Injectables in Weight Loss Management Materials

TARGETED TREATMENT: THE ROLE OF INJECTABLES IN WEIGHT LOSS 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, a 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.

Topic Overview:

Injectable anti-obesity medications (AOMs) offer a novel approach to obesity management by targeting neurohormonal pathways to achieve sustained weight loss and improve metabolic health. Agents like liraglutide, semaglutide, and tirzepatide have demonstrated significant efficacy in clinical trials, with benefits including cardiometabolic risk reduction and treatment of sleep apnea. Incorporating AOMs into a comprehensive treatment plan that includes

dietary, physical, and behavioral interventions is essential for optimizing outcomes. This educational activity will explore the mechanisms, efficacy, and safety profiles of injectable AOMs, emphasizing their integration into a comprehensive obesity treatment framework. This course will also discuss the role of interprofessional collaboration in delivering patient-centered obesity care for patients utilizing these medications.

Accreditation Statement

RxCe.com LLC is accredited by the Accreditation Council for Pharmacy Education (ACPE) as a provider of continuing pharmacy education.

Universal Activity Number (UAN): The ACPE Universal Activity Number assigned to this activity is 

Pharmacist  0669-0000-25-057-H01-P

Pharmacy Technician  0669-0000-25-058-H01-T

Credits: 2 contact hour(s) (0.2 CEU(s)) of continuing education credit

Type of Activity: Knowledge

Media: Internet/Home study Fee Information: $6.99

Estimated time to complete activity: 2 contact hour(s) (0.2 CEU(s)), including Course Test and course evaluation

Release Date: May 12, 2025 Expiration Date: May 12, 2028

Target Audience: This educational activity is for pharmacists and pharmacy technicians.

Secondary Audiences: This educational activity is also for other healthcare professionals, such as nurses, physicians, or others who may be part of a healthcare team and may be interested in this educational topic. A healthcare team approach to patient care may be discussed in this activity, as applicable. No state board or professional organization has evaluated this activity to determine whether it meets the continuing education requirements of nurses, physicians, or other professions not listed under the “Target Audience” described above. Always verify with individual employers or supervisors whether they will accept this educational activity upon completion.

How to Earn Credit: From May 12, 2025, through May 12, 2025, participants must:

Read the “learning objectives” and “author and planning team disclosures;”

Study the section entitled “Educational Activity;” and

Complete the Course Test and Evaluation form. The Course Test will be graded automatically. Following successful completion of the Course Test with a score of 70% or higher, a statement of participation will be made available immediately. (No partial credit will be given.)

Credit for this course will be uploaded to CPE Monitor®.

Learning Objectives: Upon completion of this educational activity, participants should be able to:

Compare and Contrast available injectable anti-obesity medications (AOMs)

Evaluate the efficacy and safety of injectable AOMs

Describe how to incorporate injectable therapies into comprehensive weight loss plans

Counsel patients on the use of injectable AOMs

Disclosures

The following individuals were involved in developing this activity: L. Austin Fredrickson, MD, FACP, Liz Fredrickson, PharmD, BCPS, Susan Bowlin, DNP, FNP-BC, ACNP-BC, CBN, and Pamela Sardo, PharmD, BS. Austin Frederickson, Liz Frederickson, and Pamela Sardo have no conflict of interest or financial relationship or commercial or financial support relevant to this activity to report or disclose in the development of this activity. Susan Bowlin is a member of the Speaker’s Bureau for Eli Lilly and Novo Nordisk. Any potential conflicts of interest were mitigated.

© RxCe.com LLC 2025: 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

Targeted Treatment: The Role of Injectables in Weight Loss Management

Introduction

Injectable anti-obesity medications (AOMs) offer a transformative approach to obesity management. However, their use does require careful patient selection and regular monitoring to optimize outcomes and manage side effects. This educational activity will explore the mechanisms, efficacy, and safety profiles of injectable AOMs, emphasizing their integration into a comprehensive obesity treatment framework. This course will also discuss the role of interprofessional collaboration in delivering patient-centered obesity care for patients utilizing these medications.

A Paradigm Shift in Treatment Guidelines for Obesity

Within the past few years, guidelines for treating obesity have significantly changed focus.1-5 Newer guidelines reflect a shift from treatments centered on achieving weight loss to an interprofessional collaborative approach that addresses patient-centered goals and targets the underlying causes of obesity.1-5 For example, the American Diabetes Association (ADA) created the Chronic Care Model, which is patient-centered and requires a close working relationship between the person with diabetes and the care team members involved in treatment planning.2

In addition, obesity treatments were previously viewed as temporary and would end when targeted weight loss was achieved. However, longer- term strategies are now recommended to support metabolic health and prevent relapse.1

Pharmacotherapy Treatment Guidelines for Obesity

Several organizations, including the American College of Cardiology/American Heart Association (ACC/AHA), the American Association of Clinical Endocrinology (AACE), the American Gastroenterological Association (AGA), and the ADA, provide recommendations reflecting this shift in focus, and discussing the use of pharmacotherapy in the treatment of obesity. (See Table 1).1-5 The Obesity Medicine Association (OMA) also publishes an Algorithm eBook annually for adult and pediatric patients.6,7 These guides are invaluable for clinicians treating obesity.

When consulting the guidelines, it is important to review the 2013 ACC/AHA/TOS and 2016 AACE/ACE guidelines, and then supplement them with the newer guidance that reflects the paradigm shift for clinicians and patients discussed above. When initiating pharmacologic therapy, it is essential to engage in shared decision-making conversations to ensure patients understand that these medications are part of a long-term strategy to support metabolic health and prevent relapse.8,9

Table 1

Guideline Recommendations for Starting Pharmacotherapy to Treat Obesity1-4

Obesity should be managed as a chronic, relapsing condition, not a short-term or episodic issue.8 The STEP 4 and SURMOUNT 4 trials highlight this clearly: patients who discontinued semaglutide and tirzepatide regained 11.6% and 14% of their body weight, respectively.8,9 In both studies, not only did weight return, but so did cardiometabolic risk factors, including increases in blood pressure, HbA1c, and cholesterol levels.9,10 These findings underscore the importance of continued treatment to maintain weight loss and broader health improvements.

Nutrient-Stimulated Anti-Obesity Medications

Among the most recent additions to the obesity treatment arsenal are the nutrient-stimulated AOMs, which mimic the metabolic actions of natural hormones such as glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon, and amylin.11 The actions of GLP-

1 include glucose-dependent stimulation of insulin secretion, reduction of gastric emptying, and reduction of the inappropriate secretion of glucagon during hyperglycemia.12,13 Other hormones, such as GIP, glucagon, and amylin, complement GLP-1 through unique mechanisms, including promoting fat metabolism, increasing energy expenditure, and enhancing satiety.11

Initially developed to treat type 2 diabetes, GLP-1 receptor agonists (RAs) have been of great interest not only due to their incretin effect but also notable cardiometabolic benefits, such as lowering blood pressure and reducing inflammation.11 The physiological effects of GLP-1 RAs are summarized in Table 2.13

Table 2

Physiological Effects of GLP-1 Ras13,14

The Food and Drug Administration (FDA) has approved three nutrient- stimulated AOMs: liraglutide, semaglutide, and tirzepatide. Table 3 provides a comparison of these medications.11,15-17

Table 3

Comparison of FDA-Approved Nutrient-Stimulated AOMs11,15-17

Liraglutide

Liraglutide was approved for obesity management in 2014 for adults and later in 2020 for adolescents aged 12 and older.11 Clinical trials, including the Satiety and Clinical Adiposity–Liraglutide Evidence (SCALE) trials, reported weight loss ranging from 3.4% to 6.1% over one year, with over 60% of participants achieving at least 5% weight loss.3,15,18 Additionally, liraglutide reduced waist circumference, systolic blood pressure, and LDL cholesterol levels.11,15,18 In patients with type 2 diabetes, higher doses of liraglutide (3.0 mg) were shown to cause significant weight loss and reductions in hemoglobin A1c.11 Liraglutide also demonstrated cardiovascular benefits, including a reduction in MACE. However, these findings are limited to patients with diabetes.11

Liraglutide is initiated at a dose of 0.6 mg subcutaneously once daily for one week, with a gradual increase of 0.6 mg/day at weekly intervals to a target dose of 3 mg once daily.15 If patients experience difficulty tolerating the increased dose during titration, dose escalation can be delayed by one additional week.15 Patients can remain on the maximum tolerated dose, even if it is less than 3 mg/day, provided their weight loss goals are achieved at that dose.15 Therapy effectiveness should be evaluated after 12 weeks at the maximum tolerated dose or 16 weeks after initiating treatment. If at least 4% to 5% of baseline body weight loss has not been achieved, discontinuation of liraglutide is recommended.15 There are no dosage adjustments needed for liver function.15 Liraglutide should be used cautiously in those with severe renal impairment, given a lack of data in this patient population.15

In the event of a missed dose, patients should be instructed to resume the once-daily regimen with their next scheduled dose without taking an extra dose or increasing the next dose.15 If more than three days have passed since the last dose, therapy should be restarted at 0.6 mg/day to minimize gastrointestinal symptoms, followed by dose escalation based on clinical judgment and the patient’s previous gastrointestinal tolerability.15

Common side effects include nausea (39%), diarrhea (21%), and constipation (19%), particularly during dose escalation.11,15 These effects are usually mild to moderate but may lead to discontinuation in some patients.11 Studies have found that adherence often decreases over time, with 17% adherence reported at 12 months.11 Liraglutide may be reasonable for patients with type 2 diabetes or when AOMs are not covered by insurance.11 However, care teams should recognize that Liraglutide’s daily dosing requirement and gastrointestinal side effects can lead to difficulties with medication adherence.11 Patients who want to limit the number of injections may want to avoid Liraglutide.

Semaglutide

Semaglutide was approved for chronic weight management in adults in 2021 and for adolescents aged 12 and older in 2022.16,19 Unlike liraglutide, it is dosed weekly, which can assist with patient adherence.11,15,16

With multiple semaglutide studies, 9% were aged 65-75, and 8% were 75 or older.8,20,21 In the SELECT trial, 30% were aged 65-75 and 8% were 75 or older.20 No difference in effectiveness was observed in these patients.20

The Semaglutide Treatment Effect in People with Obesity Program (STEP) trials demonstrated significant efficacy, with weight loss ranging from 6.2% to 14.8% at 68 weeks and over 85% of participants achieving at least 5% weight loss.8 Furthermore, semaglutide reduced waist circumference, systolic blood pressure, and LDL cholesterol levels while improving glycemic control in patients with type 2 diabetes.8,22 In the Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity (SELECT) trial, semaglutide was found to reduce major adverse cardiovascular events (MACE) by 20% in adults with cardiovascular disease and obesity.11,23 It has also shown promise in reducing heart failure symptoms and systemic inflammation in patients with preserved ejection fraction.6

Semaglutide is administered subcutaneously once weekly, with a gradual dose escalation over several months to minimize side effects.16 The dosing schedule begins with 0.25 mg once weekly for the first 4 weeks, increasing to 0.5 mg weekly during weeks 5 through 8.16 From weeks 9 through 12, the dose is increased to 1 mg weekly, followed by 1.7 mg weekly during weeks 13 through 16.16 The preferred maintenance dose is 2.4 mg weekly starting at week 17; however, if not tolerated, a maintenance dose of

1.7 mg weekly may be used.16 Patients unable to tolerate 1.7 mg weekly are typically advised to discontinue therapy, but some may continue on the highest tolerated dose if sufficient weight loss is achieved.16 Therapy may be discontinued if at least 5% of baseline body weight loss is not achieved within 3 months.16

If a patient misses a dose, they should be instructed to administer the next injection as soon as possible within 5 days, after which the regular weekly schedule should resume.16 If more than 5 days have elapsed, the missed dose should be skipped, and the next dose given at the regularly scheduled time.16 If two or more consecutive doses are missed, patients may resume the

previous dosing schedule or restart the dose adjustment schedule based on clinical judgment.16 No dose adjustments are needed for hepatic or renal function impairment.16

Semaglutide is associated with several gastrointestinal side effects, including nausea (44%), diarrhea (30%), and constipation (24%).11,15 These effects are generally transient but may continue; this is most common for constipation.11,16 A subgroup analysis of the SELECT trial revealed higher rates of hip and pelvic fractures in certain populations.24 Specifically, in women, the rates were 0.3% for semaglutide versus 0% for placebo, and in individuals 75 years and older, the rates were 1.3% for semaglutide versus 0.15% for placebo.24 However, these differences were based on small numbers of events.24

Patients should be counseled on dietary modifications, such as smaller portions and increased fiber intake to mitigate these issues.11,16 Given its robust efficacy in achieving sustained weight loss and broader metabolic benefits, semaglutide is particularly suited for patients with multiple weight- related conditions.11 However, adherence is crucial, as discontinuation often results in weight regain.11

Tirzepatide

Tirzepatide was approved for obesity treatment in 2023.11 It was also approved for treating obstructive sleep apnea (OSA), a comorbidity of obesity, in December 2024. This AOM leverages the complementary actions of GIP and GLP-1, enhancing appetite suppression and energy expenditure while improving glucose regulation.11,17 The SURMOUNT trials reported weight loss ranging from 11.6% to 21.4%, with over 90% of participants achieving at least 5% weight loss.11,25 Tirzepatide also significantly improved cardiometabolic outcomes, including reduced waist circumference, systolic blood pressure, and LDL cholesterol.11,25 Compared to semaglutide, tirzepatide has shown greater efficacy in weight reduction, making it an ideal choice for patients with severe obesity or those requiring substantial weight loss to

address comorbid conditions.11 However, ongoing cardiovascular outcome trials are needed to confirm its long-term safety and efficacy.11

Tirzepatide is used for weight management as an adjunct to diet and exercise in individuals with a BMI ≥30 kg/m² or a BMI ≥27 kg/m² with at least one weight-associated comorbidity, such as cardiovascular disease, dyslipidemia, hypertension, obstructive sleep apnea, or type 2 diabetes mellitus.17 The initial subcutaneous dose is 2.5 mg once weekly for the first 4 weeks, followed by an increase to 5 mg once weekly.17 Further dose escalation in 2.5 mg/week increments every 4 weeks may be considered as needed, up to a maximum weekly dose of 15 mg.11 The initial low dose of 2.5 mg is intended to minimize gastrointestinal side effects and does not contribute significantly to weight loss.17 The three maintenance dose options are 5 mg, 10 mg, and 15 mg.

In the event of a missed dose, it should be administered as soon as possible within 4 days, with the usual schedule resuming thereafter.11 If more than 4 days have elapsed since the missed dose, skip it and administer the next dose on the regular schedule.17 No dose adjustments are necessary for either impaired renal or hepatic function.17 If a woman is taking oral birth control, consider switching to a non-oral method of contraception or adding a barrier method of contraception after the initiation of Zepbound and for four weeks after each dose escalation

Common adverse effects are dose-dependent and include nausea (25%- 29%), diarrhea (19%-23%), and constipation (11%-17%), which occur mainly during dose escalation and are generally mild to moderate in severity.11,17 Counseling on dietary adjustments and gradual dose escalation can help mitigate these effects.11,17

Considerations for Use of Nutrient-Stimulated AOMs

When selecting a nutrient-stimulated AOM, the healthcare team should consider a patient’s individual goals, comorbidities, and potential tolerability issues, in addition to potential contraindications and drug-drug interactions.

Additionally, regular monitoring is essential to optimize outcomes and manage side effects effectively. A multidisciplinary approach ensures comprehensive management, addressing the complex needs of patients seeking weight loss. Before prescribing an injectable AOM for use by a patient, clinicians must consider the patient’s medical condition or population characteristics. These are summarized in Table 4.11

Table 4

Injectable AOMs Considerations based on Condition and Population11

GLP-1 RAs are contraindicated in patients with a personal or family history of medullary thyroid carcinoma or patients with multiple endocrine neoplasia syndrome type 2.14,16 They should also be used with caution in patients with a history of pancreatitis.14,16 In post-marketing reviews of these drugs, cases of both hemorrhagic and non-hemorrhagic pancreatitis have been noted.15,16 If pancreatitis occurs, the drug should be discontinued and not restarted.15,16 Tirzepatide is contraindicated in patients with a personal or family history of medullary thyroid cancer or Multiple Endocrine Neoplasia Syndrome type 2.17 Patients should be cautioned of the potential for acute pancreatitis and gallbladder disease.17 Precautions and drug interactions for these medications are summarized in Table 5.11

Table 5

Injectable AOM Precautions11

Patient Counseling Considerations Injection Technique

Proper injection technique is crucial to administering GLP-1 RAs and GIP-RAs to ensure effective treatment and patient safety.26 Each agent is associated with specific administration instructions.26 Proper injection techniques can minimize the risk of injection site reactions, increase medication absorption, and improve patient compliance.26

Storage

Storage recommendations for these medications vary by the type and brand, but generally, they should be stored in the refrigerator between 36°F and 46°F (2°C and 8°C) until their expiration date.15-17 Once opened, GLP-1 RAs and tirzepatide can be kept at room temperature (68°F to 77°F or 20°C to 25°C) for a specified period of time.15-17 Patients should be advised to check the expiration date before using their medication and to discard any expired medication. Additionally, they should be instructed to protect their medication from light, heat, and freezing temperatures.15-17

Cost Considerations

Access to insurance coverage for injectable AOMs is limited in the United States.27 Medicare does not typically cover AOMs for obesity alone, but may provide coverage when they are FDA-approved for treating obesity in conjunction with other conditions, such as semaglutide for cardiovascular risk reduction in individuals with obesity or overweight and preexisting cardiovascular disease.27 Tirzepatide may be covered by Medicare and commercial insurance for patients with moderate to severe obstructive sleep apnea (AHI > 15) with overweight or obesity.27 Medicare does cover some nutrient-stimulated hormone-based medications for managing type 2 diabetes. Medicaid coverage for AOMs is available in only a few states, and employer-sponsored health plans often exclude these medications. As a result, many patients must pay for AOMs out of pocket.27 While online discounts and coupons can reduce retail prices, Medicare beneficiaries are not eligible for manufacturer discounts.

Some drug manufacturers have a mail-order pharmacy with special pricing and coupons that Medicare patients may use. The prescription must be sent via the pharmacy’s Electronic Health Record system, and the medication is sent to the patient's home.28

Financial barriers may impact patients’ ability to begin or maintain treatment, and medical practices may need to dedicate staff resources to handle the prior authorization process required for determining insurance coverage. Table 6 provides a comparison of the costs of AOMs.

Table 6

Cost of Nutrient-Stimulated AOMs11

Compounding Concerns

Due to cost concerns, increased demand, and intermittent shortages of these medications, patients may seek to use compounded versions. In December 2024, the ADA issued guidance discouraging compounded GLP-1 RAs and dual GIP/GLP-1 RAs due to concerns about their content, safety, quality, and effectiveness, since they are not FDA-approved.29 The ADA highlighted the risks associated with the widespread availability of compounded versions of GLP-1 RA medications. Additionally, the FDA has received numerous reports of adverse events linked to compounded injectable semaglutide products, many of which involve dosing errors.30 These errors arise from patients self-administering incorrect doses and, in some cases, healthcare professionals miscalculating doses.30 Additionally, some adverse events occurred when compounded semaglutide or tirzepatide products were used in doses exceeding those recommended in the FDA-approved drug label, such as higher single doses, more frequent dosing, or accelerated titration schedules.30

Some compounded semaglutide products contain salt forms, such as semaglutide sodium or semaglutide acetate, which differ from the active ingredient in FDA-approved drugs.30 The FDA has no data confirming the safety, efficacy, or chemical equivalence of these salt forms and deems their use in compounding unlawful.30 As of November 2024, the FDA received over

392 reports of adverse events associated with compounded semaglutide.30 Further, the FDA is aware of counterfeit Ozempic circulating in the U.S., which may contain incorrect, insufficient, or harmful ingredients.30 These counterfeit drugs pose significant public health risks, and the FDA actively investigates such cases.30

Given these concerns, healthcare providers are urged to be cautious when prescribing compounded versions of these drugs and to ensure appropriate dosing and titration schedules.30 Adverse events or quality concerns related to compounded semaglutide, tirzepatide, or other medications to the FDA's MedWatch Adverse Event Reporting program. Reports can be submitted online or via fax.30

MC4 Receptor Agonists: Setmelanotide

Setmelanotide is approved for patients with genetically confirmed or suspected deficiencies in proopiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1), or leptin receptor (LEPR) and for Bardet-Biedl Syndrome (BBS).31 This drug targets genetic obesity syndromes by reducing hunger and slightly increasing energy expenditure.1 It is specialized for rare conditions linked to POMC, PCSK1, or LEPR deficiencies and offers significant weight loss in responsive patients.1,31 Its adverse effects, including injection site reactions and skin changes, necessitate close monitoring, particularly for depression or suicidal ideation. (See Table 7).1

Table 7

Setmelanotide Dosing, Administration, and Warnings1,31

Considerations for the Healthcare Team

A successful medical evaluation depends on beneficial interactions between the patient and the care team.2 Healthcare should be coordinated between the interprofessional team, including specialists, primary care, and subspecialty clinicians, nurses, registered dietitian nutritionists, exercise specialists, pharmacists, dentists, podiatrists, behavioral health professionals, and community partners such as community health workers and paramedics.2 Patients should also assume an active role in their care.2

Management plans begin with lifestyle changes but may then move into injectable medications for weight management.2 The team members should consider several key principles when using injectable medications. Obesity is a chronic disease, and pharmacotherapy should be part of a lifelong, comprehensive treatment plan that includes nutrition, physical activity, and behavioral counseling.32 The goals of obesity treatment extend beyond weight loss to include preventing, managing, and reducing complications of obesity.32 If body composition analysis equipment is available, trends in muscle mass and fat mass changes should be evaluated closely.

Patients should be counseled that discontinuation of injectable AOMs often leads to weight regain.32 Additionally, responses to AOMs vary significantly between individuals, ranging from no weight loss (non- responders) to greater than 25% total body weight loss, with average efficacy in trials spanning 5–23% weight loss.32 These considerations highlight the importance of individualized, long-term strategies in pharmacological weight management.32 Cross-disciplinary professionals may be recommended to optimize patient and family education for individuals seeking care. Cross- disciplinary education includes connections and intersections between different disciplines. This approach encourages professionals to seek insights and solutions from diverse fields, such as genetics, adolescent medicine, pediatrics, adult medicine, endocrinology, dietary, or psychiatric considerations.

Summary

Injectable AOMs offer a novel approach to obesity management by targeting neurohormonal pathways to achieve sustained weight loss and improve metabolic health. Agents like liraglutide, semaglutide, and tirzepatide have demonstrated significant efficacy in clinical trials, with benefits extending to cardiometabolic risk reduction. Incorporating AOMs into a comprehensive treatment plan that includes dietary, physical, and behavioral interventions is essential for optimizing outcomes. Regular monitoring and patient education are crucial to address side effects, ensure adherence, and mitigate risks associated with compounded or counterfeit medications. Collaborative care fosters personalized treatment strategies, supporting holistic, sustainable weight management.

Obesity should be managed as a chronic, relapsing condition, not a short-term or episodic issue. The STEP 4 and SURMOUNT 4 trials highlight this clearly: patients who discontinued semaglutide and tirzepatide regained 11.6% and 14% of their body weight, respectively. In both studies, not only did weight return, but so did cardiometabolic risk factors, including increases in blood pressure, HbA1c, and cholesterol levels. These findings underscore the importance of continued treatment to maintain weight loss and broader health improvements. This represents a paradigm shift for clinicians and patients, many of whom have traditionally viewed obesity treatment as temporary. As we initiate pharmacologic therapy, it is essential to engage in shared decision-making conversations to ensure patients understand that these medications are part of a long-term strategy to support metabolic health and prevent relapse.

Course Test

Which of the following injectable anti-obesity medications (AOMs) is matched to its correct dosing strategy?

Liraglutide: Begin at 0.6 mg daily; max dose 3 mg daily

Tirzepatide: Begin with 2 mg daily; max dose 3 mg daily

Semaglutide: Begin at 1 mg daily; max dose 3 mg daily

Setmelanotide: Begin at 0.25 mg weekly; max dose 2.4 mg weekly

Which injectable anti-obesity medication has the shortest half- life?

Liraglutide

Semaglutide

Tirzepatide

Setmelanotide

Which of the following is a common side effect among all nutrient-stimulated AOMs?

Hypertension

Hyperglycemia

Rash

Nausea

Which of the following is a crucial component of a comprehensive weight loss plan alongside injectable AOMs?

Eating a high-protein, low-fiber diet

Nutrition, physical activity, and behavioral counseling

Always combining injectable AOMs with oral AOMs

Intermittent fasting and minimizing exercise

Which of the following counseling points is important for patients experiencing nausea with GLP-1 RAs?

Skip doses until nausea resolves

Adjust portion sizes and increase fiber intake

Take antiemetic medication routinely

Avoid physical activity

What is a contraindication for GLP-1 RA use?

Personal or family history of medullary thyroid carcinoma

Hypertension

Severe hepatic impairment

Renal impairment

Which of the following has a notable side effect of skin hyperpigmentation?

Liraglutide

Setmelanotide

Tirzepatide

Semaglutide

A patient wants to utilize a nutrient-stimulating AOM but also wants to limit the number of injections. Which of the following AOMs would the patient probably want to avoid?

Tirzepatide

Setmelanotide

Liraglutide

Semaglutide

In which patient population should injectable, nutrient-stimulated AOMs be avoided?

Patients with severe hepatic impairment

Patients with a family history of breast cancer

Patients with hypertension

Patients with severe gastrointestinal disease

Which of the following is an important counseling point for patients utilizing injectable AOMs?

Injectable AOMs are almost always covered by insurance.

Compounded injectable AOMs have the same safety and efficacy data as the manufactured FDA-approved product.

Injectable AOMs should be stored in the freezer until their first use.

Gradual dose escalation can assist in minimizing GI side effects.

References

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Aronne LJ, Sattar N, Horn DB, et al. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. JAMA. 2024;331(1):38-48. doi:10.1001/jama.2023.24945

Kosiborod MN, Bhatta M, Davies M, et al. Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity: STEP 1 and 4 exploratory analyses. Diabetes Obes Metab. 2023;25(2):468-

478. doi:10.1111/dom.14890

Gudzune KA, Kushner RF. Medications for Obesity: A Review. JAMA. 2024;332(7):571-584. doi:10.1001/jama.2024.10816

Romera I, Cebrián-Cuenca A, Álvarez-Guisasola F, Gomez-Peralta F, Reviriego J. A Review of Practical Issues on the Use of Glucagon-Like Peptide-1 Receptor Agonists for the Management of Type 2 Diabetes. Diabetes Ther. 2019;10(1):5-19. doi:10.1007/s13300-018-0535-9

Psaltis JP, Marathe JA, Nguyen MT, et al. Incretin-based therapies for the management of cardiometabolic disease in the clinic: Past, present, and future. Med Res Rev. 2025;45(1):29-65. doi:10.1002/med.22070

Yang X, Qiang Q, Li N, Feng P, Wei W, Hölscher C. Neuroprotective Mechanisms of Glucagon-Like Peptide-1-Based Therapies in Ischemic Stroke: An Update Based on Preclinical Research. Front Neurol. 2022;13:844697. Published 2022 Mar 15.

doi:10.3389/fneur.2022.844697

Saxenda. Prescribing information. Novo Nordisk. November 2024. Accessed May 8, 2025. https://www.novo-pi.com/saxenda.pdf

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