Who Are These GLP-1 Medications Actually For?

The clinical criteria, and why the answer matters more than the headlines

One of the most important conversations I think we can have as a training community is an honest one about who GLP-1 medications are actually designed for and who they are not. The cultural conversation around these drugs has drifted far enough from the clinical reality that I think it is causing real confusion for people on both sides of the debate. Let me try to bring it back to what the evidence actually says.

The Clinical Criteria

GLP-1 medications approved for weight management, specifically Wegovy (semaglutide 2.4 mg) and Zepbound (tirzepatide), carry clear FDA-approved eligibility criteria that reflect the populations studied in the clinical trials that generated the efficacy and safety data:

• A BMI of 30 or higher (classified as obesity), OR
• A BMI of 27 or higher (classified as overweight) alongside at least one weight-related health condition, such as type 2 diabetes, high blood pressure, high cholesterol, obstructive sleep apnea, or established cardiovascular disease.

These thresholds are not arbitrary. They reflect where the clinical trial data exists and where the benefit-to-risk profile has been evaluated. In December 2025, the World Health Organization added GLP-1 therapies to its Essential Medicines List, reflecting a growing global consensus that obesity warrants pharmacological treatment options alongside lifestyle intervention for appropriate patients.

BMI Is an Imperfect Tool

I want to be clear that BMI is a limited measure. It does not account for body fat distribution, the proportion of lean versus fat mass, or important metabolic markers like insulin resistance and blood pressure. Drs. Spencer and Karl Nadolsky discussed this at length in their October 2025 Docs Who Lift episode on the updated ACE Obesity Guidelines. The updated clinical guidance reflects a shift toward evaluating overall cardiometabolic health rather than relying on BMI alone. Two people with the same BMI can have meaningfully different metabolic risk profiles, which is why obesity medicine specialists evaluate the full clinical picture when making prescribing decisions.

Obesity as a Biological Condition

Something I have spent a lot of time thinking about in the context of coaching is how easy it is to conflate someone’s effort with their outcome. I have watched people train hard, work to eat intentionally, and still struggle enormously with their weight. The difficulty of implementing lifestyle interventions – alone – seems to be much higher for certain people. The research gives us a framework for understanding why.

Genetics, hormones, gut microbiome composition, sleep quality, stress, and the broader food environment all play documented roles in weight regulation. The STEP 1 trial extension (Wilding et al., Diabetes Obes Metab. 2022, PMID: 35441470) showed that approximately two-thirds of weight lost with semaglutide was regained within one year of stopping the medication, with cardiometabolic improvements also largely reverting.5 This pattern is consistent across GLP-1 discontinuation studies and reflects obesity as a chronic, biologically complex condition, not simply a problem of effort or motivation.

A note on the evidence: This does not mean lifestyle choices are irrelevant. The evidence consistently shows that structured nutrition and physical activity improve outcomes with and without medication. Biology and behavior interact, and both matter.

Who These Medications Are Not For

This matters as much as knowing who they are for. These medications are not appropriate for:

1. People at a healthy weight without qualifying clinical criteria. Using them for cosmetic weight loss in people who do not meet the medical threshold is not what the clinical evidence supports.
2. People with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN2). These are established prescribing contraindications.
3. People who are pregnant or planning to conceive in the near term. The Docs Who Lift episode GLP-1s and Fertility: What to Know Before Trying to Conceive (February 2026) with reproductive endocrinologist Dr. Lucky Sekhon addresses the nuance around preconception timing in detail.
4. People expecting medication alone to do the work. The clinical trials that generated these efficacy numbers were conducted alongside structured lifestyle intervention programs. The medication potentiates the results of those habits. It does not replace them.

The Docs Who Lift September 2025 episode Debunking the Myths of Metabolism and Weight Loss and their October 2025 ACE guidelines episode are worth a full listen if you want a thorough, evidence-grounded perspective on how the clinical thinking around obesity has shifted and why it matters.

Sources

1. Docs Who Lift: De-Emphasizing BMI, Prioritizing Health: What’s New in the ACE Obesity Guidelines. October 13, 2025. docswholift.com
2. Docs Who Lift: Debunking the Myths of Metabolism and Weight Loss. September 25, 2025. docswholift.com
3. Docs Who Lift: GLP-1s and Fertility: What to Know Before Trying to Conceive. February 12, 2026. docswholift.com
4. 3. Wilding JPH et al. STEP 1. N Engl J Med. 2021;384(11):989-1002. PMID: 33567185.
5. 4. Jastreboff AM et al. SURMOUNT-1. N Engl J Med. 2022;387(3):205-216. PMID: 35658024.
6. 5. Wilding JPH et al. Weight regain after withdrawal of semaglutide: STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564. PMID: 35441470.