SURMOUNT-1: glycemia markers and T2D risk

A post hoc analysis of the three-year SURMOUNT-1 trial, published in the Journal of the Endocrine Society in August 2026, asked a practical question: among adults with obesity and prediabetes who did not take tirzepatide, which blood test best identified those who went on to develop type 2 diabetes (T2D)?^[1] The answer has implications for screening and for deciding who most needs aggressive pharmacologic intervention.

The study, led by Rodolfo J. Galindo and colleagues, evaluated three glycemia-based criteria in the placebo group (n=270): an oral glucose tolerance test (OGTT) one-hour glucose at or above 155 mg/dL, a fasting serum glucose (FSG) at or above 110 mg/dL, and a haemoglobin A1c (HbA1c) at or above 6%. Each criterion was tested for how well it classified participants who actually progressed to T2D over the 176-week follow-up^[1].

How the three markers compared

OGTT one-hour glucose was the most sensitive: it correctly flagged 83% of participants who later developed T2D (sensitivity 0.83), though with low specificity (0.25), meaning it generated many false positives. FSG and HbA1c reversed that trade-off: FSG had 87% specificity but only 50% sensitivity; HbA1c had 69% specificity and 47% sensitivity^[1].

Critically, HbA1c alone missed 53% of participants who progressed to T2D. That is a large share to leave unidentified, particularly in a population already classified as prediabetic. The FSG and OGTT criteria were better aligned: every participant who met the FSG high-risk threshold also met the OGTT one-hour glucose threshold, and 82% of those who met the HbA1c threshold also met the OGTT threshold.

Among the placebo participants, 67% of those who progressed to T2D met at least two of the three high-risk criteria at baseline, suggesting that concordance across markers is itself a useful signal of near-term risk.

What tirzepatide did across risk groups

The main SURMOUNT-1 trial had already reported that tirzepatide reduced incident T2D in participants with prediabetes, with the 10 mg and 15 mg arms achieving a 94% relative risk reduction compared with placebo^[2]. This post hoc analysis stratified that reduction by baseline glycemia risk.

For participants classified as high-risk by the OGTT one-hour glucose criterion (baseline glucose at or above 155 mg/dL), tirzepatide reduced new-onset T2D by 90% to 99% relative to placebo. In the standard-risk group under the same criterion, the reduction was 68% to 91%. A similar gradient appeared for the FSG criterion: among those meeting the FSG high-risk threshold, the high-risk group saw 99% relative risk reduction (zero events in 119 tirzepatide participants versus 18 events in 49 placebo participants). The interaction p-value for this FSG result was 0.031, suggesting the differential by risk group was not due to chance^[1].

One important context note: across all the tirzepatide arms, T2D event numbers were small (often around five cases). Small event counts limit the statistical power of subgroup comparisons, and the authors acknowledge this limitation directly.

Why the OGTT one-hour criterion matters

The OGTT one-hour glucose threshold used here (155 mg/dL) aligns with a 2023 International Diabetes Federation consensus recommendation for using OGTT one-hour glucose in prediabetes screening. Standard clinical classification in most guidelines relies on fasting glucose or HbA1c; the OGTT one-hour reading is harder to obtain (it requires patients to drink a glucose load and wait an hour) but appears to capture a pool of high-risk individuals that simpler tests miss^[1].

The finding that 53% of T2D progressors would have been missed by HbA1c alone is the most actionable number in the paper. If confirmed in other datasets, it suggests clinicians relying only on HbA1c to risk-stratify prediabetes could be systematically underestimating which patients most need treatment.

What this analysis cannot tell us

This is a post hoc, exploratory analysis, not a pre-specified outcome. The glycemia criteria were tested retrospectively in participants who happened to be in the placebo group, which limits causal inference. The positive predictive values across all three criteria were low (0.15 to 0.37), reflecting that most participants meeting any high-risk threshold did not progress to T2D within the trial period, whether on placebo or not.

SURMOUNT-1 enrolled adults with obesity or overweight without diabetes at baseline, so results may not generalise to populations with a different cardiometabolic profile. The 176-week window also does not tell us whether a participant who remained non-diabetic over three years would stay that way over longer periods.

What we do not yet know

Whether the OGTT one-hour glucose threshold at 155 mg/dL performs as well in populations beyond the SURMOUNT-1 cohort, which was majority-White, majority-US, and enrolled specifically for an obesity weight-loss trial. Whether the benefit gradient (greater absolute reduction in the highest-risk group) holds in longer follow-up or at different doses. And whether implementing OGTT one-hour screening in routine prediabetes care is practical at scale, given that the test is more resource-intensive than a fasting blood draw or HbA1c measurement.

For readers following the tirzepatide evidence base more broadly, the regulatory status and trial programme background are on the tirzepatide page. This analysis adds to the growing literature characterising who benefits most from intensive pharmacologic intervention in prediabetes.