Introduction

Recent statistics indicate that 73% of U.S. adults are classified as overweight or obese, with nearly half actively trying to lose weight (1,2). Shedding excess weight and maintaining long-term results is no small feat. Making sustainable lifestyle changes over weeks, months, and years can be particularly challenging (3).

Adopting a nutrient-rich diet in appropriate portions and increasing physical activity are beneficial for both physical and mental health. Losing just 5-10% of body weight can lead to significant improvements in triglycerides, blood pressure, and blood sugar levels (4). However, even after implementing a healthier lifestyle, some individuals may still require additional weight loss support (3).

Fortunately, several FDA-approved medications are available for long-term weight management. Known as anti-obesity medications (AOMs) (5), these treatments can provide extra assistance when combined with healthy eating and regular exercise, as they are not as effective when used alone (3,4,5,6).

Most AOMs require a prescription and are intended for individuals who have unsuccessfully attempted weight loss through diet and exercise alone. They are typically prescribed for those with a BMI of 30 or higher or a BMI of at least 27 with weight-related health conditions such as diabetes or hypertension (5,7).

The goal of these medications is to enhance weight management while maintaining a balanced diet and an active lifestyle (7). When combined with healthy habits, AOMs can increase weight loss by an additional 3-12% beyond lifestyle changes alone (4,7). However, they are not recommended for individuals who are pregnant, breastfeeding, or planning to conceive (7).

Understanding Anti-Obesity Medications and Their Mechanisms

A variety of long-term weight loss medications are available, but no single option is universally effective. The best choice depends on individual health status, current medications, family history, cost considerations, and potential side effects. Consulting a healthcare provider is essential for determining the most suitable option.

According to the Obesity Medicine Association, “All weight loss medications work best in the context of a healthy eating plan and exercise.” These medications function in various ways, including reducing hunger, increasing satiety, and decreasing cravings by interacting with hormones (e.g., leptin, ghrelin), neurotransmitters (e.g., GABA, serotonin), and peptides (e.g., GLP-1) in the brain, digestive system, and adipose tissue. By enhancing feelings of fullness and reducing caloric intake, these mechanisms facilitate weight loss (5,6,7).

Orlistat, however, operates differently by altering fat absorption in the digestive system (7).

Overview of Common Weight Loss Medications

Semaglutide, Tirzepatide, and Liraglutide

Semaglutide and tirzepatide are weekly injections that target brain regions regulating appetite and food intake. Semaglutide is a GLP-1 receptor agonist, while tirzepatide acts as a dual GLP-1 and GIP receptor agonist. Treatment begins with a low dose, gradually increasing over 16-20 weeks to minimize side effects such as digestive discomfort, headaches, dizziness, and fatigue (4,5).

Liraglutide, a daily injection, modulates gut hormones to promote satiety and reduce hunger (5).

Naltrexone-Bupropion

This oral medication combines an antidepressant with an opioid receptor antagonist. Together, they influence the brain’s pleasure-reward system, reducing appetite and cravings (4,5).

Phentermine and Phentermine-Topiramate

Phentermine, one of the oldest and most widely used weight loss medications, is an appetite suppressant. When combined with topiramate, a medication used for seizures and migraines, it further reduces hunger and cravings (4,5).

Orlistat

Orlistat differs from other AOMs by inhibiting fat absorption (5). Available in prescription and lower-strength over-the-counter forms, it is taken with meals and reduces dietary fat absorption by approximately 30% (8). However, undigested fats can cause gastrointestinal side effects such as loose stools and increased gas.

Potential Side Effects of Weight Loss Medications

When used as prescribed, these medications are generally safe, though mild side effects are common and often improve with continued use (4,6). The most frequently reported issues involve digestive discomfort, including nausea, constipation, and diarrhea (7,8). Other possible side effects include dry mouth, abdominal pain, vomiting, headaches, dizziness, nervousness, insomnia, and fatigue (5,7,8).

With orlistat, unabsorbed fats traveling through the digestive system can result in gastrointestinal disturbances (4,7). Additionally, individuals may regain some weight upon discontinuing AOMs due to metabolic adaptations, including changes in resting metabolic rate and hunger-regulating hormones (4,5,7,8). The Mayo Clinic emphasizes that maintaining healthy lifestyle habits is key to minimizing weight regain (7).

Regular follow-ups with a healthcare provider are crucial when taking anti-obesity medications. Monitoring progress, discussing side effects, and adjusting treatment as needed ensures the best possible outcomes.

Nutrition Considerations When Taking Weight Loss Medications

The most important thing to consider when taking any of these weight loss medications is to maintain a nutritious diet. This means that you’re getting all of the essential nutrients and eating the optimal quantities of food to help you reach your weight loss goals. Avoid weight loss programs that have too many unrealistic promises (1). 

According to the National Institute of Diabetes and Digestive and Kidney Diseases, a safe and successful weight loss program includes “a healthy, reduced-calorie eating and drinking plan, a plan for increasing physical activity if appropriate, guidance and support for adopting these lifestyle habits, and a plan for keeping the weight off” (1). 

The purpose of a good weight loss program is to set realistic weight loss goals, promote healthy long-term behaviors, and provide techniques to track progress and overcome barriers (1). Ideally, all of the elements listed above would be tailored to your specific situation by a healthcare professional such as a Doctor of Clinical Nutrition like myself.. 

While there is no one-size-fits-all weight loss program, there are some important nutritional guidelines to keep in mind when working toward losing weight:

A well-balanced, nutrient-dense diet is essential when using AOMs. A successful weight management plan should include:

• A realistic goal of losing approximately one pound per week (9)
• High-fiber foods such as fruits, vegetables, and whole grains (9)
• Lean protein sources and low-fat dairy products (9)
• Minimizing processed and high-sugar foods (8,9)
• Proper portion control (8,9)
• Choosing water as the primary beverage (9)
• Regular physical activity (9)

For those taking orlistat, additional dietary considerations include:

• Taking a multivitamin to counteract reduced absorption of fat-soluble vitamins (8)
• Consuming a lower-fat diet to minimize gastrointestinal side effects (5)

Read more about Nutrition Strategies for GLP-1 Medications and 6 Meal-Planning Mistakes Sabotaging Your Nutrition Goals.

Final Thoughts

As the Mayo Clinic states, “Weight-loss drugs aren’t an easy answer to weight loss. But they may help you make the lifestyle changes that you need to practice to lose weight and improve your health” (7).

If you need guidance on sustainable weight loss—whether with or without AOMs—working with a credentialed nutrition professional can provide valuable support.

Join our Sky Wellness Collective – a welcoming online community designed to provide guidance, motivation, and personalized support as you work toward your health goals. Whether you’re looking for advice on nutrition, lifestyle changes, or simply a place to connect with others who understand your journey, we’re here to help.

Join us today and take the next step toward achieving lasting health and wellness. Together, we can create a plan that works for you!

References

1. National Institute of Diabetes and Digestive and Kidney Diseases. (2024, February). Choosing a safe & successful weight-loss program. U.S. Department of Health and Human Services, National Institutes of Health. Retrieved January 14, 2025, from  https://www.niddk.nih.gov/health-information/weight-management/choosing-a-safe-successful-weight-loss-program

2. National Center for Health Statistics. (2018, July 12). Attempts to lose weight among adults in the United States, 2013–2016. Centers for Disease Control and Prevention. Retrieved January 14, 2025, from https://www.cdc.gov/nchs/products/databriefs/db313.htm

3. Mayo Clinic. (2023, November 1). Weight loss basics. Retrieved January 14, 2025, from https://www.mayoclinic.org/healthy-lifestyle/weight-loss/basics/weightloss-basics/hlv-20049483

4. National Institute of Diabetes and Digestive and Kidney Diseases. (2024, June). Prescription medications to treat overweight & obesity. U.S. Department of Health and Human Services, National Institutes of Health. Retrieved January 14, 2025, from https://www.niddk.nih.gov/health-information/weight-management/prescription-medications-treat-overweight-obesity

5. Obesity Medicine Association. (2024, January 26). Top weight loss medications. Retrieved January 14, 2025, from  https://obesitymedicine.org/blog/weight-loss-medications/

6. Cleveland CliniTop Weight Loss Medications | Obesity Medicine Associationc. (2023, November 20). Appetite suppressants. Retrieved January 14, 2025, from https://my.clevelandclinic.org/health/treatments/9463-appetite-suppressants

7. Mayo Clinic. (2022, October 29). Prescription weight-loss drugs. Retrieved January 14, 2025, from https://www.mayoclinic.org/healthy-lifestyle/weight-loss/in-depth/weight-loss-drugs/art-20044832

8. Medline Plus. (2023, July 8). Weight-loss medicines. U.S. Department of Health and Human Services, National Institutes of Health. Retrieved January 14, 2025, from https://medlineplus.gov/ency/patientinstructions/000346.htm

9. Johns Hopkins Medicine. (n.d.). Medical nutrition therapy for weight loss. Retrieved January 14, 2025, from https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/medical-nutrition-therapy-for-weight-loss