GLP-1 Agonists for Weight Loss: Do they Work?

Among the GLP-1 agonists, several have garnered attention for their ability to aid in weight management. Ozempic, Wegovy, Moujaro, Rybelsus, Victoza, Trulicity, and Saxenda have demonstrated efficacy in promoting weight loss when used as part of a comprehensive treatment plan.

The Science of GLP-1 Agonists For Weight Loss ‍

GLP-1 agonists for weight loss work by mimicking the actions of a naturally occurring hormone, GLP-1, which is primarily secreted in the intestines after eating. This hormone serves several essential functions. One key role is its ability to stimulate the pancreas to release insulin, a hormone that helps regulate blood sugar levels. Insulin promotes the uptake of glucose from the bloodstream into cells for energy. However, the relevance of GLP-1 agonists in the context of weight management stems from their actions on appetite control and digestion.

When GLP-1 agonists for weight loss are introduced into the body, they engage with specific receptors in the brain, particularly the hypothalamus. This interaction triggers a feeling of fullness and satisfaction, reducing appetite wherein it creates an environment where weight loss becomes achievable. The exact mechanisms are complex and involve interactions with various brain circuits and hormones, but the net effect is a shift toward a more favorable energy balance, with the body burning more calories than it consumes.

Ozempic and Wegovy

Ozempic and Wegovy, although identical in their core medication, bear distinct brand names, each featuring varying concentrations of semaglutide and distinct FDA approvals. Initially introduced as Ozempic in 2017, the medication was primarily approved to address type 2 diabetes. Notably, in 2021, the FDA granted approval for the same drug to be marketed as Wegovy, specifically designed for weight loss. It's common for healthcare providers to prescribe both variants for weight management, yet several notable distinctions set them apart in their applications.

Ozempic has received FDA approval for the following purposes:

• Regulating blood sugar levels in adults aged 18 and older who have type 2 diabetes
• Mitigating the likelihood of significant cardiovascular issues, including heart attack, stroke, and mortality, in adults with both type 2 diabetes and pre-existing heart disease.

On the other hand, Wegovy has secured FDA approval for the long-term management of weight concerns in individuals aged 18 and above who meet either of the following criteria:

• Obesity, characterized by a body mass index (BMI) of 30 kg/m² or higher.
• Overweight, indicated by a BMI of 27 kg/m² or higher, provided they also have at least one weight-related medical condition, such as type 2 diabetes, high blood pressure (hypertension), or elevated cholesterol levels.

Wegovy typically involves a higher maintenance dose compared to Ozempic to achieve greater weight loss effects. While Ozempic options include 0.25 mg, 0.5 mg, 1.0 mg, and 2 mg strengths, Wegovy provides a broader range with 0.25 mg, 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg single-use pens. This means Wegovy allows for a higher dose than Ozempic, although a gradual escalation over five months is necessary. If deemed appropriate, your healthcare provider may raise your Ozempic dosage to a maximum of 2 mg weekly for blood sugar management.

Another significant contrast between Ozempic and Wegovy lies in the administration of their pens. When using Wegovy, each injection pen is equipped with an integrated needle. Following a single use, the entire pen is discarded into a sharps container. In contrast, Ozempic provides separate needles that require attachment to the injector pen before each dose. After each use, the needle is disposed of in a sharps container, while the same pen can be reused for multiple doses.

Mounjaro and Zepbound (Tirzepatide) ‍

Tirzepatide, the generic name for Mounjaro and Zepbound, is distinguished as the first and only of its kind to activate both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) hormone receptors. In March 2022, it was first approved as Mounjaro for the treatment of type 2 diabetes. This medication garnered considerable interest as a solution for individuals dealing with obesity. Although Mounjaro is only FDA-approved to treat diabetes, it is often prescribed off-label for weight loss.  

The effectiveness of Mounjaro in supporting weight loss has been substantiated through rigorous clinical trials. These trials have consistently shown that individuals using Mounjaro experience significant loss in body weight. In some cases, weight loss results have approached levels previously only seen with bariatric surgery. Notably, many participants have witnessed substantial improvements in their weight, often exceeding 20% of their initial body weight.

Mounjaro appears to be even more effective than Wegovy and Ozempic. In Eli Lilly's SURMOUNT-3 and SURMOUNT-4 clinical trials, participants administered tirzepatide achieved remarkable results with a weight loss of 21.1% over 12 weeks, culminating in a substantial mean weight reduction of 26.6% over 84 weeks.

Conversely, Novo Nordisk's SUSTAIN 7 and SUSTAIN FORTE clinical trials demonstrated that individuals using Ozempic experienced weight loss ranging from 9.3 to 14.1 pounds. On average, Ozempic users achieved a weight loss of approximately 15% of their initial body weight after 68 weeks, as reported in clinical trial results published in The New England Journal of Medicine.

Meanwhile, in November 2023, the FDA has approved the Zepbound injection developed by Eli Lilly and Company. This Tirzepatide is indicated for use in adults with BMI classification of 27 and greater and weight-related medical conditions, such as hypertension, dyslipidemia, type 2 diabetes, obstructive sleep apnea, or cardiovascular disease. Zepbound is intended to aid in weight loss and management when used in conjunction with a reduced-calorie diet and increased physical activity.

It is worth to note that Zepbound should not be co-administered with other tirzepatide-containing products or any GLP-1 receptor agonist medications. Additionally, its safety and efficacy have not been studied in patients with a history of pancreatitis or those with severe gastrointestinal disease, including severe gastroparesis.

Oral semaglutide ‍

Rybelsus, also referred to as oral semaglutide, represents an alternative within the family of GLP-1 agonists for weight loss. Unlike its injectable counterparts, Rybelsus offers a convenient oral form for those seeking assistance in weight management. Currently, this medication has only been approved to address type 2 diabetes and is shown to have a modest weight loss effect of about 5% average weight loss. Rybelsus can be a suitable option for those seeking the benefits of GLP-1 agonists for weight loss while prioritizing an oral form of medication over injections. However, in comparison to its subcutaneous injection counterparts, it exhibits a comparatively lower level of effectiveness.

Currently, oral semaglutide is also being studied in clinical trials at much higher doses than Rybelsus (50 mg vs 14 mg). Early studies show that high-dose oral semaglutide can result in weight loss comparable to the injection form of semaglutide (about 15% weight loss). Novo Nordisk has shared that they plan to submit oral semaglutide for approval as a weight loss drug, but it will still be some time before that comes to pass. For now, most providers are prescribing other medications for weight loss, including injectable GLP-1 medications

Trulicity

Trulicity, also known as dulaglutide, is a long-acting, injectable GLP-1 agonist designed for the management of type 2 diabetes. Trulicity's role extends beyond blood sugar control; it has also demonstrated noteworthy effectiveness in supporting weight loss.  

Clinical evidence showcases Trulicity's ability to facilitate weight loss. People with diabetes who integrate Trulicity into their treatment regimen frequently experience notable loss in body weight (about 5-10%) though more modest than with Ozempic, Wegovy, and Mounjaro.

Saxenda and Victoza

Saxenda and Victoza, also known as liraglutide, are noteworthy members of the GLP-1 agonist family though with the disadvantage of needing daily injections. While the medications have the same active ingredient, Victoza is only FDA-approved for diabetes while Saxenda can be given at a higher dose and approved as a weight loss medication.  

Similar to Trulicity, Saxenda can have a significant weight loss effect of about 5-10% body weight. However, the weight loss effect is still more modest than with Ozempic, Wegovy, and Mounjaro.

What are the side effects of GLP-1 Agonists For Weight Loss? ‍

Common side effects of GLP-1 agonists for weight loss typically involve mild gastrointestinal discomfort, such as nausea, vomiting, and diarrhea. These effects tend to be transient and manageable as the body adjusts to the medication. It is essential to start these medications at low doses and very gradually increase under the supervision of an experienced physician to minimize side-effects. GLP-1 agonists for weight loss should not be taken during pregnancy. In addition, they should not be taken in patients with a personal history of pancreatitis or a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia 2A or 2, given the possibility of pancreatitis and thyroid tumors. However, the overwhelming majority of users experience these medications without significant issues.

Comparing GLP-1 Agonists for Weight Loss ‍

When considering GLP-1 agonists for weight loss, it's essential to evaluate their effectiveness. Research has shown that all these medications can lead to significant weight loss. The extent of weight loss may vary from person to person. However, clinical trials and real-world data have consistently demonstrated that these medications often result in substantial decreases in body weight. This underlines the potency of GLP-1 agonists in helping individuals achieve healthier weights.

Selecting suitable GLP-1 agonists for weight loss depends on individual needs, preferences, cost, and medical considerations. Factors such as the presence of diabetes, specific weight loss goals, and an individual's response to each medication may influence the choice. Healthcare professionals play a crucial role in guiding patients toward the right medication, assessing benefits against risks, and ensuring ongoing monitoring for safety and effectiveness. Making an informed decision requires a comprehensive evaluation of the individual's unique health circumstances and treatment objectives.

New GLP-1 Medications on the Horizon

As the field of weight management and diabetes continues to advance, several promising GLP-1 agonists for weight loss are on the horizon. One noteworthy newcomer is Retatrutide, a groundbreaking medication that stands out as a triple-hormone agonist, including a GLP-1, GIP and glucagon. Early studies have shown weight loss benefits as high as 24% This multifaceted approach aims to target not only weight management but also diabetes control and other health-related concerns through a combination of mechanisms.

Meanwhile, high-dose oral semaglutide is also expected to be FDA-approved for weight loss soon. Unlike Rybelsus, which is FDA-approved for diabetes and comes at a lower dose, high-dose oral semaglutide can be as effective as injectable semaglutide while offering a notable advantage that it can be taken orally, eliminating the need for injections. This presents an attractive option for individuals who prefer the convenience of oral administration without compromising on the efficacy of the medication.  

Integrating Medication into a Comprehensive Weight Loss Plan ‍

Amy Schumer's weight loss journey with Ozempic

The use of GLP-1 agonists for weight loss often entails the need for long-term treatment. This is because these medications, while highly effective in promoting weight loss, primarily work at a hormonal level by regulating appetite and increasing feelings of fullness. Consequently, when these medications are discontinued, the body's natural appetite control mechanisms may return to their previous state, potentially leading to increased caloric intake and weight regain.

This highlights the significance of concurrent lifestyle changes, as they play a pivotal role in sustaining the weight loss achieved with these medications. Incorporating healthier dietary choices, portion control, regular physical activity, and mindful eating practices is essential to secure the long-term benefits of GLP-1 treatment. In addition, while taking GLP-1 agonists for weight loss it’s important to participate in exercise and strength training to ensure you preserve muscle as you lose weight. By adopting this multifaceted approach and adhering to both medication and lifestyle changes, individuals can enhance their chances of maintaining a healthier weight over time and reap the full benefits of these medications.

Meanwhile, effective weight management with medication requires a collaborative effort with healthcare professionals. Their expertise is invaluable in determining the right medication for your specific needs, monitoring your progress, and adjusting treatment plans as necessary. Regular check-ins and open communication ensure that the medication aligns with your health goals and minimizes potential risks.

Bottomline

GLP-1 agonists for weight loss represent a scientific breakthrough in helping people achieve healthier body weights. Their effectiveness in promoting weight loss is well-documented, and they have provided hope to individuals facing the challenges of obesity and related health concerns. These medications offer a real opportunity for substantial weight loss and improved health. However, it's important to recognize that GLP-1 agonists for weight loss are not standalone solutions. Achieving and maintaining a healthier weight demands a comprehensive approach. This includes dietary changes, portion control, mindful eating, and regular physical activity. Medication should be viewed as a valuable tool within this broader strategy.

Collaboration with healthcare professionals is pivotal, as it ensures the safe and effective use of these medications and aligns treatment plans with individual needs and goals. Furthermore, setting realistic expectations and embracing gradual progress are fundamental for lasting success.

For those seeking sustainable weight loss results, consider enrolling in our online weight loss courses or consult with our board-certified physicians and dietitians available through Shapely. Our expertise in GLP-1 agonists for weight loss will be invaluable in your journey to a healthier you. So, let us help you achieve the best shape of you!