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How to Break Weight Loss Plateaus with Semaglutide

Written by Andrew Le, MD

UpdatedDecember 14, 2024

Weight loss is a challenging endeavor for many individuals struggling with obesity. While initial progress may seem promising, weight loss plateaus eventually set in due to metabolic adaptations and a natural decline in resting energy expenditure.

These plateaus can be incredibly frustrating and disheartening. Fortunately, new pharmacological options like semaglutide demonstrate unmatched efficacy in aiding weight loss and providing a breakthrough for long-term weight management.

This article explores the mechanisms underlying weight loss plateaus and details how semaglutide, a novel glucagon-like peptide-1 receptor agonist, can help overcome barriers and produce meaningful weight reduction.

🔑 Key Takeaways

  • Weight loss plateaus are normal and caused by metabolic adaptations like decreased metabolism and loss of muscle mass. Seeing plateaus as feedback instead of failure helps maintain motivation.
  • Weight loss is not linear - rapid drops typically occur early, then plateaus and slight increases happen despite calorie deficits. This contrasts with common misconceptions that can lead to yo-yo dieting.
  • Semaglutide is a peptide drug that mimics the hormone GLP-1. It helps with weight loss by enhancing insulin production, inhibiting glucagon, reducing appetite, and slowing digestion.
  • Semaglutide received FDA approval for diabetes in 2017 and weight loss in 2021 after successful clinical trials demonstrating significant weight reduction compared to placebo.
  • In trials, semaglutide led to over 15% weight loss after 2 years compared to only 2.6% with placebo. Over 77% of the semaglutide group lost at least 5% weight.
  • Semaglutide has shown superior weight loss efficacy compared to other drugs. In one study, semaglutide patients lost almost 15% body weight on average versus only 2.4% for placebo.
  • Using semaglutide requires consulting a doctor, gradual dosage increases, eventually reaching a 2.4 mg weekly maintenance dose, combining with lifestyle changes, and monitoring potential side effects.
  • Common side effects include dizziness, fatigue, gastrointestinal issues, headaches, and stomach problems. Those with certain medical histories should avoid semaglutide.

Definition and Causes of Weight Loss Plateaus

A weight loss plateau is a period where there is no change in weight despite continued efforts in dieting and exercising. Initially, during weight loss, a rapid drop in weight is common, primarily due to the body releasing energy from glycogen stores. Research indicates that weight loss plateaus typically occur after about 6 months of following a low-calorie diet.

Glycogen, found in muscles and the liver, is a carbohydrate partly made of water. When glycogen is burned for energy, it releases water, which leads to weight loss. However, this effect is temporary.

As weight loss progresses, muscle mass, which helps maintain metabolism, is also lost. This loss of muscle mass leads to a decline in metabolism, causing the body to burn fewer calories at a lighter weight than a heavier weight. This metabolic change can cause weight loss to stall, leading to a plateau when the calories burned equal the calories consumed​​.

Hitting a weight loss plateau can be a demoralizing experience. Individuals committed to weight loss programs often feel frustrated and discouraged when their progress halts, even though they adhere to their dietary and exercise plans. This frustration can lead to decreased motivation and effort, potentially resulting in weight regain.

Understanding that weight loss plateaus are a common and normal part of the weight loss journey is crucial. Instead of viewing plateaus as failures or obstacles, seeing them as feedback mechanisms or a normal part of the process can help maintain motivation and adjust strategies as needed​​.

Misconceptions and the Reality of Weight Loss

Many individuals new to weight loss believe the process is linear, expecting continuous weight reduction. However, weight loss typically occurs more rapidly in the early stages and then may plateau or even slightly increase despite maintaining a calorie deficit.

This misunderstanding can lead to frustration and the phenomenon of "yo-yo dieting," where individuals, after encountering a plateau, may regain weight due to their perception of the diet failing​​.

Adopting a more positive and empowering perspective on weight loss plateaus is beneficial. Plateaus should be viewed as guides and sources of feedback rather than signs of failure or obstacles. Recognizing that plateaus are a universal experience and a part of the long-term goal of maintaining weight loss can help individuals make more intentional and adaptive choices in their weight loss journey​​.

Pro Tip

Support networks for weight loss journeys offer diverse perspectives that can help you overcome obstacles. If you're struggling with a weight loss plateau or facing challenges, your support system can introduce fresh insights and strategies.

Semaglutide: An Overview

Semaglutide is a medication used for treating type 2 diabetes and for long-term weight management. It is a peptide similar to the hormone glucagon-like peptide-1 (GLP-1) but modified with a side chain.

It is available in different forms, including subcutaneous injection (Ozempic) and oral pill (Rybelsus) for diabetes, and under the brand name Wegovy for weight loss​​.

Now, let's explore the sections below for details regarding how semaglutide works and the process by which it was approved.

Mechanism of Action

As a glucagon-like peptide-1 receptor agonist, semaglutide mimics the action of GLP-1. It enhances insulin production, the hormone responsible for lowering blood sugar levels, and appears to promote the growth of pancreatic beta cells, which are crucial for insulin production and release.

Semaglutide also inhibits glucagon production, a hormone that increases glycogenolysis and gluconeogenesis. Importantly, it reduces food intake by decreasing appetite and slowing digestion in the stomach, thus reducing body fat​​.

Approval and Usage

Semaglutide underwent a series of clinical trials, culminating in significant regulatory approvals. In October 2017, following a unanimous FDA Advisory Committee approval, the injectable version (Ozempic) was approved for diabetes treatment in the US and later in other countries, including:

  • Canada
  • European Union
  • Japan
  • Australia

The oral version (Rybelsus) received US approval in September 2019, with EU approval in April 2020. The FDA approved a higher-dose version (Wegovy) for weight management in June 2021, followed by approval in the European Union in January 2022. These approvals mark a significant milestone in medication usage for diabetes and weight management​​.

Semaglutide in Breaking Weight Loss Plateaus

Various clinical trials have demonstrated Semaglutide's efficacy in aiding weight loss.

In the STEP 5 Trial, it assessed the efficacy of semaglutide for long-term treatment of adults with obesity or overweight with weight-related comorbidities. The mean change in body weight from baseline to week 104 was -15.2% in the semaglutide group versus -2.6% with placebo.

Also, 77.1% of participants in the semaglutide group achieved weight loss ≥5% from baseline at week 104, compared to 34.4% in the placebo group. The study concluded that semaglutide treatment led to substantial weight loss over 104 weeks​​.

Beyond its impressive weight loss effects, semaglutide has also demonstrated significant cardiovascular benefits. In patients with type 2 diabetes and established cardiovascular disease, semaglutide has been shown to reduce the risk of major adverse cardiovascular events (MACE) such as heart attack, stroke, or cardiovascular death. The SUSTAIN 6 trial found that once-weekly subcutaneous semaglutide reduced the risk of MACE by 26% compared to placebo over a 2-year period. This cardiovascular protection appears to be linked to semaglutide's ability to improve multiple cardiometabolic risk factors, including body weight, blood pressure, and blood sugar control. For individuals struggling with both obesity and cardiovascular disease, semaglutide offers a promising option to address these interrelated health concerns simultaneously.

Additionally, the STEP clinical trial program, including STEP 1 and 3 trials, showed significant weight loss in participants without type 2 diabetes using semaglutide. Average placebo-subtracted weight losses of 12.4% and 10.3% were seen with semaglutide 2.4 mg at week 68​​.

Compared to other weight loss methods and medications, semaglutide has shown superior efficacy. Against other weight loss drugs, Semaglutide has been more effective in reducing body weight compared to drugs like orlistat (fat absorption inhibitor), liraglutide (another GLP-1 receptor agonist), and phentermine-topiramate (appetite suppressant and seizure medication combo).

Patients on semaglutide have experienced significant weight loss, often surpassing that achieved with other medications. For example, in a study, participants on semaglutide lost, on average, 14.9% of their body weight compared to 2.4% with placebo​​.

How to Use Semaglutide for Weight Loss

Exploring the potential of Semaglutide for weight loss marks a promising step in managing obesity, but it requires careful consideration and guidance. Here's what you need to know to use it safely and effectively:

Medical Consultation

It's crucial to consult a healthcare professional before starting Semaglutide. A doctor experienced in obesity management can assess your health profile, discuss potential risks or contraindications, and determine the appropriate dosage of Semaglutide shots. This step is important to ensure the treatment is safe and suitable for your health needs.​

Dosage and Administration

For the initial dose escalation schedule:

  • Weeks 1-4: 0.25 mg subcutaneously once a week.
  • Weeks 5-8: 0.5 mg subcutaneously once a week.
  • Weeks 9-12: 1 mg subcutaneously once a week.
  • Weeks 13-16: 1.7 mg subcutaneously once a week.

The maintenance dose of Semaglutide for weight loss begins from week 17 onward, at which point the dosage is set at 2.4 mg and administered subcutaneously once a week. However, there are considerations for dose adjustment based on individual tolerance.

If a patient finds the dose escalation to 2.4 mg challenging, it is advisable to delay it for an additional four weeks. Should the maintenance dose of 2.4 mg still prove difficult to tolerate, it can be temporarily reduced to 1.7 mg once a week for a maximum of four weeks. After this period, an attempt to increase the dose back to 2.4 mg should be made.

If the patient continues to experience intolerance at this maintenance dose, discontinuation of the therapy is recommended.

Combining with Lifestyle Changes

Combining Semaglutide with dietary changes, physical activity, and lifestyle modifications is essential for successful weight management. This includes:

  • Creating a personalized diet plan with a registered dietitian.
  • Implementing a regular exercise regimen, including aerobic exercises and strength training.
  • Lifestyle modifications include improving sleep quality, managing stress, and adopting healthier habits.
  • Ensuring medication adherence to the prescribed Semaglutide regimen.
  • Regular check-ins with your healthcare team to monitor progress and make necessary adjustments.
  • Seeking support and accountability from friends, family, or support groups​​.

Potential Side Effects

Common side effects include:

  • Dizziness
  • Fatigue
  • Gastrointestinal issues (such as diarrhea, constipation, and gassiness)
  • Headache
  • Stomach issues (including nausea, vomiting, pain, or distension)

Gastrointestinal issues are the most common complaint, especially when starting Semaglutide. Semaglutide side effects may be reduced by beginning on a lower dose and slowly increasing the amount taken​​.

🩺 Doctor’s Note

Regular monitoring and consultation with a healthcare provider are advised for long-term use to manage any potential side effects and adjust the treatment as needed.

Semaglutide should be avoided by individuals with a history of medullary thyroid cancer, gallbladder disease, pancreatitis, or multiple endocrine neoplasia syndrome type 2 (MEN2). Discussing your medical history with your doctor before starting Semaglutide is important.​​

Final Words

Semaglutide is a promising weight-loss breakthrough, enabling patients to overcome frustrating plateaus. Through appetite reduction and enhanced insulin production, robust clinical trials have demonstrated that Semaglutide achieves over 15% weight reduction over 2 years - far beyond other medications or lifestyle changes alone.


Under medical guidance, it offers long-term obesity treatment combined with dietary, exercise, and behavioral modifications.

FAQs on Semaglutide for Weight Loss

Is a calorie deficit still important when plateaued on semaglutide?

Yes, maintaining a calorie deficit is key. Semaglutide suppresses appetite, so you may need to track calories closely to ensure you remain deficient.

How often should I re-evaluate my semaglutide dose for plateaus?

Reassess your dose with your doctor every 3 months. Upping the dose by 0.25 or 0.5 mg if plateaued for 4+ weeks can improve weight loss.

How long should I wait before taking action on a plateau?

Wait at least 4 weeks without changing the scale before making diet and exercise changes to get past the plateau. Short-term fluctuations are normal.

What else can I do to break through a weight loss plateau?

Make sure you are tracking calories accurately, reducing your calorie intake by 100-200 per day, increasing protein intake to stay full on fewer calories, and strength training to build muscle and boost metabolism.

When should I consider prescription plateau breakers like phentermine?

If making diet, exercise, and dose changes for 8+ weeks still results in a plateau, ask your doctor about adding short-term prescription plateau breakers like phentermine to get lost again.

How can I get prescribed semaglutide for weight loss?

Talk to your doctor about whether you are a candidate for semaglutide. They will review your BMI and weight-related medical conditions to determine if a prescription is appropriate. If you are obese with a BMI over 30 or overweight with conditions like diabetes, your doctor may prescribe semaglutide for chronic weight management. Come prepared to discuss your weight loss efforts and goals.

What is the typical semaglutide dose for weight loss?

The recommended starting dose is 0.25 mg, injected subcutaneously once weekly. If the lower doses are well-tolerated, the dose can then be increased to 0.5 mg and eventually to 1 mg or 2 mg once weekly. Higher doses between 1-2 mg per week tend to provide better weight loss effects than lower 0.25-0.5 mg doses but may increase gastrointestinal side effects. Work closely with your doctor on dose adjustments.

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