# Do GLP-1 Drugs Improve Blood Vessel Function? The Same Number, Two Answers

Do GLP-1 drugs improve blood vessel function? An identical 0.11 estimate was significant against baseline and not against placebo, while hsCRP fell 37.8% in SELECT.

Publisher: This GLP Editorial Team
Canonical: https://thisglp.com/research/do-glp1-drugs-improve-blood-vessel-function
Updated: 2026-09-17
Published: 2026-09-16

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Evidence

# Do GLP-1 Drugs Improve Blood Vessel Function? The Same Number, Two Answers

Blood-vessel function rose 0.11 against baseline and 0.11 against placebo. The first was significant and the second was not. Only the comparison changed.

[This GLP Editorial Team](https://thisglp.com/about)September 20269 min readUpdated September 2026

Blood-vessel response, same estimate of 0.11 · vs baseline · p = 0.03 · vs placebo · p = 0.16 · no change · Only the comparison changed, not the measurement

**Research, not medical advice.** This GLP is independent and educational. Nothing here is a substitute for individualized care from a licensed clinician, and reading it creates no doctor–patient relationship. Talk to your own provider before starting, stopping, or changing any medication, peptide, or therapy. See our [methodology](https://thisglp.com/methodology) and [terms](https://thisglp.com/terms).

One measurement, two answers, and the comparison decides which one you get. In a 32-week trial of 120 people with type 2 diabetes, blood-vessel responsiveness rose 0.11 against each participant’s own baseline, 95% CI 0.008 to 0.21, p=0.03 [\[1\]](https://thisglp.com/research/do-glp1-drugs-improve-blood-vessel-function#ref-1). Against the placebo group the estimate was the same 0.11, with a 95% CI of −0.04 to 0.24 and p=0.16. Four adhesion molecules were measured and they did not move together, with one rising against placebo. The marker in this family that does move reliably is inflammation: hsCRP fell 37.8% at 104 weeks in SELECT [\[2\]](https://thisglp.com/research/do-glp1-drugs-improve-blood-vessel-function#ref-2).

## Key takeaways

-   A 32-week trial randomized 120 people with type 2 diabetes to semaglutide, empagliflozin, both, or placebo.
-   Blood-vessel responsiveness rose by 0.11 against each person's own baseline, 95% CI 0.008 to 0.21, p=0.03.
-   Against placebo the estimate was the same 0.11, 95% CI −0.04 to 0.24, p=0.16 — not significant.
-   One adhesion molecule fell against placebo and another rose, at 12.3 and 16.2 in the semaglutide and combination groups.
-   The authors attribute the placebo-comparison null to limited power, which is fair with about 30 people per arm.

Two sentences can describe one measurement. “Semaglutide improved blood vessel function, p=0.03.” And: “Semaglutide did not significantly improve blood vessel function versus placebo, p=0.16.” Both are accurate descriptions of the same number in the same study, and the difference between them is the entire subject of [choosing what to compare against](https://thisglp.com/research/do-glp1-drugs-cause-gout).

## The study

A post hoc analysis of a 32-week randomized trial that had been designed to look at cardio-renal organ damage. One hundred and twenty participants with type 2 diabetes, aged 50 or over, were randomized to semaglutide, empagliflozin, both together, or placebo. [\[1\]](https://thisglp.com/research/do-glp1-drugs-improve-blood-vessel-function#ref-1) The analysis looked at a measure of how well blood vessels widen in response to demand, and at four adhesion molecules the endothelium releases.

## The same estimate, twice

In the semaglutide group the vessel-response index rose 0.11 from each participant’s own starting value, with a 95% confidence interval of 0.008 to 0.21 and p=0.03. Compared with the placebo group it also rose 0.11 — with a confidence interval of −0.04 to 0.24 and p=0.16.

Nothing about the measurement changed. What changed is what it was held up against. People in a trial tend to improve for reasons that have nothing to do with the drug: closer monitoring, changed habits, regression to the mean, the season. A placebo group exists to absorb all of that, and when you subtract it the effect here stopped being distinguishable from noise.

Not shown is not shown absent

The authors say the placebo-comparison null likely reflects limited power, and they are probably right. One hundred and twenty people split four ways is about thirty per arm, which is very little for a biomarker with this much natural variation. So this page is not claiming the drug does nothing to the endothelium. It is claiming that the baseline comparison cannot tell you, and that the study which could have is too small.

## The markers disagreed with each other

Four adhesion molecules were measured and they did not move together. E-Selectin fell against placebo, by 9 in both the semaglutide group, 95% CI −14.1 to −5.1, and the combination group, 95% CI −14.3 to −5.2, both at p<0.01. That is the direction usually read as healthier.

VCAM-1 went the other way. It rose against placebo, by 12.3 in the semaglutide group, 95% CI 2.8 to 20.8, p=0.01, and by 16.2 in the combination group, 95% CI 7.2 to 24.3, p<0.01. P-Selectin and ICAM-1 did not move significantly in any group. The authors describe the responses as heterogeneous and suggest the molecules play distinct roles, which is an honest way of saying nobody knows what the pattern means.

Note what a selective summary could do with that. Quote E-Selectin, omit VCAM-1, and this becomes a study showing improved endothelial health. It is the same move [a composite endpoint makes structurally](https://thisglp.com/research/tirzepatide-heart-failure-composite), performed by hand.

## The marker that does move, and one that moved too much

Inflammation is the comparison worth having beside this one. A prespecified SELECT substudy reported high-sensitivity CRP down 37.8% at 104 weeks against placebo [\[2\]](https://thisglp.com/research/do-glp1-drugs-improve-blood-vessel-function#ref-2). The reduction was evident by weeks 4 and 8, and it appeared among participants who did not lose weight. That is a placebo comparison in a trial of 17,604 people, and its authors still describe reduced inflammation as contributing “in part” rather than as the mechanism. The reading is in [the hsCRP substudy](https://thisglp.com/research/do-glp1-drugs-reduce-inflammation).

A third study shows what happens when the comparison is right and the result is still too large. A matched cohort of 4,153 patients per arm compared these drugs against mineralocorticoid receptor antagonists as fourth-line therapy in resistant hypertension [\[3\]](https://thisglp.com/research/do-glp1-drugs-improve-blood-vessel-function#ref-3). Blood pressure fell by a similar amount in both arms, −5.7 mmHg against −6.3 mmHg at 12 weeks, while all-cause mortality came in at a hazard ratio of 0.34. A two-thirds reduction in death with the treated quantity equalized is a confounding signature, set out in [same blood pressure, different outcomes](https://thisglp.com/research/do-glp1-drugs-help-resistant-hypertension).

## Why any of this matters to a reader

Not because endothelial biomarkers should influence a purchase. They should not — these are laboratory measures in 120 people, not events in anybody.

It matters because “improved from baseline” is everywhere. It appears in clinic testimonials, in single-arm studies, in before-and-after marketing, and in summaries of real trials that had a placebo group available and quoted the baseline comparison anyway. Once you notice the phrase you cannot stop seeing it, and it is the same weakness that makes [an uncontrolled study](https://thisglp.com/research/do-glp1-drugs-help-hidradenitis-suppurativa) unable to show what it appears to show.

The test is one question: compared to what? If the answer is “to how they were before,” you have been told how a group of people changed over time, not what the drug did. Almost nothing a seller publishes survives that question, which [the disclosure scorecard](https://thisglp.com/tools/what-sellers-publish) measures from the other direction.

## Frequently asked

Do GLP-1 drugs improve blood vessel function?

This trial cannot say. The same 0.11 estimate was significant against each person's own baseline and not significant against placebo, and the authors attribute that to limited power at about thirty people per arm.

How can the same number be significant and not significant?

Because significance depends on the comparison. Against each person's own baseline the interval was 0.008 to 0.21, which excludes zero. Against the placebo group it was −0.04 to 0.24, which does not.

Does semaglutide improve blood vessel function?

This study cannot say. The placebo comparison was not significant and the authors attribute that to limited power, with about thirty people per arm.

Why did one marker get worse?

VCAM-1 rose against placebo while E-Selectin fell. The authors call the responses heterogeneous and suggest the molecules have distinct roles. Nobody knows what the pattern means.

Should this change what I buy?

No. These are laboratory markers in 120 people, not clinical events. The transferable part is the question to ask of any result: compared to what?

## Sources

1.  \[1\] Gullaksen S, et al. (2026). Effects of semaglutide and empagliflozin on markers of endothelial function in persons with type 2 diabetes: A post hoc analysis of a randomized clinical trial Journal of Diabetes and Its Complications. [PMID 42679726](https://pubmed.ncbi.nlm.nih.gov/42679726/)
2.  \[2\] Plutzky J, Bogdański P, Colhoun HM, Dağdelen S, et al. (2026). Effect of Semaglutide on the Inflammatory Biomarker High-Sensitivity CRP in Patients With Established Cardiovascular Disease and Overweight or Obesity in SELECT: A Prespecified Secondary Analysis Circulation. [PMID 42610271](https://pubmed.ncbi.nlm.nih.gov/42610271/)
3.  \[3\] Tian Z, et al. (2026). Comparative effectiveness of GLP-1 receptor agonists versus mineralocorticoid receptor antagonists as fourth-line pharmacological therapy in patients with resistant hypertension and overweight or obesity: a retrospective multicenter cohort study in the USA eClinicalMedicine. [PMID 42701458](https://pubmed.ncbi.nlm.nih.gov/42701458/)

## Where to get it

### Best GLP-1 injections

Every injectable seller we can verify, with the price each one publishes and an honest read of what the trials measured.

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