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Randomized Controlled Trial
. 2023 Oct;11(5):e003585.
doi: 10.1136/bmjdrc-2023-003585.

Can earlier biomarker measurements explain a treatment effect on diabetes incidence? A robust comparison of five surrogate markers

Layla Parast  1 , Lu Tian  2 , Tianxi Cai  3   4 , Latha P Palaniappan  5
Affiliations
Randomized Controlled Trial

Can earlier biomarker measurements explain a treatment effect on diabetes incidence? A robust comparison of five surrogate markers

Layla Parast et al. BMJ Open Diabetes Res Care. 2023 Oct.

Abstract

Introduction: We measured and compared five individual surrogate markers-change from baseline to 1 year after randomization in hemoglobin A1c (HbA1c), fasting glucose, 2-hour postchallenge glucose, triglyceride-glucose index (TyG) index, and homeostatic model assessment of insulin resistance (HOMA-IR)-in terms of their ability to explain a treatment effect on reducing the risk of type 2 diabetes mellitus at 2, 3, and 4 years after treatment initiation.

Research design and methods: Study participants were from the Diabetes Prevention Program study, randomly assigned to either a lifestyle intervention (n=1023) or placebo (n=1030). The surrogate markers were measured at baseline and 1 year, and diabetes incidence was examined at 2, 3, and 4 years postrandomization. Surrogacy was evaluated using a robust model-free estimate of the proportion of treatment effect explained (PTE) by the surrogate marker.

Results: Across all time points, change in fasting glucose and HOMA-IR explained higher proportions of the treatment effect than 2-hour glucose, TyG index, or HbA1c. For example, at 2 years, glucose explained the highest (80.1%) proportion of the treatment effect, followed by HOMA-IR (77.7%), 2-hour glucose (76.2%), and HbA1c (74.6%); the TyG index explained the smallest (70.3%) proportion.

Conclusions: These data suggest that, of the five examined surrogate markers, glucose and HOMA-IR were the superior surrogate markers in terms of PTE, compared with 2-hour glucose, HbA1c, and TyG index.

Keywords: biomarkers; biostatistics; diabetes mellitus, type 2; treatment outcome.

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Conflict of interest statement

Competing interests: None declared.

Figures

Figure 1
Figure 1
Cumulative incidence by treatment group, with dashed lines at t=2 years, t=3 years, and t=4 years; the treatment effect at time t, ∆(t), is equal to the distance between the two treatment group curves at each specific time t.
Figure 2
Figure 2
Distribution of marker changes from randomization to 1 year by treatment group, among participants still under observation at 1 year. HbA1c, hemoglobin A1c; HOMA-IR, homeostatic model assessment of insulin resistance; TyG, triglyceride–glucose index.
See this image and copyright information in PMC

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