Obesity remains a pervasive health challenge affecting a significant portion of the population worldwide, with implications extending beyond physical appearance to encompass profound metabolic and cardiovascular risks. As medical understanding evolves, the focus on effective weight management strategies has intensified, supported by advancements in pharmacotherapy.
As recommendations and anti-obesity medications (AOM) pharmacotherapies evolve, understanding the guidelines from leading medical societies such as the Obesity Medicine Association (OMA), American Gastroenterological Association (AGA), and American Association of Clinical Endocrinology (AACE) becomes increasingly crucial.
This article compares and analyzes their recommendations for various pharmacotherapies designed to combat obesity, with the aim being to equip healthcare providers with the insights necessary to optimize patient care through evidence-based, personalized treatment strategies.
Titles of Comparison:
1 - Obesity Algorithm 2024 Update: Pharmacological Management of Obesity
- Society: Obesity Medicine Association
- Publication Date: February 2024
- Objective: Provides recommendations for the pharmacological management of obesity.
- Target Population: Individuals with obesity or indication for weight management therapies over 12 years of age.
- Methodology: Ungraded key takeaway recommendations
- Graded Strength of Recommendations: No
- Graded Level of Evidence: No
- Systematic Review Conducted: Not stated
- Literature Review Conducted: Yes
- Internal Review Conducted: Yes
- External Review Conducted: Unknown
- COIs & Funding Source Disclosed: Yes
- Full Text | Overview
2 - AGA 2022 Clinical Practice Guideline on Pharmacological Interventions for Adults with Obesity
- Society: American Gastroenterological Association
- Publication Date: November 2022
- Objective:
- This guideline provides evidence-based recommendations for the pharmacological management of obesity in adults. Although the management of obesity in children is of critical importance, it is beyond the scope of this guideline to address the pharmacological treatment of childhood obesity.
- Target Population:
- Adults with overweight and obesity (body mass index ≥30 kg/m2, or ≥27 kg/m2 with weight-related complications) who have an inadequate response to lifestyle interventions.
- Methodology: GRADE framework
- Graded Strength of Recommendations: Yes
- Graded Level of Evidence: Yes
- Systematic Review Conducted: Yes
- Literature Review Conducted: Yes
- Internal Review Conducted: Yes
- External Review Conducted: Yes
- COIs & Funding Source Disclosed:
- Full Text | Guideline Summary
Table 1. Obesity Pharmacotherapy Recommendations by Society
| Anti-Obesity Pharmacotherapies | Obesity Algorithm 2024 Update: Pharmacological Management of Obesity (OMA) | 2022 Clinical Practice Guideline on Pharmacological interventions for Adults with Obesity (AGA) |
|---|---|---|
| GLP-1 agonists | ||
| liraglutide | Dose: 3mg subQ qd for treatment of obesity (ages >12 years) 1.8mg qd for treatment of T2DM Average weight loss: 7-8% of body weight Monitor for low blood sugar when patients on concomitant anti-diabetes medications, particularly insulins or sulfonylureas | Dose: 3mg subQ QD Average total body weight loss: 4.8% |
| semaglutide | Dose: Weekly subQ injections, indicated for treatment of obesity (ages >12 years) Average weight loss: 15-16% of body weight Monitor for low blood sugar when patients on concomitant anti-diabetes medications, particularly insulins or sulfonylureas Can worsen pre-existing diabetic retinopathy | Dose: 2.4mg subQ once weekly Average total body weight loss: 10.8% |
| GLP-1/GIP dual agonists | ||
| tirzepatide | Dose: Weekly subQ injections Average weight loss: 20% of body weight Monitor for low blood sugar when patients on concomitant anti-diabetes medications, particularly insulins or sulfonylureas | At the time of CPG’s publication, tirzepatide had been approved for the T2DM indication by the FDA, but results from a phase 3 clinical trial in participants without T2DM, at the highest dose of tirzepatide 15 mg weekly, demonstrated mean weight loss of 21% after 72 weeks of treatment. Nearly 40% of subjects on treatment at the maximum dose demonstrated ≥25% TBWL. |
| Sympathomimetics | ||
| phentermine/topiramate ER | Dose: 3.75mg/23mg PO qAM (max 7.5mg/46mg) Average weight loss: 10% of body weight Monitor for low blood sugar when patients on concomitant anti-diabetes medications | Dose: 7.5mg/46mg PO qAM;15mg/92mg qAM Average total body weight loss: 8.5% |
| phentermine | Dose: 1-3 tablets or capsules PO, taken QD up to TID Reported weight loss varies: 5-12% after 3-6 months FDA approved for short-term 12 week course, but data supports use longer than 12 weeks A reduction in insulin or oral hypoglycemic medications may be necessary to prevent hypoglycemia Contraindicated in patients taking or haven taken within the last 14 days MAO-inhibitors due to risk of hypertensive crisis | Dose: 4-8mg PO TID; 15-37.5mg PO qAM Average weight loss: 3.6% of body weight Avoid in patients with uncontrolled hypertension or history of cardiovascular disease; BP & HR should be monitored periodically while taking Avoid in patients who are pregnant given potential teratogenic effects of in utero topiramate exposure Can benefit patients with comorbid migraines |
| diethylpropion | Not explicitly discussed | Dose: 25mg PO TID qAc (one hour before meals); Sustained-release 75mg tab PO QD mid-morning Average total body weight loss: 5.4% FDA approved for short-term 12 week course, but data supports off-label use for longer than 12 weeks Avoid in patients with uncontrolled hypertension or history of cardiovascular disease; BP & HR should be monitored periodically while taking |
| Opioid Antagonist/SDRIs | ||
| naltrexone/bupropion | Dose: BID tablets (not at meals) of 8mg/90mg increased weekly x 4 Average weight loss: 5-6% of body weight Bupropion is a CYP2D6 inhibitor, and can increase drug concentrations of other medicines metabolized by CYP2D6 Bupropion can lower seizure threshold and should be used with caution in patients with increased risk of seizures Black box warning: Increased risk of suicidal thoughts and behaviors in people younger than 24 years of age who have depression | Dose: naltrexone/bupropion ER - 32mg/180mg PO BID Bupropion can lower seizure threshold and should be used with caution in patients with increased risk of seizures Contraindicated in patients on MAO-inhibitors, opioid therapy, or severe renal/hepatic disease |
| Superabsorbent Hydrogel | ||
| Gelesis 100 | Not discussed | Dose: 3 capsules with water PO qAc Average total body weight loss: 2% Indicated for adults with BMI 25-40 kg/m2 only in the context of a clinical trial, recommend neither for nor against the use of Gelesis 100 |
| Lipase Inhibitors | ||
| orlistat | Dose: 60-120mg PO TID Average weight loss: 5% of body weight | Recommend against the use of orlistat Patients who place high value on small potential weight loss benefit and low value on adverse GI effects may reasonably choose this treatment, but note that the average total body weight loss is about 2% |
| Melanocortin-4 receptor agonist | ||
| setmelanotide | Dose: 1-3mg subQ qd Indicated for patients >6 years of age with genetic obesity due to a POMC, PCSK1, or LEPR deficiency and for Bardet-Biedel syndrome | Not discussed – was approved by the FDA in 2020 for the treatment of rare genetic causes of obesity but was not included in these guidelines as it was outside the scope of the review |
| Leptin analogs | ||
| metreleptin | Dose (starting dose): Men – 2.5mg subQ QD Women – 5mg subQ QD (max 10mg) For patients with congenital or acquired generalized lipodystrophy | Not discussed |
Key Takeaways for Obesity Pharmacotherapies
- Anti-obesity medications are a tool for treatment of overweight/obese patients but are not intended as a cure and should always be used in conjunction with lifestyle modifications.
- Weight loss response to anti-obesity drugs is variable depending on the agent, dosing, and individual characteristics of each patient, but there is potential for weight gain if/when medications are discontinued.
- A 3–7% weight loss from baseline in overweight/obese patients improves glycemic control and other cardiovascular risk factors, with sustained loss of >10% of body weight usually confers greater benefits, including possible remission of type 2 diabetes.
GLP-1 agonists (semaglutide, liraglutide) & Dual GLP-1/GIP agonists (tirzepatide)
- Uniformly across both societies, the use of GLP-1 agonists or dual GLP-1/GIP agonists is the preferred pharmacotherapy recommended for the best efficacy in supporting weight management and glycemic control to help mitigate potential cardiometabolic sequalae of T2DM.
- Tirzepatide showed the most benefit for weight loss, with patients typically losing 15-20% of their baseline body weight, with semaglutide close behind with an average of 10-15% weight loss.
- Liraglutide showed similar benefit, though less in magnitude than semaglutide, for weight management with an average weight loss of 5-10%.
- Semaglutide should be used with caution in patients with comorbid diabetic retinopathy.
Sympathomimetics
- Most medications from this drug class showed a 5-10% reduction in body weight.
- Medications like diethylpropion and phentermine have been FDA-approved for short term (<3 month) weight management use.
- Opinion experts and emerging data support the use of off-label longer durations of therapy for appropriate patients.
- All sympathomimetics carry the risk of increased blood pressure and heart rate and should be routinely monitored in patients prescribed these medications.
- Uncontrolled hypertension and history of cardiovascular disease are relative contraindications for these drugs.
- Combination phentermine/topiramate ER and phentermine monotherapy were recommended by both the OMA and AGA for weight control.
Miscellaneous & Comorbidity-Related Pharmacotherapies
- Naltrexone/Bupropion were recommended by both societies for weight management in overweight/obese patients
- Use caution for patients with epilepsy or increased risk of seizures given bupropion risk of lowering seizure threshold. Naltrexone-including regimens/therapies should not be used for patients receiving MAT or using opioid-containing therapies
- Orlistat was recommended by the OMA for weight management.
- Orlistat, however, was not recommended by the AGA given its low relative weight-loss efficacy and higher risk of GI-related side effects.
- Metreleptin and setmelanotide both have benefits for weight management related to genetic etiologies of obesity, but do not have specific indications or recommendations regarding the benefit or indication for overweight/obese patients without certain underlying genetic disorders.
- Gelesis 100 was given a recommendation neither for nor against the use of this pharmacotherapy by the AGA.
Medications originally indicated for diabetes like semaglutide and tirzepatide are now receiving FDA approval for weight management indications, and promising newcomers like retatrutide have garnered widespread attention and investment in obesity care. The synergy between lifestyle changes and AOM for overweight or obese patients underscores the importance of these therapies in reducing the risk of potential comorbidities and cardiometabolic sequalae that can come about without a weight management treatment plan.
With that, we wrap up this Guideline Side-By-Side comparison of the recommendations for obesity & weight management pharmacotherapies in the management of overweight and obese adult patients. When comparing side-by-side, recommendations can be synthesized to build treatment plans individualized for the weight management care that each patient deserves.
This concludes our Guidelines Side-by-Side on Anti-Obesity Medications. Sign up for alerts and stay informed on the latest published guidelines and articles.
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