Combining Wegovy with Lifestyle Changes: Best Practices for Doctors

Obesity is a chronic and complex disease that requires long-term strategies for effective management. Despite various treatments available, achieving sustained weight loss has been a challenge for many patients. On June 4, 2021, the U.S. Food and Drug Administration (FDA) announced the approval of Wegovy (semaglutide) injection, a new once-weekly injectable medication for weight management in adults. This new treatment has created a buzz in the medical community, offering a promising option for individuals struggling with obesity. In this comprehensive article, we will explore what Wegovy is, how it works, its effectiveness, safety profile, clinical trial results, potential side effects, comparison with other treatments, and guidelines for its use in clinical practice.

What is Wegovy (Semaglutide)?

Wegovy is a brand name for semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist initially approved for managing type 2 diabetes under the brand names Ozempic and Rybelsus. Unlike its previous formulations, Wegovy is specifically indicated for chronic weight management in adults who are obese (BMI ≥30) or overweight (BMI ≥27) with at least one weight-related comorbidity, such as hypertension, type 2 diabetes, or dyslipidemia. The drug is administered via a subcutaneous injection once a week, making it a convenient option for patients.

Mechanism of Action: How Does Wegovy Work?

Semaglutide, the active ingredient in Wegovy, mimics the GLP-1 hormone that targets areas of the brain involved in appetite regulation. GLP-1 receptor agonists work by:

• Reducing Appetite: Semaglutide slows gastric emptying, leading to a feeling of fullness that helps reduce calorie intake.
• Enhancing Satiety: It increases the feeling of satiety, meaning patients feel full sooner and stay full longer.
• Regulating Blood Sugar Levels: While primarily approved for weight management, semaglutide also reduces blood glucose levels, which is particularly beneficial for patients with type 2 diabetes.

These mechanisms collectively contribute to significant weight loss in individuals with obesity or overweight conditions, making it a dual-benefit drug.

Clinical Trials and Effectiveness

The approval of Wegovy was based on the results of the STEP (Semaglutide Treatment Effect in People with Obesity) clinical trial program, which included four Phase 3 trials involving over 4,500 participants across various demographics and comorbidities.

1. STEP 1 Trial: This trial involved 1,961 adults with a BMI of 30 or greater (or 27 or greater with at least one comorbidity). Participants were randomized to receive either Wegovy or a placebo, along with lifestyle intervention. After 68 weeks, the Wegovy group achieved an average weight loss of 14.9% compared to 2.4% in the placebo group.
2. STEP 2 Trial: Focusing on adults with type 2 diabetes, this trial demonstrated a weight reduction of 9.6% in the Wegovy group versus 3.4% in the placebo group over 68 weeks. This study underscores Wegovy's dual role in managing both weight and blood sugar.
3. STEP 3 Trial: This trial included 611 adults who were placed on a low-calorie diet and increased physical activity, alongside either Wegovy or a placebo. Participants on Wegovy lost 16% of their initial body weight, while those on the placebo lost only 5.7%.
4. STEP 4 Trial: In a withdrawal trial where participants were initially treated with Wegovy, those who continued the treatment after the first 20 weeks maintained their weight loss, while those switched to a placebo regained most of the weight.

The collective results from these trials indicate that Wegovy is highly effective for weight loss, achieving up to 20% weight reduction in some patients. These findings are significant as they demonstrate the efficacy of Wegovy in diverse populations, including those with type 2 diabetes and those without.

Safety and Side Effects

While Wegovy has proven to be effective for weight management, it is not without potential side effects. The most commonly reported side effects in clinical trials were gastrointestinal in nature, including:

• Nausea: Occurred in about 44% of participants but was generally mild to moderate and decreased over time.
• Diarrhea: Reported in about 30% of participants.
• Vomiting: Seen in approximately 24% of participants.
• Constipation: Reported in about 24% of participants.

Other less common but potentially serious side effects include pancreatitis, gallbladder disease, renal impairment, and an increased risk of thyroid C-cell tumors, as observed in rodent studies. Due to the latter, Wegovy carries a boxed warning and is contraindicated in patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).

Comparing Wegovy with Other Obesity Treatments

Several pharmacological options are available for weight management, each with its mechanism of action, efficacy, and safety profile. Commonly used treatments include:

• Liraglutide (Saxenda): Another GLP-1 receptor agonist, which requires daily injections. Wegovy, with weekly dosing and greater weight loss efficacy (15% vs. 8% on average), has a clear convenience and effectiveness advantage.
• Orlistat (Xenical, Alli): An intestinal lipase inhibitor that reduces fat absorption but is associated with significant gastrointestinal side effects. Wegovy is often better tolerated and more effective.
• Phentermine-Topiramate (Qsymia): A combination of a sympathomimetic amine and an antiepileptic drug that suppresses appetite. While effective, it has potential cardiovascular side effects, which makes Wegovy a safer alternative for many patients.
• Bariatric Surgery: The gold standard for long-term weight loss in patients with severe obesity. However, surgery carries significant risks, and not all patients are candidates. Wegovy provides a non-surgical alternative with meaningful weight loss results.

Guidelines for Use in Clinical Practice

When considering Wegovy for patients, healthcare providers should conduct a comprehensive assessment, including evaluating the patient's weight history, comorbid conditions, and readiness for pharmacotherapy. Here are key guidelines to consider:

1. Indications: Wegovy is approved for adults with a BMI ≥30 or ≥27 with at least one weight-related comorbidity. It is important to evaluate for contraindications, such as a history of medullary thyroid carcinoma or MEN 2.
2. Initiation and Dosing: Wegovy is initiated at a dose of 0.25 mg once weekly and gradually titrated over 16 weeks to the target dose of 2.4 mg weekly. This gradual increase helps to minimize gastrointestinal side effects.
3. Monitoring: Regular follow-up is essential to monitor weight loss, evaluate side effects, and make dose adjustments. Patients should be advised about potential side effects, especially gastrointestinal symptoms, and provided with strategies to manage them.
4. Lifestyle Modifications: Wegovy should be used in conjunction with a reduced-calorie diet and increased physical activity. The importance of a comprehensive lifestyle intervention cannot be overstated, as it enhances the drug's effectiveness and promotes long-term adherence.
5. Discontinuation Criteria: If a patient has not lost at least 5% of their body weight after 16 weeks on the target dose, the clinician should consider discontinuing Wegovy, as further treatment is unlikely to provide benefit.

The Future of Obesity Treatment

The approval of Wegovy marks a significant step forward in the pharmacological treatment of obesity. Its effectiveness, safety profile, and convenience of once-weekly dosing offer a compelling option for many patients who struggle with weight management. As research continues, the potential expansion of indications, including for younger populations or specific metabolic conditions, may further widen its applicability. Moreover, Wegovy's success may pave the way for the development of next-generation GLP-1 receptor agonists and combination therapies that offer even greater benefits.

Conclusion

Wegovy is a groundbreaking treatment for obesity that provides substantial weight loss for many patients when combined with lifestyle changes. Its approval by the FDA offers a new, effective, and well-tolerated option for adults struggling with weight management. As with any medication, it is vital for healthcare providers to assess each patient's individual needs, potential benefits, and risks, and to offer comprehensive care that includes pharmacological and non-pharmacological strategies for optimal outcomes.