The GLP-1 Weight Loss Promise: What the Studies Aren’t Telling You

Key Takeaways

• GLP-1 weight loss studies promise a reduction of 15 to 20% of body weight, but these results are often unrealistic in a real-world setting.
• Emerging real-world data indicate modest weight loss of 3 to 5% on average with GLP-1 medications. Responses to GLP-1s vary depending on the individuals, with some losing more weight than others. 
• Limited support and guidance, uncomfortable side effects, and the high cost of GLP-1 medications limit long-term adherence, impacting the real-world effects of the drug. 

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Glucagon-like peptide-1 (GLP-1) medicines such as semaglutide and tirzepatide have been hailed as game-changers for weight loss. Bold statements claim individuals can lose 15% or more of their body weight with these medications. 

If it sounds almost too good to be true, you may be on to something. In reality, the results are more nuanced. So, how do these numbers hold up in the real world? We analyze clinical studies and compare them to emerging real-world data to provide a more balanced view of what people can expect from GLP-1s.

Where That 15% Comes From

Two marquee studies reported significant weight loss of 15-20% with GLP-1 medications. 

1. Semaglutide Treatment Effect in People With Obesity (STEP): Weekly 2.4 milligram (mg) semaglutide injections resulted in an average weight loss of 14.9% after 68 weeks. Seventy percent of participants shed at least 10% of their body weight, half lost 15%, and one-third managed to lose 20% or more.¹ 
2. Study of Tirzepatide in Participants With Obesity or Overweight (SURMOUNT): Tirzepatide, which acts on two appetite-related hormones instead of one, produced dose-dependent weight loss results after 72 weeks: 15% at 5 mg, 19.5% at 10 mg, and 20.9% at 15 mg.²

These numbers exceed the clinical threshold of 5% or more, where markers such as glucose, blood pressure, and cholesterol typically improve. Impressive, right? But remember, clinical trials aren’t exactly real life. To understand why study results differ so vastly from the real world requires a closer look. 

How Study Design Inflates Results

GLP-1 weight loss studies occur in tightly controlled environments. Participants are carefully selected, coached, and closely monitored—hardly the reality of juggling work, kids, and a pharmacy bill. It’s no wonder weight loss results are exaggerated.

• Trials recruit highly screened participants: STEP and SURMOUNT recruited individuals with a BMI of 30 or greater, or a BMI of 27 or higher with at least one preexisting obesity-related condition. Many participants had higher starting weights, resulting in greater weight loss and improved outcomes.³ Trials prohibited anyone who had tried another GLP-1 medication within 90 days before the screening or had undergone or planned to have weight-loss surgery. The SURMOUNT trial also excluded volunteers who had experienced weight fluctuations of five kilograms or more within the past 90 days.^1,2 That weeds out more complex cases.
• Intensive lifestyle support is baked in. STEP and SURMOUNT trial participants underwent individual counseling sessions, followed a 500-calorie deficit diet, and logged 150 minutes of exercise weekly. Healthcare professionals reviewed food diaries and exercise logs to ensure accountability and adherence to a healthy, balanced diet.^1,2 Support is key for weight loss success, and participants were given access to professionals and resources with no additional effort or cost.
• Adherence is monitored. Providers schedule doses and troubleshoot side effects, and users receive medications at no cost. Trial design removes participants who leave the study early, potentially altering the research results.^1,2,4

Real World Results Tell a Different Story

Clinical studies do not reflect the broader population for whom GLP-1s are marketed.⁵ GLP-1 weight loss studies provide exaggerated results that are unrealistic for many users.

• Weight loss is modest and variable. One analysis of approximately 3,000 individuals in a real-world setting reported an average weight loss of 3.1% after 12 months of GLP-1 medication, far from the average 15% typically observed in clinical studies.⁶ Another study found that only a minority of users achieved weight loss of 5% or more after 12 and 24 months.⁷ 
• Individual variability affects results. Not everyone responds the same to GLP-1 medications. Some individuals are hyperresponders, while others are nonresponders. One analysis found that the top 10% of responders had lost up to 15% of their weight by 12 months compared to a 5% average weight gain among the bottom 10% of responders.⁶ A higher starting weight predicted larger losses, but the spread was substantial.
• Side effects are common. About 80% of users report nausea, reflux, bloating, diarrhea, or constipation, symptoms that worsen as doses escalate. Support and working with a dietitian can help manage symptoms, but most people don’t have access to these resources.⁴
• Lower doses, shorter durations. Many GLP-1 users start on or remain at lower doses to save money or help manage gastrointestinal side effects. Medication plans are not strictly followed. Unrealistic patient expectations for significant weight loss often lead to frustration and changes in medication.⁴ Some users take “drug holidays” for special occasions like vacations or social events, stalling weight loss.⁸ 
• High discontinuation rates. Users often discontinue the medication after one year due to side effects or the high cost. According to one study conducted in the United Kingdom, 45.2% of users discontinued GLP-1 medications after one year and 64.7% after 24 months.⁷
• Support is thin. Unlike in clinical trials, prescribers do not provide support for lifestyle interventions focusing on diet or exercise, and users are not required to attend counseling sessions. Providers do not typically provide users with specific guidelines on how to take their medications.⁶ Without these support systems, behavior change and weight loss lag.

The everyday environment does not facilitate easy success in overall health improvements. Weight loss is a nuanced process, and any progress toward improving your health should be celebrated.

Why This Matters for Public Policy

Many health plans and corporate wellness programs may view GLP-1s as a quick route to fewer obesity-related claims. However, if models predict outcomes of 15% or more weight loss, premiums and program budgets can quickly become misaligned with reality. 

Insurance covers only select nutrition services. Until public policy and insurance plans provide greater coverage for nutrition and mental health services (factors that influence weight), GLP-1 users will be left with misaligned weight loss expectations and frustration. GLP-1 medications are not a silver bullet. Rather, they are one piece of the puzzle necessary for weight loss.

What You Should Ask Before Starting GLP-1s

Choosing to start a GLP-1 is a big decision—weight loss is not guaranteed, you may need to remain on medication for life, and long-term effects are unknown.⁸ It is essential to consult with your healthcare provider to determine how GLP-1s may impact you.

1. What is my realistic weight loss range on this dose, given my health profile?
2. Could other weight-loss options or lower-cost options deliver similar benefits?
3. How might GLP-1s affect fertility, pregnancy, or breastfeeding plans?
4. What side effects am I most likely to experience, and how will we manage them?
5. What other strategies should I employ to support weight loss?
6. How long should I stay on the medication, and what happens if I stop?
7. What supports—such as a dietitian, trainer, or digital tracking tools—do I have access to?
8. How often will we reassess progress and adjust the plan?
9. How long will it take to see results or achieve my goal?
10. What happens if I don’t experience significant weight loss?

Before starting a GLP-1, ensure you have support systems and habits in place. Schedule an appointment with a registered dietitian, find an exercise routine you enjoy, and stock your pantry with foods that support your weight loss journey.

The Bottom Line

Clinical trials on GLP-1 medications lead to unrealistic weight loss expectations. GLP-1 medications can trigger significant weight loss, but only under meticulous conditions accessible to a few individuals outside of clinical trials. 

In the real world, it is possible to experience 3 to 5% weight loss, and that’s not failure. Any weight loss can be clinically meaningful, but it falls far short of the advertised 15-20% reduction.  

If you’re considering a GLP-1, pair the medication with a sustainable diet, regular exercise, and expert guidance. Whether you lose 3 or 15% of your body weight, the habits you build today support your health and metabolism long after you discontinue the medication.

Learn More With Signos’ Expert Advice

Data beats guesswork. A continuous glucose monitor (CGM) or biosensor enables you to enhance your health by tracking your diet, exercise, and glucose levels. With personalized insights into your metabolic health, you can take steps to begin improving your overall health and wellness.

Visit the Signos blog to learn strategies that support overall health and nutrition.