Women and peptide research gaps: the missing data

Key takeaways

• Until the 1990s, women were systematically underrepresented in US phase 1 pharmacokinetic studies. The 1993 NIH Revitalization Act required NIH-funded research to include women and analyze results by sex .
• Modern GLP-1 obesity trials enroll female-majority cohorts: STEP-1 was 74 percent female and SURMOUNT-1 was 67.5 percent . Both report results by sex.
• The cardiovascular-outcomes GLP-1 trials enroll fewer women because the qualifying-CVD populations skew male: SUSTAIN-6 was 39 percent female and SELECT was 28 percent .
• Older research peptides (BPC-157, TB-500, ipamorelin, CJC-1295) have little published human PK at all, and none of it is sex-stratified. The SARM LGD-4033 was characterized in 76 healthy men ; female-specific data are essentially absent.
• GLP-1 drugs are not recommended in pregnancy. Semaglutide labels say discontinue at least 2 months before a planned pregnancy because of the long washout ; lactation data are limited.

Why the old data leans male

Until the 1990s, women were systematically underrepresented in many US phase 1 pharmacokinetic and pharmacodynamic studies. The reasons given at the time were fear of teratogenic exposure (post-thalidomide caution), hormonal-cycle variability, and keeping small studies statistically simple. The result is that early dose-finding for a lot of older drug classes was anchored on male physiology.

The 1993 NIH Revitalization Act required NIH-funded clinical research to include women and to analyze results by sex, and enrollment did climb: women have made up more than half of NIH-supported clinical research participants every year since 2018 . Reporting caught up more slowly. An audit of NIH-funded randomized trials published in 2015 found only about a quarter (26 percent) reported any outcome by sex, no better than a decade earlier . Inclusion is close to solved. Sex-disaggregated analysis still lags.

How sex shifts pharmacokinetics

• Body size shifts volume of distribution. Per-kilogram dosing helps but does not fully resolve clearance differences for some compounds.
• Body composition (typically higher percent body fat in women) shifts volume of distribution for lipophilic drugs.
• Some hepatic CYP enzymes differ by sex; CYP3A4 activity runs higher in women, which can shift clearance of substrate drugs.
• Renal clearance differs (lower GFR per body weight in women), shifting the half-life of renally cleared drugs.
• Population PK on the modern GLP-1 trials includes sex as a covariate. For semaglutide, sex had no clinically meaningful effect on exposure; body weight did .
• Older non-peptide research compounds (some SARMs, older nootropics) have human PK drawn from much smaller and more male-skewed samples, which is worth knowing when you read a dose recommendation.

GLP-1 trials enroll and analyze women

Modern obesity and diabetes trials of GLP-1 and dual agonists enrolled female-majority or near-balanced cohorts and reported results by sex. The pattern:

• STEP-1 (semaglutide 2.4 mg): 74 percent female . Women lost more relative weight than men. The estimated treatment difference versus placebo was about -14 percent in women versus -8 percent in men, per a 2023 peer-reviewed review summarizing the STEP subgroup data .
• SURMOUNT-1 (tirzepatide 5/10/15 mg): 67.5 percent female . The trial enrolled and analyzed a female-majority cohort across all three doses.
• SUSTAIN-6 (semaglutide, cardiovascular outcomes in type 2 diabetes): 39 percent female. The cardiovascular benefit held across sexes (p = 0.45 for the interaction), though the female subgroup was the smaller of the two .
• SELECT (semaglutide 2.4 mg in established CVD without diabetes): 28 percent female, lower because the qualifying CVD population skews male .

GLP-1 efficacy and safety data in women now rest on tens of thousands of female trial participants, including in the long-term outcome trials. For this drug class the historical gap is largely closed.

Where it has closed, and where it has not

The gap closes fastest where there is an active phase 3 program (GLP-1, oncology, autoimmune). It stays open here:

• Older research peptides (BPC-157, TB-500, ipamorelin, CJC-1295): little published human PK at all, and what exists comes from small healthy-male cohorts. Female-specific data are essentially absent.
• SARMs: the LGD-4033 phase 1 work was 76 healthy men , and RAD-140's human data are similarly thin. Sex-specific dosing data barely exist.
• Cardiovascular-outcomes trials, where low female enrollment tracks the qualifying disease (established CVD, HFpEF) rather than any exclusion.
• Pregnancy and lactation, where postmarketing surveillance is the main lens and accumulates slowly. The FDA pregnancy and lactation labeling rule sets how that data appears on product labels .

Menopausal status is a sub-gap of its own

Perimenopause and menopause bring metabolic changes (visceral fat gain, shifts in insulin sensitivity and lipids) that overlap with the reasons people take GLP-1 and peptide therapy. Estrogen status is another moving part in how women respond.

Trials almost never break their results out by menopausal status. Most report by sex and stop there, so premenopausal, perimenopausal, and postmenopausal responses sit inside one women number. That is a real sub-gap inside the larger one.

Pregnancy and lactation: thin data, clear labels

GLP-1 drugs and most research peptides are not recommended in pregnancy. Animal reproduction studies flagged harm for both semaglutide and tirzepatide. Semaglutide labels say discontinue at least 2 months before a planned pregnancy because the drug clears slowly . Tirzepatide labels do not set a pre-pregnancy window; they say stop it once a pregnancy is recognized, and they warn that tirzepatide can lower the effectiveness of oral contraceptives, so switch to or add a non-oral method for 4 weeks after starting and after each dose increase .

Lactation data are thin across the board; most labels advise weighing benefit against risk. The FDA pregnancy and lactation labeling rule replaced the old A, B, C, D, X letter categories with narrative risk summaries, so current labels describe the data rather than grading it with a letter .

What would actually close it

The fix is not exotic: run sex-stratified analysis on every adequately powered trial, and do dedicated PK/PD work in female cohorts where it was skipped. Pregnancy registries for GLP-1 drugs and peptides, like the teratogen registries that already exist for other drug classes, would close a gap that postmarketing reports fill only slowly. For active trials by drug class and population, ClinicalTrials.gov is the place to look .

The honest read

Modern GLP-1 trials have largely closed the sex-representation gap for that drug class. Older research peptides, SARMs, and anything whose original PK predates the 1990s still lean on male-skewed samples. Pregnancy and lactation data are limited across the board, and menopausal status is a sub-question current trials mostly ignore.

For research and educational purposes only. Not medical advice.

pepSmart has not commissioned independent clinical review of this article.

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Sources: 12 entries, primary canon (FDA drug labels, NIH policy, peer-reviewed trials and subgroup analyses, ClinicalTrials.gov) plus one peer-reviewed review acknowledged inline, last reviewed 2026-07-08.

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