Peptide basics

Men in GLP-1 weight-loss trials: what the smaller subgroups showed

This page contains no dose, schedule or route, and makes no claim that any compound works or is appropriate for anyone. It reports what the published male subgroups contained and what has been analysed from them.

How many men were actually there

STEP 1's posted baseline table records 508 male participants out of 1,961 randomised. In the semaglutide arm specifically, 351 of 1,306 participants were male.¹

A 2023 review of the semaglutide phase-3a programme put the same numbers as proportions of each trial's semaglutide population: 26.9% men in STEP 1, 22.6% in STEP 3 and 19.8% in STEP 4. Its summary described men as understudied in that programme.²

SURMOUNT-1 had the largest male share of the big obesity trials, at 825 men out of 2,539 — 32.5%. Still a minority, but a third rather than a fifth.⁷

What the male subgroups reported

The most-quoted sex-split figure from this literature is the STEP 1 comparison. The 2023 review reports an estimated treatment difference in weight reduction against placebo of −14.0% in women and −8.0% in men. Both figures come from subgroup analysis, not from a comparison the trial was designed to make.²

A 2025 systematic review and meta-analysis pooled 14 randomised trials that reported weight change by sex, across dulaglutide, exenatide, liraglutide, semaglutide and retatrutide. Females lost more weight than males, with a pooled mean difference of 1.04 kg and 1.69 percentage points.³

The same analysis found the sex gap widened as the overall size of the weight reduction grew, and that trials with a weight-reduction indication showed a larger gap than trials with other indications. Its authors noted that many included studies lacked granular sex-stratified data.³

• Pooled difference in absolute weight change, females minus males: 1.04 kg (95% CI 0.70 to 1.38).
• Pooled difference in percentage weight change: 1.69% (95% CI 0.78 to 2.61).
• The gap was larger where total weight reduction was larger.
• Background treatment, treatment duration, baseline weight and type of control showed no subgroup differences in the sex effect.³

Why these numbers cannot carry much weight

Subgroup analyses are the weakest routinely published part of a trial report. The standard critique, set out in a widely used NEJM methods paper, is that they multiply the number of comparisons, are frequently not pre-specified, and are rarely powered to detect an interaction even when one exists.⁶

That paper's practical test is whether the trial reported a formal test of interaction between the subgroup variable and treatment, rather than two separate within-group estimates. Two separate estimates that look different are not evidence that the effect differs.⁶

Apply that test here and the male numbers get thinner. A −14.0% versus −8.0% comparison is two within-group estimates. Without a pre-specified interaction test sized for it, the honest reading is that the trial observed this and did not establish it.²⁶

The trial where men were half the room

STEP 2, which studied people with type 2 diabetes rather than obesity alone, is the exception in the programme. It randomised 1,210 participants: 616 female and 594 male, with a mean age of 55.⁴

That is the strongest available evidence that these ratios follow the condition and the eligibility criteria rather than the compound. Change the indication and the roster changes with it.¹⁴

SELECT goes further in the same direction. Its cardiovascular population was 12,732 men and 4,872 women — 72.3% male — with a mean age of 61.6 years.⁵

For semaglutide, the male evidence is spread unevenly: thin in the obesity trials, near-balanced in the type 2 diabetes trial, and dominant in the cardiovascular outcomes trial. Which of those a claim comes from changes what it describes.

What is still missing for men

The 2023 review identified a second gap beyond sample size: it noted that the effect of GLP-1-induced weight loss on male sexual function and fertility remains substantially understudied, with very little published work on the gonadal axis in men.²

And the meta-analysis noted the practical obstacle to closing any of this: many trials simply do not publish results split by sex, so pooling has to work with whatever fragments have been reported.³

Common questions