Weight Regain Reverses Caloric Restriction–Induced Benefits on the Insulin–IGF-1 Nutrient-Sensing Pathway: Post Hoc Analysis From the CALERIE-2 Randomized Controlled Trial
Authors' conclusion
Substantial weight loss followed by weight regain can attenuate or reverse CR-induced benefits on key regulators of the insulin-IGF-1 nutrient-sensing pathway and markers of biological aging. Sustained, moderate weight loss more effectively improves insulin resistance and maintains favorable hormonal profiles linked to type 2 diabetes risk and aging biology.
Study context
- Population
- Participants of the 2-year CALERIE-2 trial randomized to 25% caloric restriction (CR) or control diet190 analysed
- Participants
- 220 participants
- Comparison
- Weight regain vs weight maintenance vs continued weight loss after 1 year of CR
- Maintained weightn = 112
- Continued weight lossn = 58
- Weight regainn = 20
Methodological detailspropensity score weighting, stratified by weight trajectory regardless of randomization
- Propensity score weighting
- Stratified by weight trajectory regardless of randomization
Primary result
As reported in the abstract
Cardiometabolic and hormonal markers and biological age by weight trajectory · months 12 to 24
- Weight regain reversed improvements in insulin AUC and the IGF-1 to IGF-binding protein 1 ratio
- Sustained weight loss maintained metabolic benefits and was associated with greater reductions in biological age
Further findings
Weight loss at 12 months
- Weight loss range between groups
- 5.0 to 5.8 kg
Initial caloric reduction
- Weight regain group had the largest initial caloric reductions
Original publication
Weight Regain Reverses Caloric Restriction–Induced Benefits on the Insulin–IGF-1 Nutrient-Sensing Pathway: Post Hoc Analysis From the CALERIE-2 Randomized Controlled Trial. Diabetes Care. Published 16 March 2026. doi:10.
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