MAXIMIZING OUTCOMES: THE IMPACT OF ORAL MEDICATIONS ON WEIGHT MANAGEMENT
Faculty:
L. Austin Fredrickson, MD, FACP
L. Austin Fredrickson, MD, FACP, is an Associate Professor of Internal Medicine at Northeast Ohio Medical University, where he serves as core faculty and teaches diagnostics, therapeutics, clinical skills, and health humanities. He is board-certified in general internal medicine and practices rural primary care. 
Susan Bowlin, DNP, FNP-BC, ACNP-BC, CBN
Dr. Susan Bowlin, DNP, FNP-BC, ACNP-BC, CBN, is a double-board-certified nurse practitioner with over 25 years of experience in family practice, acute care, and obesity medicine. She is the founder of Priority One Weight Loss, where she specializes in evidence-based obesity care, empowering patients to achieve sustainable health and vitality. Dr. Bowlin holds a Certificate of Advanced Education in Obesity Medicine. She is a national speaker and educator on cardiometabolic disease and a founding member and treasurer of the Dallas Obesity Society. An active leader in her field, Dr. Bowlin is dedicated to transforming lives through compassionate care, patient-centered solutions, and innovative treatment modalities.
Liz Fredrickson, PharmD, BCPS
Liz Fredrickson is an Associate Professor of Pharmacy Practice and Pharmaceutical Sciences at the Northeast Ohio Medical University (NEOMED) College of Pharmacy.
Pamela Sardo, PharmD, BS
Pamela Sardo is a freelance medical writer, pharmacist licensed in 2 states, and the founder/principal at Sardo Solutions. She received her BS from the University of Connecticut and a PharmD from the University of Rhode Island. Pam’s career spans many years in retail, clinics, hospitals, long-term care, Veterans Affairs, pharmaceutical manufacturing, and managed healthcare across broad therapeutic classes and disease states.
Abstract
Oral anti-obesity medications (AOMs) serve as valuable tools in the management of obesity. Current guidelines advocate for a multimodal approach to obesity treatment, incorporating lifestyle interventions such as diet and exercise alongside pharmacotherapy when appropriate. The decision to initiate an oral AOM should be tailored to the patient’s weight-loss goals, comorbidities, and the medication’s safety profile. This educational activity provides an in-depth review of the mechanisms of action, dosing strategies, and the efficacy and safety profiles of oral AOMs. Additionally, this activity emphasizes the critical role of long-term monitoring, shared decision-making, and interprofessional collaboration in ensuring these therapies are used safely and effectively to optimize patient outcomes.
Accreditation Statements
In support of improving patient care, RxCe.com LLC is jointly accredited by the Accreditation CouncilTM for Continuing Medical Education (ACCME®), the Accreditation Council for Pharmacy Education (ACPE®), and the American Nurses Credentialing Center (ANCC®), to provide continuing education for the healthcare team.
This activity was planned by and for the healthcare team, and learners will receive 2 Interprofessional Continuing Education (IPCE) credits for learning and change.
Joint Universal Activity Number: The Joint Accreditation Universal Activity Numbers assigned to this activity are as follows:
Pharmacists: JA4008424-0000-26-040-H01-P
Pharmacy Technicians: JA4008424-0000-26-040-H01-T
Credits: 2 contact hour(s) (0.2 CEU(s)) of continuing education credit.
Credit Types:
IPCE Credits - 2 Credits
AAPA Category 1 Credit™️ - 2 Credits
AMA PRA Category 1 Credit™️ - 2 Credits
Pharmacy - 2 Credits
Type of Activity: Knowledge
Media: Computer-Based Training (i.e., online courses)
Estimated time to complete activity: 2 contact hour(s) (0.2 CEU(s)), including Activity Pre-Test, Post-Test, and Activity Evaluation.
Release Date: March 30, 2026 Expiration Date: March 30, 2029
Target Audience: This educational activity is for Physicians, Physician Assistants, Pharmacists, and Pharmacy Technicians
How to Earn Credit: From March 30, 2026, through March 30, 2029, participants must:
Read the “learning objectives” and “author and planning team disclosures;”
Take the “Educational Activity Pre-Test;”
Study the section entitled “Educational Activity;” and
Complete the Educational Activity Post-Test and Activity Evaluation. The Educational Activity Post-Test will be graded automatically. Following successful completion of the Educational Activity Post-Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)
CME Credit: Credit for this course will be uploaded to CPE Monitor® for pharmacists. Physicians may receive AMA PRA Category 1 Credit™️ and use these credits toward Maintenance of Certification (MOC) requirements. Physician Assistants may earn AAPA Category 1 CME credit, reportable through PA Portfolio. All learners shall verify their individual licensing board’s specific requirements and eligibility criteria.
Statement of Need
Obesity is a chronic and complex disease that requires a long-term, multifaceted approach to treatment. An understanding of oral anti-obesity medications (AOMs) is essential for the management of obesity. Current guidelines advocate for a multimodal approach to obesity treatment, incorporating lifestyle interventions such as diet and exercise alongside pharmacotherapy when appropriate. This educational activity aims to address this gap by providing an in-depth review of the mechanisms of action, dosing strategies, and the efficacy and safety profiles of oral AOMs. Additionally, this activity emphasizes the critical role of long-term monitoring, shared decision-making, and interprofessional collaboration in ensuring these therapies are used safely and effectively to optimize patient outcomes.
Learning Objectives: Upon completion of this educational activity, participants should be able to:
Compare and Contrast the mechanisms of oral anti-obesity medications (AOMs) in weight management
Describe the efficacy and safety of oral AOMs
Identify interprofessional collaboration strategies to optimize treatment outcomes
Educate patients on the appropriate use of oral AOMs
Disclosures
The following individuals were involved in planning, developing, and/or authoring this activity: L. Austin Fredrickson, MD, FACP; Liz Fredrickson, PharmD, BCPS; Susan Bowlin, DNP, FNP-BC, ACNP-BC, CBN; and Pamela Sardo, PharmD, BS. None of the individuals involved in developing this activity has a conflict of interest or financial relationships related to the subject matter. Susan Bowlin is a member of the Speaker’s Bureau for Eli Lilly and Novo Nordisk. Any potential conflicts of interest were mitigated. There are no financial relationships or commercial or financial support relevant to this activity to report or disclose by RxCe.com or any of the individuals involved in the development of this activity.
© RxCe.com LLC 2026: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.
Educational Activity Pre-Test
Which of the following oral AOMs works by inhibiting dietary fat absorption?
Phentermine
Orlistat
Naltrexone-bupropion
Phentermine-topiramate
Which AOM should be avoided in patients with uncontrolled hypertension due to its potential to increase heart rate and blood pressure?
Orlistat
Phentermine
Naltrexone-bupropion
Phentermine-topiramate
Which oral AOM is contraindicated in pregnancy due to teratogenic risks?
Phentermine-topiramate
Naltrexone-bupropion
Orlistat
Phentermine
Educational Activity
Maximizing Outcomes: The Impact of Oral Medications on Weight Management
Introduction
Oral anti-obesity medications (AOMs) serve as valuable tools in the management of obesity. Current guidelines advocate for a multimodal approach to obesity treatment, incorporating lifestyle interventions such as diet and exercise alongside pharmacotherapy when appropriate.1,2 The decision to initiate an oral AOM should be personalized, considering the patient’s weight loss goals, comorbidities, and the medication’s safety profile.1 Table 1 provides an overview of the American Association of Clinical Endocrinologists (AACE)/American College of Endocrinology (ACE) approach to diagnosing and managing obesity.1
Table 1
Diagnosis and Medical Management of Obesity1
| Anthropometric Component- Body Mass Index (BMI) kg/m² | Clinical Component | Disease Stage | Chronic Disease Phase of Prevention | Suggested Therapy (based on clinical judgment) |
|---|---|---|---|---|
| BMI <25 | <23 in certain ethnicities, waist circumference below regional/ ethnic cutoffs | Normal weight (no obesity) | Primary | Healthy lifestyle: healthy meal plan/physical activity |
| BMI 25-29.9 | 23-24.9 in certain ethnicities | Overweight stage 0 (no complications) | Secondary | Lifestyle therapy: Reduced-calorie healthy meal plan/physical activity/ behavioral interventions |
| BMI ≥30 | ≥25 in certain ethnicities | Obesity stage 0- no complications | Secondary | Lifestyle therapy: Reduced-calorie healthy meal plan/physical activity/ behavioral interventions |
| BMI ≥25 | ≥23 in certain ethnicities | Obesity stage 1 (1 or more mild to moderate complications) | Tertiary | Lifestyle therapy: Reduced-calorie healthy meal plan/physical activity/ behavioral interventions |
| BMI ≥25 | ≥23 in certain ethnicities | Obesity stage 2 (at least 1 severe complication) | Tertiary | Lifestyle therapy: Reduced-calorie healthy meal plan/physical activity/ behavioral interventions |
This educational activity will provide an in-depth review of the mechanisms of action, dosing strategies, and the efficacy and safety profiles of oral AOMs. Additionally, this activity will emphasize the critical role of long-term monitoring, shared decision-making, and interprofessional collaboration in ensuring these therapies are used safely and effectively to optimize patient outcomes.
Mechanisms and Effectiveness of Oral AOMs
Oral AOMs vary in their mechanisms of action, effectiveness, and suitability for different patient populations. They can be categorized as either intra-gastrointestinal agents or centrally acting agents.3 Intra-gastrointestinal agents act locally within the gastrointestinal (GI) tract to reduce calorie absorption. This localized action limits systemic effects, with side effects typically confined to the GI tract, including oily stools, flatulence, and fecal urgency.3,4,5 In contrast, centrally acting agents target the central nervous system (CNS) to suppress appetite, enhance satiety, or regulate energy expenditure by influencing hypothalamic and mesolimbic pathways.3,4 These agents have systemic effects due to CNS involvement and are associated with side effects such as mood changes, nausea, and increased heart rate.3,4
Orlistat
Orlistat is the only FDA-approved intra-gastrointestinal AOM.5 It acts as a reversible inhibitor of pancreatic and gastric lipases and can inhibit dietary fat absorption by 30%.5 It is recommended to be used as an adjunct to diet and exercise for weight management in patients with a BMI ≥30 kg/m² or those with a BMI ≥27 kg/m² and at least one weight-associated comorbidity (e.g., hypertension, dyslipidemia).1,2,5 The recommended dose of Xenical® is 120 mg orally three times daily with each main meal that contains fat, taken during or within one hour of the meal.6 Doses should be skipped if a meal is missed or contains no fat.6 Some experts recommend starting with a lower dose of 60 mg (available as Alli©) to improve GI tolerability or switching to the 60 mg dose if the 120 mg dose is poorly tolerated.6,7 Alli® (available over-the-counter (OTC)), is dosed at 60 mg orally three times daily with fat-containing meals and has a maximum dose of 180 mg/day.6 Discontinuation of orlistat should be considered if weight loss is less than 4% to 5% of baseline body weight after three months of use.5
While its efficacy is modest—providing an average weight loss of 3.1% compared with placebo—it offers patients additional cardiometabolic benefits, including reductions in LDL cholesterol, systolic blood pressure, and the risk of developing type 2 diabetes. However, it is associated with notable GI side effects, including oily fecal spotting (27%), steatorrhea (20%), and fecal urgency (22%), which often lead to decreases in long-term adherence. Patients can be counseled that these side effects often diminish within 4 weeks of starting the medication and can be mitigated by following a low-fat diet.3-7 Patients using orlistat should also be counseled to take a multivitamin at bedtime to offset the potential for reduced absorption of fat-soluble vitamins.3
Orlistat is also considered effective for obesity-related complications such as nonalcoholic fatty liver disease, where it may aid in reducing hepatic steatosis and inflammation when paired with a calorie-restricted diet and physical activity.1 It may also be used in patients with polycystic ovary syndrome (PCOS) to improve hyperandrogenism and metabolic parameters.1 However, its use is contraindicated in patients with oxalate nephropathy or a history of nephrolithiasis due to increased risk.1 For patients with cardiovascular risk factors, orlistat is considered a safe option due to its neutral effect on heart rate and blood pressure.1
In clinical practice, orlistat's use should be individualized based on patient-specific factors, and adherence should be monitored closely to maximize benefits. Notably, the AGA guidelines recommend against using orlistat; however, they note that it may be useful for patients who value modest weight-loss benefits and are willing to tolerate the associated GI side effects, despite its limited effectiveness. Orlistat remains a viable option for patients seeking cardiometabolic benefits but who may not tolerate other AOMs.3
Phentermine
Phentermine is a centrally acting medication that suppresses appetite by affecting norepinephrine in the hypothalamus.8 It is indicated for short-term use (up to 12 weeks) as an adjunct to diet and exercise for weight management in patients with a BMI ≥30 kg/m² or those with a BMI ≥27 kg/m² and at least one weight-associated comorbidity, such as dyslipidemia.1,8 It should be avoided in patients with heart disease or poorly controlled hypertension.1 The dosing of phentermine is expressed in terms of the salt, phentermine hydrochloride. For capsules and tablets (excluding Lomaira®), the typical dose is 15 to 18.75 mg once daily or 30 to 37.5 mg daily, taken as a single dose or divided into two doses.8 For Lomaira tablets, the recommended dose is 8 mg three times daily, taken 30 minutes before meals.8
Patients who take phentermine may achieve moderate weight loss of 4% to 6%, and it is among the most affordable AOMs.3 However, its long-term use is off-label, and concerns remain about its cardiovascular safety profile.3 Common side effects include dry mouth, insomnia, and headache, which may improve with dose adjustments.8 The AACE/ACE guidelines recommend that phentermine be avoided in patients with uncontrolled hypertension or cardiovascular disease due to potential risks such as increased heart rate and blood pressure.1 The AGA guidelines suggest the use of phentermine with lifestyle modifications, but also recommend it be avoided in patients with a history of cardiovascular disease.2
Phentermine-Topiramate
Phentermine-topiramate extended-release is recommended for chronic weight management, in combination with diet and exercise, in patients with a BMI ≥30 kg/m² or with a BMI ≥27 kg/m² and at least one weight-associated comorbidity, such as dyslipidemia, type 2 diabetes, or hypertension.1,9 The combination enhances weight loss through dual mechanisms: phentermine suppresses appetite by releasing norepinephrine, while topiramate, an anticonvulsant, promotes satiety (feeling well-fed) by modulating GABAergic activity and suppressing food cravings.3,9 The initial dose is 3.75 mg/23 mg once daily for 14 days, followed by an increase to 7.5 mg/46 mg once daily for 12 weeks.9 After 12 weeks, if at least 3% of baseline body weight has not been lost, therapy should either be discontinued with a gradual taper (e.g., switching to every-other-day dosing for at least one week before stopping) or escalated to a higher dose based on tolerability and patient preference.9 If escalation is chosen, the dose can be increased to 11.25 mg/69 mg once daily for 14 days, and then to a maximum dose of 15 mg/92 mg once daily.9 After 12 weeks on the maximum dose, therapy should be discontinued with gradual tapering if at least 5% of baseline body weight has not been achieved.9
The combination of phentermine and topiramate produces synergistic effects, resulting in significant and sustained weight loss of 8% to 10%.3 It is particularly beneficial for patients with comorbid conditions such as controlled hypertension and diabetes, as it can improve blood pressure and glycemic control.3 However, it requires careful monitoring due to risks of teratogenicity and psychiatric side effects.3 Taking the combination of phentermine-topiramate ER within 14 days of taking a monoamine oxidase inhibitor is contraindicated in glaucoma patients due to an increased risk of a hypertensive crisis. It is also contraindicated in pregnancy due to teratogenic risks, necessitating reliable contraception in women of childbearing potential.1 Other potential side effects include mood changes, cognitive effects, and elevated heart rate.9
Naltrexone-Bupropion
Naltrexone-bupropion extended-release is a centrally acting medication approved for chronic weight management in patients with a BMI ≥30 kg/m² or ≥27 kg/m² with at least one weight-related comorbidity.10 The combination works by targeting the hypothalamus and the mesolimbic reward system. Bupropion enhances dopamine and norepinephrine activity to reduce appetite, while naltrexone blocks opioid receptors to suppress food cravings.
The medication is initiated at a low dose and titrated to a target dose of 32 mg daily or 360 mg administered as two tablets twice daily.10 Common side effects include nausea, headache, insomnia, and constipation. Naltrexone-bupropion is contraindicated in patients with angle closure glaucoma, current opioid therapy, uncontrolled hypertension, seizure disorders, or a history of eating disorders.10 It also carries a boxed warning for potential neuropsychiatric side effects, such as suicidal thoughts, and should be used with caution in patients with depression or other mood disorders.1
By targeting appetite and cravings via central mechanisms, naltrexone-bupropion achieves a modest weight loss of 4.1% compared with placebo.3 It is more effective when combined with intensive behavioral therapy.3 It has minimal impact on cardiovascular risk factors but requires careful monitoring for blood pressure elevations due to the bupropion component.3
Comparison of Anti-Obesity Drugs for Obesity Management
When selecting an oral AOM in clinical practice, clinicians should adopt an individualized, evidence-based approach guided by patient-specific factors, including BMI, weight-related comorbidities, prior treatment history, and potential contraindications.1,2 According to the AACE/ACE guidelines, the decision to initiate pharmacologic therapy should be based on the patient’s inability to achieve or sustain weight loss through lifestyle interventions alone, with consideration given to comorbidity burden and the need for long-term weight management.1
When considering options for prescribing AOMs to a patient, the AGA guidelines recommend that clinicians select AOMs based on their efficacy, safety profiles, and mechanisms of action, tailored to the patient’s needs.2 For example, phentermine/topiramate may be preferred for patients who require significant weight loss, while naltrexone/bupropion ER could be beneficial for individuals with binge-eating behaviors or concurrent smoking cessation needs.1,2
Additionally, medication tolerability, potential side effects, drug interactions, and insurance coverage should all be factored into the decision-making process. Shared decision-making is essential to enhance adherence, ensuring that patients are educated about expected outcomes, side effects, and the importance of combining pharmacologic therapy with sustained lifestyle modifications. Regular follow-up is necessary to monitor response and adjust treatment as needed, reinforcing the chronic nature of obesity management.
Table 2 summarizes the AACE/ACA Clinical Practice Guidelines for recommendations and monitoring related to prescribing oral AOMs.1 The table includes monitoring in cases where experts believe “insufficient data” is available or when use is “not recommended.” Weight loss medications may cause euphoria, which can contribute in part to the risk of misuse.11,12
Table 3 summarizes weight loss and cardiovascular changes.3 Clinicians should always refer to the prescribing information for each pharmaceutical agent for comprehensive safety and efficacy information.
Table 2
AACE/ACE Monitoring and Use Recommendations for Oral AOMs1
| Clinical Characteristics or Co-Existing Diseases | Orlistat | Phentermine/ topiramate ER | Naltrexone ER/ bupropion ER |
|---|---|---|---|
| Diabetes Prevention (metabolic syndrome, prediabetes) | Insufficient data | ||
| Type 2 Diabetes Mellitus | |||
| Hypertension | Monitor heart rate | Monitor BP and heart rate (Contraindicated in uncontrolled hypertension) | |
| Cardiovascular Disease - Coronary Artery Disease | Monitor heart rate | Monitor heart rate, BP | |
| Cardiovascular Disease - Arrhythmia | Monitor heart rate, rhythm | Monitor heart rate, rhythm, BP | |
| Cardiovascular Disease - Congestive Heart Failure | Insufficient data | Insufficient data | Insufficient data |
Chronic Kidney Disease -Mild (50–79 mL/min) | |||
| Chronic Kidney Disease - Moderate (30–49 mL/min) | Do not exceed 7.5 mg/46 mg per day | ||
| Chronic Kidney Disease - Severe (<30 mL/min) | Watch for oxalate nephropathy | Monitor urinary clearance of drug | Monitor urinary clearance of drug |
| Nephrolithiasis | Calcium oxalate stone | Calcium phosphate stones | |
| Hepatic Impairment - Mild-Moderate (Child-Pugh 5–9) | Watch for cholelithiasis | Do not exceed 7.5 mg/46 mg per day | Do not exceed 8 mg/ 90 mg in AM |
Hepatic Impairment - Severe (Child-Pugh >9) | Not recommended | Not recommended | Not recommended |
| Depression | Avoid maximum dose: 15mg/92mg per day | Insufficient safety data Avoid in adolescents and young adults | |
| Anxiety | Avoid maximum dose: 15mg/92mg per day | ||
| Psychoses | Insufficient data | Insufficient data | Insufficient data |
| Binge Eating Disorder | Insufficient data Possible benefit based on studies with topiramate | Insufficient data, though possible benefit based on studies with bupropion Avoid in patients with purging or bulimia nervosa | |
| Glaucoma | Contraindicated, may trigger angle closure glaucoma | May trigger angle closure glaucoma | |
| Seizure Disorder | If discontinued, taper slowly | Bupropion lowers seizure threshold | |
| Pancreatitis | Monitor for symptoms | ||
| Opioid Use | Will antagonize opioids and opiates | ||
| Women of Reproductive Potential - Pregnancy | Use contraception and discontinue orlistat should pregnancy occur | Use contraception and discontinue phentermine/ topiramate ER should pregnancy occur; perform monthly pregnancy checks to identify pregnancy early due to a risk of cleft lip/palate | Use contraception and discontinue naltrexone ER/bupropion ER should pregnancy occur |
Women of Reproductive Potential - Breastfeeding | Not recommended | Not recommended | Not recommended |
| Age ≥65 years | Limited data available | Limited data | Insufficient data |
| Alcoholism/Addiction | Insufficient data Topiramate may exert therapeutic effects. | Avoid due to seizure risk and lower seizure threshold on bupropion | |
| Post-Bariatric Surgery | Insufficient data | Limited data available | Insufficient data |
Table 3
Weight Loss and Cardiovascular Effects of Oral AOMs3
| Attribute | Orlistat | Phentermine | Phentermine-topiramate | Naltrexone-bupropion |
|---|---|---|---|---|
| Time Point (months) | 12 | 6 | 12 | 12 |
| Mean Weight Change (%) | -10.2 | -6.1 | -10.9 | -6.1 |
| Mean Systolic Blood Pressure Change (mm Hg) | -6 | -6.4 | -2.9 | -1 |
| Mean LDL-C Change (%) | -9.4 | Not reported | -8.4 | -2 |
| Mean Waist Circumference Change (cm) | -9.6 | -6.6 | -10.9 | -6.2 |
| Common Adverse Effects | Oily fecal spotting (27%), flatus with discharge (24%), fecal urgency (22%), steatorrhea (20%), oily discharge (12%), increased defecation (11%) | Xerostomia (12%), insomnia (11%), headache (10%) | Paresthesia (20%), xerostomia (19%), constipation (16%), headache (11%) | Nausea (19%), constipation (18%), headache (18%), vomiting (11%), and dizziness (10%) |
A 2024 study evaluated the effectiveness of six anti-obesity medications (phentermine, phentermine/topiramate, liraglutide (an injectable AOM), naltrexone/bupropion, lorcaserin, and orlistat) over a 6-month period, focusing on weight loss outcomes and changes in body composition.10 The primary outcome was the achievement of at least 5% weight loss, while secondary outcomes included ≥10% weight loss and changes in BMI, waist circumference (WC), and body composition metrics.10
Overall, 64.4% of participants achieved at least 5% weight loss within 6 months.10 Phentermine had the highest success rate (87.2%), followed by lorcaserin (75%), phentermine/topiramate (67.7%), liraglutide (58.1%), orlistat (50%), and naltrexone/bupropion (35.3%) (P = 0.002).10 Phentermine consistently demonstrated significantly higher odds of achieving weight loss than the other AOMs at all time points (2, 4, and 6 months).10 When evaluating ≥10% weight loss, 30.2% of participants reached this threshold.10 In terms of body composition changes, there were significant reductions in body weight, BMI, and body fat mass (BFM) across all AOM groups, but no significant differences in waist circumference (WC), skeletal muscle mass (SMM), percentage body fat (PBF), or visceral fat area (VFA).10 Phentermine and phentermine/topiramate showed the greatest reductions in body weight and fat mass, aligning with prior studies.10 Lorcaserin, while effective, is no longer available due to its FDA withdrawal over cancer risk concerns.10
Initiating and Stopping Oral AOMs
Initiating Oral AOMs
The decision to start an AOM should be individualized, with healthcare providers weighing the risks and benefits based on the patient’s BMI, comorbidities, and treatment goals. Before prescribing, clinicians should establish clear treatment goals, ensure the patient understands the potential side effects, and emphasize adherence to lifestyle modifications, including diet, exercise, and behavioral changes.13 Patient preferences play a critical role in adherence, as poor tolerability can lead to discontinuation and loss of treatment effects. At every visit, providers should monitor weight loss progress and side effects, adjusting treatment as necessary.13
Evaluating Treatment Response and Stopping Rules
To assess effectiveness, treatment response should be evaluated at 12 weeks using the maintenance dose.13 If a patient does not achieve at least 5% weight loss at 12 weeks (or 4% at 16 weeks for liraglutide), the medication should be discontinued, and an alternative therapy should be considered. These “stopping rules” are recommended by the FDA to minimize unnecessary medication exposure and improve the risk-benefit profile.13 However, clinicians should also consider whether the full therapeutic dose was reached and whether behavioral and lifestyle interventions were sufficiently implemented, as medication alone is often insufficient for meaningful weight loss.13
Discontinuing Oral AOMs and Managing Weight Regain
When discontinuing AOMs, patients should be counseled that weight regain is expected, as most medications help sustain lower body weight rather than cure obesity.13 This reinforces the importance of ongoing lifestyle interventions and, in some cases, the need for long-term pharmacotherapy to maintain results. If weight regain occurs after discontinuation, providers should assess whether restarting pharmacotherapy or modifying the treatment plan is appropriate.13
The Role of Collaborative Practice Models in Obesity Treatment
Interprofessional teams collaborate and coordinate, emphasizing mutual respect, shared decision-making, effective communication, and collective accountability for patient outcomes. Because obesity is a complex, chronic disease, treatment should be multidisciplinary, incorporating physicians, pharmacists, dietitians, psychologists, and exercise specialists. Pharmacists play a crucial role in medication counseling, adherence monitoring, and identifying drug interactions, while dietitians provide personalized nutrition guidance to optimize weight loss. Behavioral therapists and psychologists help with habit formation, emotional eating, and motivational counseling, while exercise physiologists assist in developing safe and sustainable physical activity plans. This team-based approach enhances treatment adherence and long-term success by addressing the biological, psychological, and behavioral factors influencing obesity.
Access, Affordability, and Adherence Challenges
Access to AOMs remains a significant barrier for many patients in the United States. Medicare does not cover AOMs solely for obesity, and Medicaid coverage varies widely from state to state.3 Employer-sponsored insurance plans frequently exclude these medications, leaving many patients to pay out of pocket. High costs, even with discounts or coupons, often impede adherence. Clinicians can assist by advocating for coverage, facilitating prior authorizations, and exploring financial assistance programs.3 Despite their benefits, real-world studies show that adherence to AOMs is poor, often due to side effects, costs, or insufficient patient education.3
Summary
Oral AOMs play a critical role in the comprehensive management of obesity. They function through various mechanisms, and the selection of an appropriate AOM should be tailored to the patient’s characteristics, including BMI, comorbidities, medication safety profiles, potential contraindications, and obesity phenotype. Clinicians should also consider barriers such as access, affordability, and adherence to maximize treatment success.
Effective interprofessional collaboration—incorporating dietitians, psychologists, and exercise specialists—enhances long-term patient adherence and optimizes treatment outcomes. Regular follow-up is essential to assess weight loss progress, manage adverse effects, and reinforce the importance of lifestyle interventions alongside pharmacotherapy.
References
Garvey WT, Mechanick JI, Brett EM, et al. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY COMPREHENSIVE CLINICAL PRACTICE GUIDELINES FOR MEDICAL CARE OF PATIENTS WITH OBESITY. Endocr Pract. 2016;22 Suppl 3:1-203. doi:10.4158/EP161365.GL
Grunvald E, Shah R, Hernaez R, et al. AGA Clinical Practice Guideline on Pharmacological Interventions for Adults With Obesity. Gastroenterology. 2022;163(5):1198-1225. doi:10.1053/j.gastro.2022.08.045
Gudzune KA, Kushner RF. Medications for Obesity: A Review. JAMA. 2024;332(7):571-584. doi:10.1001/jama.2024.10816
Bray GA, Ryan DH. Update on obesity pharmacotherapy. Ann N Y Acad Sci. 2014;1311:1-13. doi:10.1111/nyas.12328
Xenical package insert. Accessed March 7, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020766s026lbl.pdf
Alli package insert. Accessed March 7, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2007/021887lbl.pdf
Adipex-p package insert. Accessed March 7, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/085128s065lbl.pdf
Qysymia package insert. Accessed March 7, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022580s021lbl.pdf
Contrave package insert. Accessed March 7, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/200063s000lbl.pdf
Song JE, Ko HJ, Kim AS. Comparison of the Efficacy of Anti-Obesity Medications in Real-World Practice. Drug Des Devel Ther. 2024;18:845-858. Published 2024 Mar 18. doi:10.2147/DDDT.S445415
Patel JP, Hardaswani D, Patel J, et al. Comparative Effectiveness of Semaglutide, Liraglutide, Orlistat, and Phentermine for Weight Loss in Obese Individuals: A Systematic Review. Cureus. 2025;17(3):e80321. Published 2025 Mar 10. doi:10.7759/cureus.80321
Krentz AJ, Fujioka K, Hompesch M. Evolution of pharmacological obesity treatments: focus on adverse side-effect profiles. Diabetes Obes Metab. 2016;18(6):558-570. doi:10.1111/dom.12657
Tak YJ, Lee SY. Anti-Obesity Drugs: Long-Term Efficacy and Safety: An Updated Review. World J Mens Health. 2021;39(2):208-221. doi:10.5534/wjmh.200010
DISCLAIMER
The information provided in this course is general in nature, and it is designed solely to provide participants with continuing education credit(s). This course and materials are not meant to substitute for the independent, professional judgment of any participant regarding that participant’s professional practice, including but not limited to patient assessment, diagnosis, treatment, and/or health management. Medical and pharmacy practices, rules, and laws vary from state to state, and this course does not cover the laws of each state; therefore, participants must consult the laws of their state as they relate to their professional practice.
Healthcare professionals must consult their employer, healthcare facility, hospital, or other organization for guidelines, protocols, and procedures to follow. The information provided in this course does not replace those guidelines, protocols, and procedures, but is for academic purposes only, and this course’s limited purpose is for the completion of continuing education credits.
Participants are advised and acknowledge that information related to medications, their administration, dosing, contraindications, adverse reactions, interactions, warnings, precautions, or accepted uses is constantly changing. Any person taking this course understands that such a person must make an independent review of medication information before any patient assessment, diagnosis, treatment and/or health management. Any discussion of off-label use of any medication, device, or procedure is informational only, and such uses are not endorsed hereby.
Nothing contained in this course represents the opinions, views, judgments, or conclusions of RxCe.com LLC. RxCe.com LLC is not liable or responsible to any person for any inaccuracy, error, or omission with respect to this course or course material.
© RxCe.com LLC 2026: All rights reserved. No reproduction of all or part of any content herein is allowed without the prior, written permission of RxCe.com LLC.
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