The marketing around GLP-1 medications is full of impressive-sounding numbers. "Up to 22% body weight loss." "Clinically proven results." "The most effective treatment ever." Some of these claims are accurate - in specific contexts, at specific doses, under specific conditions. Understanding what the actual trial data says - and what it doesn't - helps you evaluate your own treatment honestly and have more productive conversations with your prescriber.

The STEP trials: what semaglutide actually produced

Semaglutide (the active ingredient in Ozempic and Wegovy) was studied in the STEP (Semaglutide Treatment Effect in People with obesity) trial programme. These were large, well-designed, randomised controlled trials with results that hold up to scrutiny.

STEP 1 is the most widely cited. Published in 2021, it enrolled 1,961 adults with a BMI of 30 or greater (or 27 with at least one weight-related condition) without type 2 diabetes. Participants received semaglutide 2.4mg weekly or placebo alongside lifestyle intervention over 68 weeks. The results:

  • Mean body weight reduction: 14.9% in the semaglutide group vs 2.4% in the placebo group
  • 86.4% of semaglutide participants achieved at least 5% weight loss
  • 69.1% achieved at least 10% weight loss
  • 50.5% achieved at least 15% weight loss

Those are meaningful numbers. Half of trial participants lost at least 15% of their starting body weight. But notice the spread - 14.9% is the mean, not the ceiling. Some people lost considerably more, others considerably less.

STEP 4 provides important data on what happens when you stop. After 20 weeks on semaglutide, participants were randomised to continue or switch to placebo for another 48 weeks. The continuation group lost an additional 7.9 percentage points of body weight. The placebo group regained 6.9 percentage points. By the end, the two groups were 14.8 percentage points apart in total weight change. The lesson is straightforward: stopping the medication reverses most of the benefit over time.

SELECT (2023) extended semaglutide's evidence base beyond weight. This trial enrolled 17,604 adults with existing cardiovascular disease but without diabetes and ran for a mean of 39.8 months. Semaglutide reduced major adverse cardiovascular events (heart attack, stroke, cardiovascular death) by 20% versus placebo. That's the trial that moved semaglutide from a weight loss drug to a cardiovascular treatment in clinical guidelines.

The SURMOUNT trials: what tirzepatide produced

Tirzepatide (Mounjaro for diabetes, Zepbound for weight loss) targets both GLP-1 and GIP receptors - a dual mechanism that produces more potent metabolic effects than GLP-1 alone. The SURMOUNT trial programme confirmed this with numbers that exceeded semaglutide's at every comparable time point.

SURMOUNT-1 (2022) enrolled 2,539 adults without diabetes and ran for 72 weeks. Results by dose:

  • Tirzepatide 5mg: mean weight reduction 15.0%
  • Tirzepatide 10mg: mean weight reduction 19.5%
  • Tirzepatide 15mg: mean weight reduction 20.9%
  • Placebo: mean weight reduction 3.1%

The 15mg dose produced roughly 20% average weight loss. At 40 weeks, 57% of participants on the 15mg dose had lost 20% or more of their body weight.

SURMOUNT-5 is the one that directly answered the question everyone was asking: tirzepatide vs semaglutide head to head. Published in 2025, it randomised participants to tirzepatide 10mg or 15mg versus semaglutide 2.4mg over 72 weeks. Tirzepatide produced approximately 20.2% average weight loss; semaglutide produced approximately 13.7%. That 6.5 percentage point gap is statistically and clinically significant - not a rounding error.

Three questions to ask about any GLP-1 result you read

A lot of marketing copy in the GLP-1 space applies trial statistics to situations they weren't measured in. Before you take any weight loss percentage seriously, ask:

  1. What medication was studied? Compounded semaglutide is not the same as FDA-approved Wegovy. No compounded GLP-1 medications have been evaluated in randomised controlled trials comparable to STEP or SURMOUNT. Applying Wegovy's 14.9% average to a compounded formulation is not supported by evidence.
  2. At what dose? The impressive trial results come from maximum approved doses reached after months of careful titration. A programme that starts and stays at a lower dose will produce lower results. Phrases like "up to 22% weight loss" describe outlier outcomes at top doses, not the average experience.
  3. Under what conditions? Trial participants receive intensive support - weekly check-ins, dietary guidance, behavioural counselling, and close monitoring. Real-world telehealth programmes typically produce 8–12% average weight loss over 12 months, substantially below trial averages. This is expected and documented, not a sign that something went wrong.

What the real-world data shows

A 2025 study specifically examining real-world telehealth GLP-1 programmes - the kind of prescription service many people use today - found average weight loss of approximately 8–12% over 12 months. That's still clinically meaningful. Losing 8% of body weight reduces blood pressure, improves insulin sensitivity, lowers cardiovascular risk, and reduces strain on joints. It's a good outcome. It's just not the 20.9% you see in the headlines.

The gap exists for several well-understood reasons: more missed doses, slower dose escalation due to tolerability, less structured dietary support, higher dropout rates before reaching maximum dose, and patient populations with more comorbidities than trial participants. None of this is a failure of the treatment or the patient. It's the expected translation from tightly controlled research to everyday care.

Safety signals you should know about

The clinical evidence for GLP-1 medications is strong - but it's not without safety considerations worth understanding.

Both semaglutide and tirzepatide carry a contraindication for patients with a personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2). This is based on animal data showing thyroid C-cell tumours at high doses; human risk is not confirmed but the contraindication stands.

Gallbladder disease is a documented risk. Both drugs increase the risk of cholelithiasis (gallstones) and cholecystitis. The STEP 1 trial showed gallbladder-related adverse events in 2.6% of semaglutide participants versus 1.2% in the placebo group.

Lean mass loss is frequently cited as a concern. Initial data from several trials showed that roughly 25–40% of weight lost on GLP-1 medications came from lean mass rather than fat. More recent research, including Cell Reports Medicine data from 2026, suggests the proportion of muscle loss may be lower than initially reported - particularly when protein intake is adequate. This remains an active area of research.

Gastrointestinal side effects - nausea, vomiting, diarrhoea, constipation - are the most common, affecting roughly 30–44% of trial participants at some point. Most resolve after dose adjustment, but they drive a significant portion of discontinuations.

The compounding question

One area where the clinical trial data is especially important to understand is compounded GLP-1 medications. During the semaglutide and tirzepatide shortage period, compounding pharmacies filled the supply gap with versions of these drugs that were not subject to FDA's bioequivalence, sterility, or manufacturing quality standards that apply to branded Wegovy and Zepbound.

The FDA resolved the semaglutide shortage in early 2025 and proposed permanent exclusion of semaglutide, tirzepatide, and liraglutide from the 503B compounding bulks list. The public comment period closes June 29, 2026. If the exclusion proceeds, compounded versions will no longer be legally available.

The clinical evidence that supports GLP-1 medications comes from branded formulations at studied doses. There are no published randomised controlled trials on compounded versions. Marketing that applies STEP or SURMOUNT statistics to compounded formulations is not supported by the evidence base.

Nutrition: the variable the trials mostly ignored

Here's what the STEP and SURMOUNT trials didn't measure well: what happened to participants' micronutrient status over the course of treatment. Trial protocols focused on weight outcomes, cardiovascular endpoints, and safety signals. Systematic measurement of vitamin B12, vitamin D, iron, and magnesium levels was not a primary endpoint in the major trials.

That gap has since been partly filled by post-market research. A 2026 meta-analysis of 480,825 adults found GLP-1 users showed 13.6% rates of vitamin D deficiency and 64% rates of insufficient iron intake. A separate Harvard Health analysis flagged six nutrients of particular concern: vitamin B12, vitamin D, calcium, iron, fibre, and protein.

If you're on semaglutide or tirzepatide and eating substantially less than before - which is the whole point of the treatment - you're absorbing substantially fewer micronutrients. This is not a side effect the trial protocols were designed to catch. It's a practical consequence of effective appetite suppression that needs active management.

GLP-1 Shield supplements are formulated specifically to address the nutrient deficiencies most commonly documented in GLP-1 medication users, based on the post-market research that the original trial programmes didn't cover.

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Frequently asked questions

Is tirzepatide better than semaglutide for weight loss?
Based on the SURMOUNT-5 head-to-head trial, yes - tirzepatide produced approximately 20.2% average weight loss versus 13.7% for semaglutide 2.4mg over 72 weeks. This 6.5 percentage point gap is statistically and clinically significant. Tirzepatide's dual GIP/GLP-1 mechanism appears to produce more potent metabolic effects than GLP-1 targeting alone. Individual responses still vary considerably.
Why are my results lower than what the clinical trials showed?
Real-world telehealth programmes typically produce 8–12% average weight loss versus 14–21% in clinical trials. Trial participants receive intensive monitoring, dietary support, and behavioural counselling that most real-world programmes don't replicate. Slower dose escalation, more missed doses, and higher dropout rates before reaching maximum dose all contribute to the gap. This is expected and doesn't mean your treatment isn't working.
Is compounded semaglutide as effective as Wegovy?
There are no published randomised controlled trials on compounded semaglutide comparable to the STEP trials. Applying Wegovy's 14.9% average weight loss figure to compounded formulations is not supported by evidence. Compounded versions also lack the bioequivalence testing and manufacturing quality controls required of FDA-approved branded formulations.
What nutrients am I most likely to be deficient in on GLP-1 medications?
A 2026 meta-analysis identified vitamin D deficiency in 13.6% of GLP-1 users and insufficient iron intake in 64%. Vitamin B12, calcium, magnesium, and protein are also commonly flagged. These deficiencies result from reduced total food intake - eating less means absorbing less of everything, including essential micronutrients. Active monitoring and targeted supplementation are recommended for long-term GLP-1 users.