secondary to CNS effects, including stimulation of the hypothalamus to release catecholamines

Weight Loss Data

-Avg loss: 5.1-10.9 % from baseline weight
-Phentermine 7.5 mg/topiramate 46 mg: Avg loss of 6.7 kg relative to placebo
-Phentermine 15 mg/topiramate 92 mg: Avg loss of 8.9 kg relative to placebo
Qsymia. Package insert. Vivus, Inc. July 2012.
Qsymia. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc. [updated 1 Feb 2023].
 Phentermine and Topiramate (Qsymia) - CIV
Dose Titration

Evaluate: ≥3% loss

Start: Increase to: Increase to: Evaluate: ≥5%
baseline weight.
Qsymia loss baseline
If not:
3.75/23mg 7.5/46 mg 15/92 mg weight.
D/C or ↑ to
once daily once daily once daily If not:
11.25/69 mg
x 14 days x 12 weeks x 12 weeks D/C therapy
once daily
X 14 days gradually

Qsymia 3.75 mg /23 mg = Phentermine 3.75 mg/topiramate 23 mg

Qsymia 7.5 mg /46 mg = Phentermine 7.5 mg/topiramate 46 mg
Qsymia 11.25 mg /69 mg = Phentermine 11.25 mg/topiramate 69 mg
Qsymia 15mg /92 mg = Phentermine 15 mg/topiramate 92 mg
D/C = discontinue; ↑ = increase
 Phentermine and Topiramate (Qsymia)
Safety
• Dry mouth • Blood pressure (HTN) • Glaucoma
• Insomnia • Heart Rate (tachycardia) • CIV: Risk of dependence
• Cognitive effects • CNS: delirium, mania, • Pregnancy - REMS Program:
• Constipation psychosis, insomnia and due to teratogenicity
• Dysgeusia anxiety
• Creatinine
• Increased risk of suicidal
ideation (topiramate)

Monitoring
Side Effects Contraindications
Parameters
 Phentermine (Adipex-P, Lomaira) - CIV
FDA Approval
1959- Only approved for short term – 12 weeks

Class:
-Anorexiant; Sympathomimetic amine; Norepinephrine-releasing agent (phentermine)

Weight Loss Data

-Magnitude of increased weight loss versus placebo: Only a fraction of a pound a week

Safety:
Cardiac and CNS effects
CI: heart disease, uncontrolled HTN, history of addiction or drug use
Tolerance and abuse risk

Phentermine. In: Lexi-drugs online [database on the Internet]. Hudson (OH): Lexicomp, Inc. [updated 3 Feb 2023].
Phentermine. Teva Pharmaceuticals. 2021..
Percent Weight Loss - Pharmacotherapy
Medication Maximum Reported Average
Weight Loss (%)

Orlistat 4
Bupropion + Naltrexone 3.7 - 8.1
Phentermine + Topiramate 5.1 – 10.9
Liraglutide 8.0 ± 6.7
Semaglutide 14.9 - 16.9
Tirzepatide 16 - 22.5
 Weight Loss Goals per Medication Utilized
AHA/ACC/TOS
5-10% loss over 6 months

Medication Duration of Therapy Weight-loss Goals

Liraglutide (Saxenda) 3 mg 4 months ≥4%

Semaglutide (Wegovy) 2.4 mg 5 months ≥5%

Bupropion and Naltrexone (Contrave) 3 months ≥5%

Phentermine and Topiramate (Qsymia) 3 months 7.5/46 mg: ≥3%

15/92 mg: ≥ 5 %

Garvey WT, Mechanick JI, Brett EM, et al. Comprehensive Clinical Practice Guidelines for Medical Care of Patient with Obesity. AACE/ACE Guidelines. July 2016;22(2)
How long can patients take the medication?
Medication Time
Phentermine 3 months
Orlistat 6 months
Phentermine + Topiramate 1 year
Bupropion + Naltrexone 1 year
Tirzepatide 1.4 years
Semaglutide 2 years
Liraglutide 3 years

Kushner RF, Calanna S, Davies M, et al. Semaglutide 2.4 mg for the Treatment of Obesity: Key
Elements of the STEP Trials 1 to 5. Obesity. 22 May 2020; 28(6):1050-1060.
 Safe
Weight Loss Medications and Co-existing Condition Caution
Avoid
Co-Existing Condition Saxenda Contrave Qsymia Orlistat
Wegovy
Zepbound
DM or pre-DM Substantial benefit Insufficient data for prevention
T2DM

HTN Monitor HR Monitor HR & BP Monitor HR

CI: uncontrolled HTN

CAD Monitor HR Monitor HR & BP Monitor HR

CHF Insufficient data Insufficient data Insufficient data Insufficient data

CKD: 30-49 MAX 8 mg/ 90 mg BID MAX 7.5 mg /46 mg QD

CKD <30 Clearance ↓ Clearance ↓ Ca oxalate stones

Hepatic Child-Pugh 5-9 Watch for cholelithiasis MAX 8 mg/ 90 mg QAM MAX 7.5 mg /46 mg QD Watch for cholelithiasis

Hepatic Child-Pugh >9

Depression/ Anxiety Insufficient safety data AVOID max dose: 15 mg /92 mg

QD
Avoid adolescents/ young adults w/
depression
Seizure Disorder Lowers seizure threshold If discontinue, taper slowly

Post-Bariatric Surgery Data available Insufficient data Limited data Insufficient data
COST CONCERNS

• Commercial insurances may cover Wegovy and Saxenda without a

prior authorization (PA)
• Co-payment cards available
• Medicare plans:
• Cannot cover medications marketed for weight loss
• Coverage with secondary plans may be possible
• May cover Ozempic or Mounjaro (T2DM/PA Required?)
Pharmacist Role
Ensure efficacy and safety of regimen chosen; collaborative practice
agreements; referral to bariatric surgeons, medical providers, dieticians,
etc.

Monitor progress of patients – ensure efficacy with continued use;

adequate dosing titration

Help patients manage side effects!

Ensure patients can obtain therapy - co-pay/coupon cards, manufacturer

patient assistance programs, letters of medical necessity
 Medication Pro and Cons

Liraglutide (Saxenda) Pro: DM benefit, Efficacy in a variety of populations, Composite CV risk reduction

Con: SQ injection, Daily injection, GI symptoms

Semaglutide (Wegovy) Pro: DM benefit, efficacy in a variety of populations, composite CV risk reduction
Con: SQ injection, GI symptoms
Tirzepatide (Zepbound) Pro: DM benefit, efficacy in a variety of populations, preliminary CV benefit,
greatest weight reduction
Con: SQ injection, GI symptoms
Bupropion/Naltrexone (Contrave) Pro: Oral tablet formulation
Con: Many warnings for screening, drug interactions
Orlistat (Xenical, Alli) Pro: Oral formulation
Con: Three times daily administration, GI side effects, drug interactions
Phentermine/Topiramate (Qsymia) Pro: Oral formulation
Con: CV and cognitive effects
Phentermine Pro: Oral formulation
Con: CV and cognitive effects, short term use only
 Medications in the Pipeline
Med Name Oral Semaglutide Injectable Retatrutide (LY3437943)
Literature •Avg Weight Loss: 15.1 % •Avg Weight Loss: 24.2%
Weight Loss With the 50 mg dose at 68 weeks of therapy With the 12 mg dose at 48 weeks of therapy
OASIS-1 Phase 3 Trial Phase 2 Trial

Dose Once daily oral tablet Once weekly SQ injection

3 mg, 7 mg, 14 mg, 25 mg, 50 mg 1 mg, 2 mg, 4 mg, 8 mg, 12 mg
(increase dose once every 4 weeks) (increase dose once every 4 weeks)

Side Effects GI: nausea, vomiting, constipation, diarrhea GI: nausea, vomiting, constipation, diarrhea
Typically transient and were mild-moderate in severity that Occurred primarily during dose escalation and were mild-moderate
resolved without permanent trial product discontinuation in severity, mitigated with started at lower doses
Mechanism of GLP-1 receptor agonist GIP, GLP-1, and GCG (G-protein coupled receptor for
Action glucagon) receptor agonist
More potent to GIP and less potent to GLP-1 and GCG

Notes Oral agent; not commercially available at the 50 mg Phase 2 data published only; not commercially available
dose

Jastreboff AM, et al. Triple-Hormone-Receptor Retatrutide for Obesity – a Phase 2 Trial. IN Engl J Med. 2023; 398: 514-526.
Knop FK, et al. OASIS 1: A Randomize, Double-Blind, Placebo-Controlled, Phase 3 Trial. Lancet. 2023; 402: 705-19.
 Thank You!

Erin Tersegno, PharmD

Capital Cardiology Associates | ACPHS

73