Predicting the Long‐Term Risk of Type 2 Diabetes and Cardiovascular Disease With Orforglipron in People With Overweight or Obesity: A Post Hoc Analysis of the ATTAIN‐1 Trial
4 affiliations
- 1Eli Lilly and Company Indianapolis Indiana USA
- 2Department of Cardiology, Angiology and Intensive Care Medicine University Hospital RWTH Aachen Aachen Germany
- 3HaaPACS GmbH Schriesheim Germany
- 4University Medical Center Hamburg‐Eppendorf Hamburg Germany
Abstract
Objective: To assess change in long‐term predicted 10‐year cardiometabolic risk (Type 2 diabetes [T2D] and cardiovascular disease [CVD]) in adults with overweight or obesity without T2D.
Methods: This post hoc analysis used data from ATTAIN‐1, a Phase 3 trial in adults (≥ 18 years) with obesity (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2 with ≥ 1 obesity‐related complication) without T2D. Participants received orforglipron 5.5 mg, 9 mg, or 17.2 mg, or placebo for 72 weeks. Changes in predicted risk from baseline to 72 weeks were assessed using three validated risk prediction engines: Cardiometabolic Disease Staging (T2D risk), Framingham (total CVD risk), and PREVENT (total CVD, ASCVD, and HF risk). Mixed models for repeated measures compared change from baseline risk scores between groups.
Results: At week 72, mean relative reduction from baseline (median baseline scores: 16.0%–17.3%) in T2D risk score was significantly greater with orforglipron than placebo (−48.6% to −59.4% vs. −10.5%; p < 0.0001; HR‐range 0.43–0.55). Using Framingham, at week 72, orforglipron was associated with a significant decrease in mean absolute change in total CVD risk vs placebo (−0.6% to −1.00% vs. +0.6%; p < 0.0001; HR range: 0.82–0.87). Similarly, at week 72, orforglipron was associated with reduced predicted ASCVD, HF, and total CVD risks compared to placebo, assessed using PREVENT (p < 0.0001).
Conclusions: In this post hoc analysis, once‐daily oral orforglipron was associated with statistically significant improvements in predicted 10‐year risk of incident T2D and CVD compared with placebo over 72 weeks using three validated risk prediction models.
Trial Registration: ATTAIN‐1: NCT05869903
Related
- Development and validation of a novel metabolic-inflammatory health-related nomogram for predicting in-hospital mortality in older patients with type 2 diabetes mellitus combined with cardiovascular disease
- Reported cardiovascular events and cardiometabolic risk markers with orforglipron and danuglipron in adults with type 2 diabetes or obesity: a systematic review and meta-analysis of randomized trials
- Independent and joint associations of reported household chemical product use and overweight/obesity with cardiovascular disease among older adults in China: a national cross-sectional study.
- Population burden of diabetes, hypertension, and cardiovascular disease attributable to obesity: a community-based study in Türkiye
- Comparative analysis of machine learning and regularized regression models for predicting cardiovascular outcomes in patients with type 2 diabetes after acute coronary syndrome
BibTeX
@article{shinde2026predicting,
title = {{Predicting the Long‐Term Risk of Type 2 Diabetes and Cardiovascular Disease With Orforglipron in People With Overweight or Obesity: A Post Hoc Analysis of the ATTAIN‐1 Trial}},
author = {Shraddha Shinde and Florian Kahles and Simona Vasileva‐Metodiev and Ryan Griffin and Hong Liu‐Seifert and Jeremie Lebrec and Neena A. Xavier and Runjia Li and Suzanne R. Klise and Ambrish Singh and Jens Aberle},
journal = {Diabetes, Obesity \& Metabolism},
year = {2026},
month = sep,
doi = {10.1111/dom.71322},
url = {https://doi.org/10.1111/dom.71322},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Predicting the Long‐Term Risk of Type 2 Diabetes and Cardiovascular Disease With Orforglipron in People With Overweight or Obesity: A Post Hoc Analysis of the ATTAIN‐1 Trial
AU - Shraddha Shinde
AU - Florian Kahles
AU - Simona Vasileva‐Metodiev
AU - Ryan Griffin
AU - Hong Liu‐Seifert
AU - Jeremie Lebrec
AU - Neena A. Xavier
AU - Runjia Li
AU - Suzanne R. Klise
AU - Ambrish Singh
AU - Jens Aberle
PY - 2026
DA - 2026/09/17
JO - Diabetes, Obesity & Metabolism
DO - 10.1111/dom.71322
UR - https://doi.org/10.1111/dom.71322
AB - Objective: To assess change in long‐term predicted 10‐year cardiometabolic risk (Type 2 diabetes [T2D] and cardiovascular disease [CVD]) in adults with overweight or obesity without T2D. Methods: This post hoc analysis used data from ATTAIN‐1, a Phase 3 trial in adults (≥ 18 years) with obesity (BMI ≥ 30 kg/m2) or overweight (BMI ≥ 27 kg/m2 with ≥ 1 obesity‐related complication) without T2D. Participants received orforglipron 5.5 mg, 9 mg, or 17.2 mg, or placebo for 72 weeks. Changes in predicted risk from baseline to 72 weeks were assessed using three validated risk prediction engines: Cardiometabolic Disease Staging (T2D risk), Framingham (total CVD risk), and PREVENT (total CVD, ASCVD, and HF risk). Mixed models for repeated measures compared change from baseline risk scores between groups. Results: At week 72, mean relative reduction from baseline (median baseline scores: 16.0%–17.3%) in T2D risk score was significantly greater with orforglipron than placebo (−48.6% to −59.4% vs. −10.5%; p < 0.0001; HR‐range 0.43–0.55). Using Framingham, at week 72, orforglipron was associated with a significant decrease in mean absolute change in total CVD risk vs placebo (−0.6% to −1.00% vs. +0.6%; p < 0.0001; HR range: 0.82–0.87). Similarly, at week 72, orforglipron was associated with reduced predicted ASCVD, HF, and total CVD risks compared to placebo, assessed using PREVENT (p < 0.0001). Conclusions: In this post hoc analysis, once‐daily oral orforglipron was associated with statistically significant improvements in predicted 10‐year risk of incident T2D and CVD compared with placebo over 72 weeks using three validated risk prediction models. Trial Registration: ATTAIN‐1: NCT05869903
SN - 1462-8902
SN - 1463-1326
ER -