Glycemia-based predictors of T2D development in adults with obesity and prediabetes: SURMOUNT-1 post-hoc analysis

Objective

This post-hoc analysis aimed to assess the predictive value of glycemia-based criteria for development of type 2 diabetes (T2D) among adults with obesity and prediabetes in the three-year SURMOUNT-1 study.

Methods

We evaluated the sensitivity, specificity, positive and negative predictive value of each of the following exploratory criteria for their ability to correctly identify incident T2D cases in the placebo group: Oral Glucose Tolerance Test (OGTT) 1-h glucose ≥155 mg/dL (≥8.6 mmol/L), fasting serum glucose (FSG) ≥ 110 mg/dL (≥6.1 mmol/L), and Hemoglobin A1c (HbA1c) ≥ 6% (≥42.1 mmol/mol).

Results

The OGTT 1-h glucose, FSG, HbA1c based criteria, had a sensitivity of 0.83, 0.50, 0.47, specificity of 0.25, 0.87, 0.69, positive predictive value of 0.15, 0.37, 0.19, and negative predictive value of 0.91, 0.92, 0.90 respectively. Tirzepatide treatment was associated with a 90-99% reduction in new-onset T2D in the high-risk groups, versus 68-91% in the standard risk groups using the three different criteria.

Conclusion

In this post-hoc analysis, we found that OGTT 1-h glucose ≥155 mg/dL (≥8.6 mmol/L) may be a useful criterion to better identify those at high risk of incident T2D. Tirzepatide treatment was highly effective in T2D prevention compared with placebo, regardless of the high-risk criteria used. These findings may guide in the identification of people in whom intensive therapies could be considered to prevent new-onset T2D.

With increasing prevalence of obesity, prediabetes, and undiagnosed type 2 diabetes (T2D), there is an urgency to better identify those at the highest risk of developing T2D and related complications. HbA1c 6-6.4% (42.1-46.4 mmol/mol) and fasting glucose 110-125 mg/dL (6.1-6.9 mmol/L) are associated with higher risk for T2D and diabetic retinopathy and may motivate earlier intervention to prevent T2D (1-3). Oral glucose tolerance test (OGTT) 1 hr glucose ≥155 mg/dL (≥8.6 mmol/L) has been recommended recently by the International Diabetes Federation as a criterion to detect those at high-risk of developing T2D, which in turn may allow for early detection, intervention and improved health outcomes (4-6). However, these glycemic criteria have not yet been examined or implemented widely in adults with obesity and prediabetes.

In this post-hoc analysis of the 3-year SURMOUNT-1 trial, we aimed to compare the predictive value of glycemia-based criteria of developing T2D among adults with obesity and prediabetes. We aimed to evaluate the predictive value of glycemia-based criteria for high-risk for incident T2D among participants in the placebo group and the differences in T2D prevention between tirzepatide and placebo based on these criteria.