Lab Literacy / How Trials Decided Who Gets What Peptide
9 min readA number appears in a trial protocol: HbA1c must be 7% or above. Another: waist circumference at least 95 centimeters. Another: eGFR no lower than 30.
These are not suggestions. They are hard gates — a participant either meets them or they do not get into the study. And the gates are not interchangeable. The number that admits you to a semaglutide diabetes trial is the same number that excludes you from a tirzepatide obesity trial.
Understanding these thresholds is what separates reading a trial abstract from actually understanding who the trial was done in. The results only apply to the population that passed through these gates. If the enrollment criteria do not describe you, the results do not describe you either — no matter how impressive the headline number is.
Here are the real enrollment criteria from the major published programs, side by side.
Tesamorelin was studied in a very specific population: people living with HIV who had developed abnormal fat redistribution from both the virus and antiretroviral therapy. The enrollment criteria reflect that focus.
| Criterion | Threshold | Why it existed |
|---|---|---|
| HIV status | Positive, on stable ART | The indication was HIV-associated lipodystrophy — the drug was not tested in anyone else |
| Waist circumference | ≥95 cm (men) / ≥94 cm (women) | Defined the abnormal fat distribution the drug was meant to address |
| Waist-to-hip ratio | Elevated | Reinforced the visceral-fat pattern |
| CD4 count | >100 cells/μL | Confirmed immune stability |
| Viral load | <10,000 copies/mL | Confirmed virologic control |
| Prior GH/GRF use | None in prior 6 months | Prevented confounding from recent GH-axis exposure |
| Diabetes | Excluded if insulin-treated | GH affects glucose; insulin-treated T2D was a safety exclusion |
| Malignancy | Active cancer excluded | GH can promote cell proliferation |
| Blood pressure | Untreated hypertension excluded | Safety gate |
The primary endpoint was not a blood test at all — it was a CT scan at the L4-L5 vertebral level, measuring the percentage change in visceral adipose tissue at 26 weeks. That is the only peptide with an FDA approval built on an imaging endpoint. The enrollment criteria existed to make sure the people receiving it actually had the condition the imaging was measuring.
The SURMOUNT program studied tirzepatide in people with obesity who did not have diabetes. That distinction drove nearly every lab gate.
| Criterion | Threshold | Why it existed |
|---|---|---|
| BMI | ≥30, or ≥27 with a weight-related comorbidity | Defined the study population |
| HbA1c | <6.5% (non-diabetic arm) | This is the line that separated SURMOUNT from SUSTAIN. Above 6.5% meant undiagnosed diabetes, and you were out |
| eGFR | ≥30 mL/min/1.73m² | Below 30 meant significant kidney impairment — excluded for safety |
| ALT | ≤3× upper limit of normal | Liver function gate; above this suggests active liver disease |
| Bilirubin | ≤1.2× upper limit of normal | Additional liver function check |
| TSH | 0.4-6.0 mIU/L | Thyroid function had to be within this window |
| Calcitonin | <20 ng/L (if eGFR ≥60); <35 ng/L (if eGFR <60) | Medullary thyroid carcinoma surveillance — class-specific GLP-1 concern |
| Blood pressure | <160/100 mmHg | Safety gate for cardiovascular risk |
The calcitonin threshold is worth pausing on because it is the most specific gate in any of these trials. Calcitonin is a tumor marker for medullary thyroid carcinoma, a rare cancer type. GLP-1 receptor agonists carry a labeled warning about this cancer in animal studies, so trial designers measured calcitonin at baseline and excluded anyone whose level was too high. The threshold even adjusts for kidney function, because impaired kidneys naturally raise calcitonin levels. It is a precise, class-specific safety gate — you will not find it in GH-axis trials because the concern does not apply there.
The SUSTAIN program is the mirror image of SURMOUNT on the HbA1c axis. Where SURMOUNT excluded diabetes, SUSTAIN required it.
| Criterion | Threshold | Why it existed |
|---|---|---|
| Diagnosis | Type 2 diabetes | The entire trial population had T2D |
| HbA1c | 7-10% | You had to have established but not severe diabetes — below 7% was not diabetic enough, above 10% was too advanced |
| Titration | 0.25 → 0.5 → 1.0 mg, every 4 weeks | Fixed escalation schedule based on tolerance, not lab results |
The SUSTAIN enrollment is the simplest of the group because the defining gate is a single number: HbA1c at or above 7%. That number is the line between "this person has type 2 diabetes" and "this person does not." SURMOUNT drew the line at 6.5% to keep undiagnosed diabetics out. SUSTAIN drew it at 7% to keep only confirmed diabetics in. Same test, opposite sides of the same fence.
Growth hormone replacement is not a single trial — it is a treatment framework established by clinical guidelines, and its enrollment process is the most lab-intensive of any peptide-related protocol.
| Criterion | Threshold | Why it existed |
|---|---|---|
| GH stimulation test | Failed ITT or GHRH+arginine test | Diagnosis of adult growth hormone deficiency requires a failed stimulation test — no other marker substitutes |
| Starting dose | 0.2-0.4 mg/day | Low starting point; titrated upward based on response |
| Titration interval | Every 4-8 weeks | IGF-1 is checked each cycle; dose adjusts based on the result |
| IGF-1 target | Upper-normal for age and sex | The goal is to reach the top of the normal range — never above it |
| Monitoring | Glucose, HbA1c, thyroid, prolactin | GH affects all of these; tracked alongside IGF-1 |
The stimulation test requirement is what sets GH replacement apart from every other protocol on this list. You cannot enroll based on a symptom, a body measurement, or a single IGF-1 level. You must demonstrate that your pituitary cannot produce adequate growth hormone when challenged — either through an insulin tolerance test (ITT), which is considered the gold standard, or a GHRH-plus-arginine stimulation test. A low baseline IGF-1 raises suspicion, but it does not make the diagnosis on its own. The test does.
MK-677 occupies a different position in the evidence base: it is an oral GH secretagogue studied in elderly adults, not an injectable approved drug.
| Criterion | Details from the trial |
|---|---|
| Population | Elderly adults (65+ years) |
| Mean baseline IGF-1 | 141 mcg/L (low for age — the pattern the intervention targeted) |
| Dose | 25 mg/day, oral |
| IGF-1 at study end | 219 mcg/L |
| Body composition | DEXA-measured fat-free mass |
| Glucose effect | Fasting glucose modestly increased; no participant developed diabetes over two years |
This trial is notable for what it demonstrated about monitoring. Fasting glucose went up slightly — which is expected with any GH-axis intervention — but over two full years, not a single participant crossed into diabetes. That is a meaningful safety signal, and it only exists because the trial measured glucose at baseline and tracked it throughout.
When you lay these criteria next to each other, the logic becomes visible.
Each trial's gates are specific to what the intervention does and who it is meant for. Tesamorelin's gates are built around HIV-associated lipodystrophy — if you do not have that condition, the waist-circumference and CD4 criteria are irrelevant. SURMOUNT's calcitonin gate exists because of a GLP-1-specific cancer concern — it has no place in a GH-axis protocol. SUSTAIN's HbA1c floor is there because the trial was about diabetes — applying that same floor to a non-diabetic person would exclude the entire target population.
This is why importing a lab cutoff from one trial into a different context is not straightforward. The number means something only within the population and the protocol it was designed for.
Every trial result is conditional on who was allowed in. When you read that tesamorelin reduced visceral fat by 15%, that number applies to HIV-positive adults on stable antiretroviral therapy with waist circumference above 95 cm. It does not apply to someone with metabolic obesity and no HIV diagnosis, because that person would never have passed enrollment.
The enrollment criteria are not background noise in a trial protocol. They are the part that determines whether the results that follow have any relevance to a given situation. Skipping them is like reading a study's conclusions without reading its methods — you get the headline, but you lose the context that makes the headline meaningful.
This article is for educational purposes and is not medical advice. It describes published clinical trial eligibility criteria. It does not recommend any peptide, test, or protocol. Decisions about treatment belong with a qualified clinician who knows your medical history.
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