Anti-Obesity Medications in 2024:
What Do I Need To Know?
Sean M. O’Neill, MD, PhD
MSQC/ASPIRE Joint Meeting
April 12, 2024
maridebart cafraglutide
vs
Oatzempic
Sean M. O’Neill, MD, PhD
MSQC/ASPIRE Joint Meeting
April 12, 2024
Disclosures
None
Objective
As anesthesia providers and surgeons,
what do we absolutely need to know about anti-obesity medications
(mainly, GLP-1 receptor agonists) in 2024?
Objective
As anesthesia providers and surgeons,
what do we absolutely need to know about anti-obesity medications
(mainly, GLP-1 receptor agonists) in 2024?
You may have to cancel cases
Objective
As anesthesia providers and surgeons,
what do we absolutely need to know about anti-obesity medications
(mainly, GLP-1 receptor agonists) in 2024?
You may have to cancel cases
You may experience having your cases canceled
Objective
As anesthesia providers and surgeons,
what do we absolutely need to know about anti-obesity medications
(mainly, GLP-1 receptor agonists) in 2024?
You may have to cancel cases
You may experience having your cases canceled
This area is changing very rapidly, and will continue to do so
Outline
Fun Facts
Definitions
History of AOMs
Current Pharmacopeia
Effectiveness
Side Effects/Adverse Events
Usage
Implications for Anesthesia and Surgery
Outline
Fun Facts (and non-fact phenomena)
Definitions
History of AOMs
Current Pharmacopeia
Effectiveness
Side Effects/Adverse Events
Usage
Implications for Anesthesia and Surgery
2023
2024
>
396 B
>
Outline
Fun Facts (and non-fact phenomena)
Definitions
History of AOMs
Current Pharmacopeia
Effectiveness
Side Effects/Adverse Events
Usage
Implications for Anesthesia and Surgery
Anti-Obesity Medication (AOM)
FDA Indication is for:
Chronic weight management as an adjunct to diet and exercise if:
BMI > 30 kg/m^2
OR
BMI > 27 kg/m^2 & at least 1 weight-related comorbidity
Anti-Obesity Medication (AOM)
Minimum benchmark for approval:
Mean weight loss in treated group is >5% greater than placebo group
OR
>5% weight loss achieved in >35% of the treated population
(and double the rate of >5% weight loss in the placebo group)
AND
Cardiovascular safety trials
Outline
Fun Facts (and non-fact phenomena)
Definitions
History of AOMs
Current Pharmacopeia
Effectiveness
Side Effects/Adverse Events
Usage
Implications for Anesthesia and Surgery
AOM Timeline
1959: Phentermine, Diethylpropion
1960: Benzphetamine
1961: Phendimetrazine
1973: Fenfluramine (withdrawn 1998, pulmonary HTN)
1996: Dexfenfluramine (withdrawn 1998, pulmonary HTN)
1999: Orlistat
2012: Phentermine/Topiramate
2012: Lorcaserin (withdrawn 2020, increased risk of pancreatic, colon, lung CA)
2014: Naltrexone/Bupropion
2014: Liraglutide 3 mg SC
2021: Semaglutide 2.4 mg SC
(TBD): Tirzepatide 5/10/15 mg SC
Mechanism
Sympathomimetic / Appetite Suppression
AOM Timeline
1959: Phentermine, Diethylpropion
1960: Benzphetamine
1961: Phendimetrazine
1973: Fenfluramine
1996: Dexfenfluramine
1999: Orlistat
2012: Phentermine/Topiramate
2012: Lorcaserin (withdrawn 2020, increased risk of pancreatic, colon, lung CA)
2014: Naltrexone/Bupropion
2014: Liraglutide 3 mg SC
2021: Semaglutide 2.4 mg SC
(TBD): Tirzepatide 5/10/15 mg SC
Mechanism
Sympathomimetic / Appetite Suppression
Sympathomimetic / Appetite Suppression
AOM Timeline
1959: Phentermine, Diethylpropion
1960: Benzphetamine
1961: Phendimetrazine
1973: Fenfluramine
1996: Dexfenfluramine
1999: Orlistat
2012: Phentermine/Topiramate
2012: Lorcaserin (withdrawn 2020, increased risk of pancreatic, colon, lung CA)
2014: Naltrexone/Bupropion
2014: Liraglutide 3 mg SC
2021: Semaglutide 2.4 mg SC
(TBD): Tirzepatide 5/10/15 mg SC
Mechanism
Sympathomimetic / Appetite Suppression
(withdrawn 1998, pulmonary HTN)
(withdrawn 1998, pulmonary HTN)
AOM Timeline
1959: Phentermine, Diethylpropion
1960: Benzphetamine
1961: Phendimetrazine
1973: Fenfluramine
1996: Dexfenfluramine
1999: Orlistat
2012: Phentermine/Topiramate
2012: Lorcaserin (withdrawn 2020, increased risk of pancreatic, colon, lung CA)
2014: Naltrexone/Bupropion
2014: Liraglutide 3 mg SC
2021: Semaglutide 2.4 mg SC
(TBD): Tirzepatide 5/10/15 mg SC
Mechanism
Sympathomimetic / Appetite Suppression
Fat absorption (pancreatic lipase) inhibitor
AOM Timeline
1959: Phentermine, Diethylpropion
1960: Benzphetamine
1961: Phendimetrazine
1973: Fenfluramine
1996: Dexfenfluramine
1999: Orlistat
2012: Lorcaserin
2012: Phentermine/Topiramate
2014: Naltrexone/Bupropion
2014: Liraglutide 3 mg SC
2021: Semaglutide 2.4 mg SC
(TBD): Tirzepatide 5/10/15 mg SC
Mechanism
Sympathomimetic / Appetite Suppression
Fat absorption (pancreatic lipase) inhibitor
Serotonin R agonist (Hypothalamic POMC cells)
AOM Timeline
1959: Phentermine, Diethylpropion
1960: Benzphetamine
1961: Phendimetrazine
1973: Fenfluramine
1996: Dexfenfluramine
1999: Orlistat
2012: Lorcaserin
2012: Phentermine/Topiramate
2014: Naltrexone/Bupropion
2014: Liraglutide 3 mg SC
2021: Semaglutide 2.4 mg SC
(TBD): Tirzepatide 5/10/15 mg SC
Mechanism
Sympathomimetic / Appetite Suppression
Fat absorption (pancreatic lipase) inhibitor
(withdrawn 2020; panc, colon, lung CA risk)
AOM Timeline
1959: Phentermine, Diethylpropion
1960: Benzphetamine
1961: Phendimetrazine
1973: Fenfluramine
1996: Dexfenfluramine
1999: Orlistat
2012: Lorcaserin
2012: Phentermine/Topiramate
2014: Naltrexone/Bupropion
2014: Liraglutide 3 mg SC
2021: Semaglutide 2.4 mg SC
(TBD): Tirzepatide 5/10/15 mg SC
Mechanism
Sympathomimetic
Fat absorption (pancreatic lipase) inhibitor
Sympathomimetic + Appetite Suppressant
POMC ag, Opioid antag, Dopamine reup inhib
AOM Timeline
1959: Phentermine, Diethylpropion
1960: Benzphetamine
1961: Phendimetrazine
1973: Fenfluramine
1996: Dexfenfluramine
1999: Orlistat
2012: Lorcaserin
2012: Phentermine/Topiramate
2014: Naltrexone/Bupropion
2014: Liraglutide 3 mg SC
2021: Semaglutide 2.4 mg SC
(TBD): Tirzepatide 5/10/15 mg SC
Mechanism
Sympathomimetic
Fat absorption (pancreatic lipase) inhibitor
Sympathomimetic + Appetite Suppressant
POMC ag, Opioid antag, Dopamine reup inhib
Glucagon-like Peptide-1 (GLP-1) Rec Agonist
AOM Timeline
1959: Phentermine, Diethylpropion
1960: Benzphetamine
1961: Phendimetrazine
1973: Fenfluramine
1996: Dexfenfluramine
1999: Orlistat
2012: Lorcaserin
2012: Phentermine/Topiramate
2014: Naltrexone/Bupropion
2014: Liraglutide 3 mg SC
2021: Semaglutide 2.4 mg SC
2022: Tirzepatide 5/10/15 mg SC
Mechanism
Sympathomimetic
Fat absorption (pancreatic lipase) inhibitor
Sympathomimetic + Appetite Suppressant
POMC ag, Opioid antag, Dopamine reup inhib
Glucagon-like Peptide-1 (GLP-1) Rec Agonist
Glucagon-like Peptide-1 (GLP-1) Rec Agonist
GLP-1 Agonist + GIP Receptor Agonist
AOM Timeline
1959: Phentermine, Diethylpropion
1960: Benzphetamine
1961: Phendimetrazine
1973: Fenfluramine
1996: Dexfenfluramine
1999: Orlistat
2012: Lorcaserin
2012: Phentermine/Topiramate
2014: Naltrexone/Bupropion
2014: Liraglutide 3 mg SC
2021: Semaglutide 2.4 mg SC
2022: Tirzepatide 5/10/15 mg SC
(TBD): maridebart cafraglutide TBD mg SC
Mechanism
Sympathomimetic
Fat absorption (pancreatic lipase) inhibitor
Sympathomimetic + Appetite Suppressant
POMC ag, Opioid antag, Dopamine reup inhib
Glucagon-like Peptide-1 (GLP-1) Rec Agonist
Glucagon-like Peptide-1 (GLP-1) Rec Agonist
GLP-1 Agonist + GIP Receptor Agonist
GLP-1 Agonist + GIP Receptor Antagonist
Outline
Fun Facts (and non-fact phenomena)
Definitions
History of AOMs
Current Pharmacopeia
Mechanism/Dosing
Effectiveness
Side Effects/Adverse Events
Usage
Implications for Anesthesia and Surgery
AOMs: Current Pharmacopeia
1959: Phentermine, Diethylpropion
1960: Benzphetamine
1961: Phendimetrazine
1999: Orlistat
2012: Phentermine/Topiramate
2014: Naltrexone/Bupropion
2014: Liraglutide 3 mg SC
2021: Semaglutide 2.4 mg SC
2022: Tirzepatide 5/10/15 mg SC
Mechanism
Sympathomimetic
Pancreatic lipase inhibitor
Sympathomimetic + Appetite Supp
POMC ag, Opioid antag, Dopamine
GLP-1 RA
GLP-1 + GIP RA
GLP-1 RA
AOMs: Current Pharmacopeia
1959: Phentermine, Diethylpropion
1960: Benzphetamine
1961: Phendimetrazine
1999: Orlistat
2012: Phentermine/Topiramate
2014: Naltrexone/Bupropion
2014: Liraglutide 3 mg SC
2021: Semaglutide 2.4 mg SC
2022: Tirzepatide 5/10/15 mg SC
Trade Name
Adipex-P, Tenuate
Didrex
Bontrex, Adipost, Anorex,
Xenical
Qsymia
Contrave
Saxenda
Zepbound / Mounjaro
Wegovy
AOMs: Current Pharmacopeia
1959: Phentermine, Diethylpropion
1960: Benzphetamine
1961: Phendimetrazine
1999: Orlistat
2012: Phentermine/Topiramate
2014: Naltrexone/Bupropion
2014: Liraglutide 3 mg SC
2021: Semaglutide 2.4 mg SC
2022: Tirzepatide 5/10/15 mg SC
Mechanism
Sympathomimetic
Pancreatic lipase inhibitor
Sympathomimetic + Appetite Supp
POMC ag, Opioid antag, Dopamine
GLP-1 RA
GLP-1 + GIP RA
GLP-1 RA
GLP-1 RAs
Liraglutide
Semaglutide
Tirzepatide
GLP-1 RA
Drucker DJ. Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1.
Cell Metab. 2018 Apr 3;27(4):740-756.
GLP-1 RAs for T2DM (but also Obesity)
Liraglutide 3 mg SC daily
T2DM indication: liraglutide 1.2/1.8 mg SC daily (2010)
Semaglutide 2.4 mg SC weekly
T2DM indication: semaglutide 0.5/1/2 mg SC weekly (2017)
T2DM indication: semaglutide 3/7/14 mg PO daily (2019)
Tirzepatide 5/10/15 mg SC weekly*
T2DM indication: tirzepatide 5/10/15 mg SC weekly (2022)
GLP-1 RAs for T2DM (but also Obesity)
Liraglutide 3 mg SC daily Saxenda
T2DM indication: liraglutide 1.2/1.8 mg SC daily (2010) Victoza
Semaglutide 2.4 mg SC weekly Wegovy
T2DM indication: semaglutide 0.5/1/2 mg SC weekly (2017) Ozempic
T2DM indication: semaglutide 3/7/14 mg PO daily (2019) Rybelsus
Tirzepatide 5/10/15 mg SC weekly* Zepbound
T2DM indication: tirzepatide 5/10/15 mg SC weekly (2022) Mounjaro
Trade Name
Outline
Fun Facts (and non-fact phenomena)
Definitions
History of AOMs
Current Pharmacopeia
Mechanism/Dosing
Effectiveness
Side Effects/Adverse Events
Usage
Implications for Anesthesia and Surgery
Total Body Weight Loss %
1. Khera R, Murad MH, Chandar AK, Dulai PS, Wang Z, Prokop LJ, Loomba R, Camilleri M, Singh S. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA. 2016 Jun 14;315(22):2424-34.
2. Rubino DM, Greenway FL, Khalid U, O'Neil PM, Rosenstock J, Sørrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8
Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150.
3. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar
18;384(11):989-1002.
4. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216.
5. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014 Jan 1;311(1):74-86. doi: 10.1001/jama.2013.281361. PMID: 24231879; PMCID: PMC3928674.
-35%
-30%
-25%
-20%
-15%
-10%
-5%
0%
- ~3.5 kg
- 3.3%
- 5.4%
- 10%
- 6.4%
- 14.9%
- 15.0%
- 19.6%
- 20.9%
- 29.5%
- 31.9%
Total Body Weight Loss %
1. Khera R, Murad MH, Chandar AK, Dulai PS, Wang Z, Prokop LJ, Loomba R, Camilleri M, Singh S. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA. 2016 Jun 14;315(22):2424-34.
2. Rubino DM, Greenway FL, Khalid U, O'Neil PM, Rosenstock J, Sørrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8
Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150.
3. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar
18;384(11):989-1002.
4. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216.
5. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014 Jan 1;311(1):74-86. doi: 10.1001/jama.2013.281361. PMID: 24231879; PMCID: PMC3928674.
-35%
-30%
-25%
-20%
-15%
-10%
-5%
0%
- ~3.5 kg
- 3.3%
- 5.4%
- 10%
- 6.4%
- 14.9%
- 15.0%
- 19.6%
- 20.9%
- 29.5%
- 31.9%
Total Body Weight Loss %
1. Khera R, Murad MH, Chandar AK, Dulai PS, Wang Z, Prokop LJ, Loomba R, Camilleri M, Singh S. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA. 2016 Jun 14;315(22):2424-34.
2. Rubino DM, Greenway FL, Khalid U, O'Neil PM, Rosenstock J, Sørrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8
Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150.
3. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar
18;384(11):989-1002.
4. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216.
5. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014 Jan 1;311(1):74-86. doi: 10.1001/jama.2013.281361. PMID: 24231879; PMCID: PMC3928674.
-35%
-30%
-25%
-20%
-15%
-10%
-5%
0%
- ~3.5 kg
- 3.3%
- 5.4%
- 10%
- 6.4%
- 14.9%
- 15.0%
- 19.6%
- 20.9%
- 31.9%
Total Body Weight Loss %
1. Khera R, Murad MH, Chandar AK, Dulai PS, Wang Z, Prokop LJ, Loomba R, Camilleri M, Singh S. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA. 2016 Jun 14;315(22):2424-34.
2. Rubino DM, Greenway FL, Khalid U, O'Neil PM, Rosenstock J, Sørrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8
Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150.
3. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar
18;384(11):989-1002.
4. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216.
5. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014 Jan 1;311(1):74-86. doi: 10.1001/jama.2013.281361. PMID: 24231879; PMCID: PMC3928674.
-35%
-30%
-25%
-20%
-15%
-10%
-5%
0%
- ~3.5 kg
- 3.3%
- 10%
- 6.4%
- 14.9%
- 15.0%
- 19.6%
- 20.9%
- 31.9%
Total Body Weight Loss %
1. Khera R, Murad MH, Chandar AK, Dulai PS, Wang Z, Prokop LJ, Loomba R, Camilleri M, Singh S. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA. 2016 Jun 14;315(22):2424-34.
2. Rubino DM, Greenway FL, Khalid U, O'Neil PM, Rosenstock J, Sørrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8
Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150.
3. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar
18;384(11):989-1002.
4. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216.
5. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014 Jan 1;311(1):74-86. doi: 10.1001/jama.2013.281361. PMID: 24231879; PMCID: PMC3928674.
-35%
-30%
-25%
-20%
-15%
-10%
-5%
0%
- ~3.5 kg
- 3.3%
- 5.4%
- 10%
- 6.4%
- 14.9%
- 15.0%
- 19.6%
- 20.9%
- 31.9%
Total Body Weight Loss %
1. Khera R, Murad MH, Chandar AK, Dulai PS, Wang Z, Prokop LJ, Loomba R, Camilleri M, Singh S. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA. 2016 Jun 14;315(22):2424-34.
2. Rubino DM, Greenway FL, Khalid U, O'Neil PM, Rosenstock J, Sørrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8
Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150.
3. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar
18;384(11):989-1002.
4. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216.
5. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014 Jan 1;311(1):74-86. doi: 10.1001/jama.2013.281361. PMID: 24231879; PMCID: PMC3928674.
-35%
-30%
-25%
-20%
-15%
-10%
-5%
0%
- ~3.5 kg
- 3.3%
- 5.4%
- 10%
- 6.4%
- 14.9%
- 15.0%
- 19.6%
- 29.5%
- 31.9%
Total Body Weight Loss %
1. Khera R, Murad MH, Chandar AK, Dulai PS, Wang Z, Prokop LJ, Loomba R, Camilleri M, Singh S. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA. 2016 Jun 14;315(22):2424-34.
2. Rubino DM, Greenway FL, Khalid U, O'Neil PM, Rosenstock J, Sørrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8
Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150.
3. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar
18;384(11):989-1002.
4. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216.
5. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014 Jan 1;311(1):74-86. doi: 10.1001/jama.2013.281361. PMID: 24231879; PMCID: PMC3928674.
-35%
-30%
-25%
-20%
-15%
-10%
-5%
0%
- ~3.5 kg
- 3.3%
- 5.4%
- 10%
- 6.4%
- 15.0%
- 19.6%
- 29.5%
- 31.9%
Total Body Weight Loss %
1. Khera R, Murad MH, Chandar AK, Dulai PS, Wang Z, Prokop LJ, Loomba R, Camilleri M, Singh S. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA. 2016 Jun 14;315(22):2424-34.
2. Rubino DM, Greenway FL, Khalid U, O'Neil PM, Rosenstock J, Sørrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8
Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150.
3. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar
18;384(11):989-1002.
4. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216.
5. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014 Jan 1;311(1):74-86. doi: 10.1001/jama.2013.281361. PMID: 24231879; PMCID: PMC3928674.
-35%
-30%
-25%
-20%
-15%
-10%
-5%
0%
- ~3.5 kg
- 3.3%
- 5.4%
- 10%
- 6.4%
- 14.9%
- 15.0%
- 19.6%
- 29.5%
- 31.9%
Total Body Weight Loss %
1. Khera R, Murad MH, Chandar AK, Dulai PS, Wang Z, Prokop LJ, Loomba R, Camilleri M, Singh S. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA. 2016 Jun 14;315(22):2424-34.
2. Rubino DM, Greenway FL, Khalid U, O'Neil PM, Rosenstock J, Sørrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8
Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150.
3. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar
18;384(11):989-1002.
4. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216.
5. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014 Jan 1;311(1):74-86. doi: 10.1001/jama.2013.281361. PMID: 24231879; PMCID: PMC3928674.
-35%
-30%
-25%
-20%
-15%
-10%
-5%
0%
- ~3.5 kg
- 3.3%
- 5.4%
- 10%
- 6.4%
- 14.9%
- 15.0%
- 29.5%
- 31.9%
Total Body Weight Loss %
1. Khera R, Murad MH, Chandar AK, Dulai PS, Wang Z, Prokop LJ, Loomba R, Camilleri M, Singh S. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA. 2016 Jun 14;315(22):2424-34.
2. Rubino DM, Greenway FL, Khalid U, O'Neil PM, Rosenstock J, Sørrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8
Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150.
3. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar
18;384(11):989-1002.
4. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216.
5. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014 Jan 1;311(1):74-86. doi: 10.1001/jama.2013.281361. PMID: 24231879; PMCID: PMC3928674.
-35%
-30%
-25%
-20%
-15%
-10%
-5%
0%
- ~3.5 kg
- 3.3%
- 5.4%
- 10%
- 6.4%
- 14.9%
- 15.0%
- 29.5%
- 31.9%
- 19.6%
Total Body Weight Loss %
1. Khera R, Murad MH, Chandar AK, Dulai PS, Wang Z, Prokop LJ, Loomba R, Camilleri M, Singh S. Association of Pharmacological Treatments for Obesity With Weight Loss and Adverse Events: A Systematic Review and Meta-analysis. JAMA. 2016 Jun 14;315(22):2424-34.
2. Rubino DM, Greenway FL, Khalid U, O'Neil PM, Rosenstock J, Sørrig R, Wadden TA, Wizert A, Garvey WT; STEP 8 Investigators. Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8
Randomized Clinical Trial. JAMA. 2022 Jan 11;327(2):138-150.
3. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar
18;384(11):989-1002.
4. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216.
5. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014 Jan 1;311(1):74-86. doi: 10.1001/jama.2013.281361. PMID: 24231879; PMCID: PMC3928674.
-35%
-30%
-25%
-20%
-15%
-10%
-5%
0%
- ~3.5 kg
- 3.3%
- 5.4%
- 10%
- 6.4%
- 14.9%
- 15.0%
- 19.6%
- 20.9%
- 29.5%
- 31.9%
Outline
Fun Facts (and non-fact phenomena)
Definitions
History of AOMs
Current Pharmacopeia
Mechanism/Dosing
Effectiveness
Side Effects/Adverse Events
Usage
Implications for Anesthesia and Surgery
Adverse Effects
Short term (< 12 weeks)
Benzphetamine
Diethylpropion
Phentermine
Phendimetrazine
Long term
Orlistat
Phentermine/topiramate
Naltrexone/bupropion
Liraglutide
Semaglutide
Tirzepatide
Insomnia, irritability, anxiety, tachycardia, tremor,
headache, diarrhea
Adverse Effects
Short term (< 12 weeks)
Benzphetamine
Diethylpropion
Phentermine
Phendimetrazine
Long term
Orlistat
Phentermine/topiramate
Naltrexone/bupropion
Liraglutide
Semaglutide
Tirzepatide
Insomnia, irritability, anxiety, tachycardia, tremor,
headache, diarrhea
Oily spotting (27%), Flatus/discharge(24%), Fecal urgency (22%)
Adverse Effects
Short term (< 12 weeks)
Benzphetamine
Diethylpropion
Phentermine
Phendimetrazine
Long term
Orlistat
Phentermine/topiramate
Naltrexone/bupropion
Liraglutide
Semaglutide
Tirzepatide
Insomnia, irritability, anxiety, tachycardia, tremor,
headache, diarrhea
Oily spotting (27%), Flatus/discharge(24%), Fecal urgency (22%)
Constipation (15%), paresthesias (14%), dry mouth (14%)
Adverse Effects
Short term (< 12 weeks)
Benzphetamine
Diethylpropion
Phentermine
Phendimetrazine
Long term
Orlistat
Phentermine/topiramate
Naltrexone/bupropion
Liraglutide
Semaglutide
Tirzepatide
Insomnia, irritability, anxiety, tachycardia, tremor,
headache, diarrhea
Oily spotting (27%), Flatus/discharge(24%), Fecal urgency (22%)
Constipation (15%), paresthesias (14%), dry mouth (14%)
Diarrhea (7%), anxiety (4%), fatigue (4%), tremor (4%)
Adverse Effects
Short term (< 12 weeks)
Benzphetamine
Diethylpropion
Phentermine
Phendimetrazine
Long term
Orlistat
Phentermine/topiramate
Naltrexone/bupropion
Liraglutide
Semaglutide
Tirzepatide
Insomnia, irritability, anxiety, tachycardia, tremor,
headache, diarrhea
Oily spotting (27%), Flatus/discharge(24%), Fecal urgency (22%)
Constipation (15%), paresthesias (14%), dry mouth (14%)
Diarrhea (7%), anxiety (4%), fatigue (4%), tremor (4%)
Nausea (42%), Vomiting (34%), Diarrhea (22%), Low BG (15%)
Adverse Effects
Short term (< 12 weeks)
Benzphetamine
Diethylpropion
Phentermine
Phendimetrazine
Long term
Orlistat
Phentermine/topiramate
Naltrexone/bupropion
Liraglutide
Semaglutide
Tirzepatide
Insomnia, irritability, anxiety, tachycardia, tremor,
headache, diarrhea
Oily spotting (27%), Flatus/discharge(24%), Fecal urgency (22%)
Constipation (15%), paresthesias (14%), dry mouth (14%)
Diarrhea (7%), anxiety (4%), fatigue (4%), tremor (4%)
Nausea (42%), Vomiting (34%), Diarrhea (22%), Low BG (15%)
Nausea (44%), Diarrhea (30%), Vomiting (24%), Low BG (6%)
Adverse Effects
Short term (< 12 weeks)
Benzphetamine
Diethylpropion
Phentermine
Phendimetrazine
Long term
Orlistat
Phentermine/topiramate
Naltrexone/bupropion
Liraglutide
Semaglutide
Tirzepatide
Insomnia, irritability, anxiety, tachycardia, tremor,
headache, diarrhea
Oily spotting (27%), Flatus/discharge(24%), Fecal urgency (22%)
Constipation (15%), paresthesias (14%), dry mouth (14%)
Diarrhea (7%), anxiety (4%), fatigue (4%), tremor (4%)
Nausea (42%), Vomiting (34%), Diarrhea (22%), Low BG (15%)
Nausea (44%), Diarrhea (30%), Vomiting (24%), Low BG (6%)
Nausea (31%), Diarrhea (23%), Vomiting (12%), Low BG (2%)
Outline
Fun Facts (and non-fact phenomena)
Definitions
History of AOMs
Current Pharmacopeia
Mechanism/Dosing
Effectiveness
Side Effects/Adverse Events
Usage
Implications for Anesthesia and Surgery
Historical Use Boom or Bust
1996: 8,500 per 100,000
2011: 2,500 per 100,000 (2.74 M total)
2012-2016: 283 per 100,000 (<1M total)
Phentermine historically dominant
(89% in 2011)
Patients trying to lose weight:
3% reported use of an AOM
Ineffective Weight Loss (IWL) or
Weight Regain (WR)
after Bariatric Surgery
Use after RYGB and LAGB can
produce additional 5% TBWL
1. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014 Jan 1;311(1):74-86.
2. Hampp C, Kang EM, Borders-Hemphill V. Use of prescription antiobesity drugs in the United States. Pharmacotherapy. 2013 Dec;33(12):1299-307.
3. Nor Hanipah Z, Nasr EC, Bucak E, Schauer PR, Aminian A, Brethauer SA, Cetin D. Efficacy of adjuvant weight loss medication after bariatric surgery. Surg Obes Relat Dis. 2018 Jan;14(1):93-98.
Historical Use Out of Pocket $$
Payment most often out of
pocket
Insurance coverage
inconsistent
1. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014 Jan 1;311(1):74-86.
2. Hampp C, Kang EM, Borders-Hemphill V. Use of prescription antiobesity drugs in the United States. Pharmacotherapy. 2013 Dec;33(12):1299-307.
3. Nor Hanipah Z, Nasr EC, Bucak E, Schauer PR, Aminian A, Brethauer SA, Cetin D. Efficacy of adjuvant weight loss medication after bariatric surgery. Surg Obes Relat Dis. 2018 Jan;14(1):93-98.
Future Projections (as of 2023)
> 70 Million Americans with Obesity
Previous peak AOM use: 1996
Fen-Phen Fad, 8,500 rx/100,000 people
8,500 per 100,000 x 71M Obese = >6M prescriptions
1. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014 Jan 1;311(1):74-86.
2. Hampp C, Kang EM, Borders-Hemphill V. Use of prescription antiobesity drugs in the United States. Pharmacotherapy. 2013 Dec;33(12):1299-307.
3. Nor Hanipah Z, Nasr EC, Bucak E, Schauer PR, Aminian A, Brethauer SA, Cetin D. Efficacy of adjuvant weight loss medication after bariatric surgery. Surg Obes Relat Dis. 2018 Jan;14(1):93-98.
Future Projections (as of 2024)
93 Million Americans meet criteria for a GLP-1
74 Million Americans BMI > 30
Market Forecast: 20M Prescriptions/yr by 2030
This is not investment advice
PBM Forecast: Absolutely not
1% usage will increase total insurance spend by 5%
List Prices
Short term weekly yearly
Benzphetamine
Diethylpropion
Phentermine
Phendimetrazine
Long term
Orlistat (OTC)
Phentermine/topiramate
Naltrexone/bupropion
Liraglutide
Semaglutide
(Tirzepatide)
$30 $1,560
$27 $1,404
$25 $1,300
$23 $1,170
List Prices
Short term weekly yearly
Benzphetamine
Diethylpropion
Phentermine
Phendimetrazine
Long term
Orlistat (OTC)
Phentermine/topiramate
Naltrexone/bupropion
Liraglutide
Semaglutide
(Tirzepatide)
$30 $1,560
$27 $1,404
$25 $1,300
$23 $1,170
$54 $2,808
List Prices
Short term weekly yearly
Benzphetamine
Diethylpropion
Phentermine
Phendimetrazine
Long term
Orlistat (OTC)
Phentermine/topiramate
Naltrexone/bupropion
Liraglutide
Semaglutide
(Tirzepatide)
$30 $1,560
$27 $1,404
$25 $1,300
$23 $1,170
$54 $2,808
$50 $2,600
List Prices
Short term weekly yearly
Benzphetamine
Diethylpropion
Phentermine
Phendimetrazine
Long term
Orlistat (OTC)
Phentermine/topiramate
Naltrexone/bupropion
Liraglutide
Semaglutide
(Tirzepatide)
$30 $1,560
$27 $1,404
$25 $1,300
$23 $1,170
$54 $2,808
$50 $2,600
$165 $8,580
List Prices
Short term weekly yearly
Benzphetamine
Diethylpropion
Phentermine
Phendimetrazine
Long term
Orlistat (OTC)
Phentermine/topiramate
Naltrexone/bupropion
Liraglutide
Semaglutide
(Tirzepatide)
$30 $1,560
$27 $1,404
$25 $1,300
$23 $1,170
$54 $2,808
$50 $2,600
$165 $8,580
$315 $16,368
List Prices
Short term weekly yearly
Benzphetamine
Diethylpropion
Phentermine
Phendimetrazine
Long term
Orlistat (OTC)
Phentermine/topiramate
Naltrexone/bupropion
Liraglutide
Semaglutide
(Tirzepatide)
$30 $1,560
$27 $1,404
$25 $1,300
$23 $1,170
$54 $2,808
$50 $2,600
$165 $8,580
$315 $16,368
$1,349 $70,148
List Prices
Short term weekly yearly
Benzphetamine
Diethylpropion
Phentermine
Phendimetrazine
Long term
Orlistat (OTC)
Phentermine/topiramate
Naltrexone/bupropion
Liraglutide
Semaglutide
Tirzepatide
$30 $1,560
$27 $1,404
$25 $1,300
$23 $1,170
$54 $2,808
$50 $2,600
$165 $8,580
$315 $16,368
$1,349 $70,148
$1,023 $53,198
List Prices
Short term weekly yearly
Benzphetamine
Diethylpropion
Phentermine
Phendimetrazine
Long term
Orlistat (OTC)
Phentermine/topiramate
Naltrexone/bupropion
Liraglutide
Semaglutide
Tirzepatide
$30 $1,560
$27 $1,404
$25 $1,300
$23 $1,170
$54 $2,808
$50 $2,600
$165 $8,580
$315 $16,368
$1,349 $70,148
$1,023 $53,198
Future Projections
6M prescriptions * $50,000 = $300 Billion
20M prescriptions * $50,000 = $1 Trillion
CMS Annual Budget = ~$1 Trillion
1. Yanovski SZ, Yanovski JA. Long-term drug treatment for obesity: a systematic and clinical review. JAMA. 2014 Jan 1;311(1):74-86.
2. Hampp C, Kang EM, Borders-Hemphill V. Use of prescription antiobesity drugs in the United States. Pharmacotherapy. 2013 Dec;33(12):1299-307.
3. Nor Hanipah Z, Nasr EC, Bucak E, Schauer PR, Aminian A, Brethauer SA, Cetin D. Efficacy of adjuvant weight loss medication after bariatric surgery. Surg Obes Relat Dis. 2018 Jan;14(1):93-98.
Outline
Fun Facts (and non-fact phenomena)
Definitions
History of AOMs
Current Pharmacopeia
Mechanism/Dosing
Effectiveness
Side Effects/Adverse Events
Usage
Implications for Anesthesia and Surgery
GLP-1 RA Implications
for Bariatric Surgery
Most effective weight loss medications to date
Side effects better-tolerated or less severe than earlier medications
More patients will be asking and using these before and after surgery
Insurance coverage will continue to vary
GLP-1 RA Implications
for Bariatric Surgery
Durability of effects dependent on
continued use
Effectiveness does not surpass that of
bariatric surgery
Opportunity for on-ramp to
comprehensive weight management
programs
Some effects of bariatric surgery are
GLP-1 independent
Drucker DJ. Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1.
Cell Metab. 2018 Apr 3;27(4):740-756.
GLP-1 RA Implications
for Bariatric Surgery
May eventually increase bariatric surgery utilization
Important adjunct (adjuvant therapy) for bariatric surgery
TBWL of 6-9% with GLP-1 RAs
5 years after bariatric surgery
Weight regain
Ineffective weight loss
Relationship between GLP-1 RAs and bariatric surgery needs further study
1. Lautenbach A, Wernecke M, Huber TB, Stoll F, Wagner J, Meyhöfer SM, Meyhöfer S, Aberle J. The Potential of Semaglutide Once-Weekly in Patients Without Type 2 Diabetes with Weight Regain or
Insufficient Weight Loss After Bariatric Surgery-a Retrospective Analysis. Obes Surg. 2022 Oct;32(10):3280-3288.
2. Jensen AB, Renström F, Aczél S, Folie P, Biraima-Steinemann M, Beuschlein F, Bilz S. Efficacy of the Glucagon-Like Peptide-1 Receptor Agonists Liraglutide and Semaglutide for the Treatment of
Weight Regain After Bariatric surgery: a Retrospective Observational Study. Obes Surg. 2023 Apr;33(4):1017-1025. doi: 10.1007/s11695-023-06484-8. Epub 2023 Feb 11. PMID: 36765019; PMCID:
PMC9918402.
Conclusions
Historical use of AOMs has been low
Limited by significant side effects, small effect size, temporary results
Out-of-pocket payment has been the norm
Recent GLP-1 RAs are the most effective AOMs to date
Opportunity to strengthen comprehensive weight management
Risk of another fad or boom/bust cycle
Patients will want to know our recommendations
Questions