713-P: Relationship between Magnitude of Weight Loss and Cardiovascular Outcomes in the Diabetes Prevention Program (DPP) and Its Outcomes Study (DPPOS)

Introduction and Objective: Overweight/obesity are determinants of cardiovascular risk. This post hoc analysis evaluated the effect of magnitude of early weight loss during the Diabetes Prevention Program (DPP) on major adverse cardiovascular events (MACE) in DPP and its Outcomes Study (DPPOS). Methods: The DPP randomized 3,234 adults at high risk for type 2 diabetes to intensive lifestyle intervention (ILS), metformin, or placebo (PBO), and subsequently followed the cohort in the DPPOS. Weight loss at DPP Year 1 was assessed categorically (defined as: weight gain/weight neutral (reference category); >0 to <5% weight loss; 5 to <10% weight loss; and ≥10% weight loss). This analysis includes 3,100 participants with Year 1 weight and who did not experience MACE or death prior to Year 1. Time to first occurrence of MACE (death from cardiovascular causes, non-fatal myocardial infarction, non-fatal stroke) during 22 years of follow-up was assessed using log-rank tests. Risk of MACE was assessed with adjusted Cox proportional hazards models and 95% confidence intervals (aHR; 95% CI) in the overall cohort and in separate treatment groups. Results: Time to first MACE differed by weight loss category (p=0.004) in the overall cohort, with the ≥10% loss weight loss category experiencing significantly lower risk of MACE compared with the weight gain/weight neutral reference category (0.59; 0.37 - 0.94). Weight loss of 5 to <10% in PBO was associated with greater risk of MACE compared with weight gain/weight neutral reference category (2.12; 1.19 - 3.76). Conclusion: Overall, a high magnitude (≥10%) of weight loss over 1 year of intervention was associated with lower risk of MACE in a cohort at high risk for type 2 diabetes, but moderate weight loss in the placebo group was associated with greater risk of MACE. These findings may suggest benefits of intervention-related weight loss and increased risks associated with unintentional or unexpected weight loss. Disclosure V.R. Aroda: Research Support; Applied Therapeutics. Consultant; Applied Therapeutics. Research Support; Boehringer-Ingelheim, Corcept Therapeutics. Consultant; Corcept Therapeutics, Pfizer Inc, AstraZeneca. Research Support; AstraZeneca. Consultant; Mediflix, Novo Nordisk. Research Support; Novo Nordisk. Consultant; Sanofi. Research Support; Rhythm Pharmaceuticals, Inc. Consultant; Fractyl Health, Inc. Research Support; Fractyl Health, Inc., Eli Lilly and Company. Other Relationship; Merck & Co., Inc, AditumBio. Research Support; Amgen Inc. N.P. Malkani: None. L. Doherty: None. M.J. O'Brien: None. D. Dabelea: None. U.N. Ibebuogu: None. W.C. Knowler: None. S. Kuo: None. N.N. Mathioudakis: None. S. Edelstein: None. D. Research Group: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (U01 DK048489, U01 DK048339, U01 DK048377, U01 DK048349, U01 DK048381, U01 DK048468, U01 DK048434, U01 DK048485, U01 DK048375, U01 DK048514, U01 DK048437, U01 DK048413, U01 DK048411, U01 DK048406, U01 DK048380, U01 DK048397, U01 DK048412, U01 DK048404, U01 DK048387, U01 DK048407, U01 DK048443, and U01 DK048400)