CALERIE-2 post hoc analysis: weight regain after caloric restriction and insulin–IGF-1 markers
In a post hoc analysis of the 2-year CALERIE-2 trial, participants who regained more than 5% of baseline weight after initial caloric restriction showed reversed improvements in insulin and IGF-1 pathway measures; sustained weight loss kept these benefits and was associated with greater reductions in a biomarker-based estimate of biological age. [1]
Automatic summary · not editorially reviewed
The key findings
The 2-year CALERIE-2 trial randomized 220 participants to 25% caloric restriction or a control diet, with weight loss targeted over the first 6–12 months and a 12-month maintenance phase. [1]
Between months 12 and 24, 20 participants regained more than 5% of baseline weight, and this group had the largest initial caloric reductions. [1]
Weight regain reversed improvements in insulin area under the curve and the IGF-1 to insulin-like growth factor-binding protein 1 ratio, while sustained weight loss was associated with greater reductions in biological age. [1]
The source at a glance
- Study type / format
- Post hoc analysis of a 2-year randomized controlled trial
- Population / context
- 220 adults in the CALERIE-2 trial, with biomarker comparisons in 190 available participants
- Summary based on
- Study abstract
- Original publication
- May 1, 2026
CALERIE-2 trial: 25% caloric restriction versus control diet
The source reports a post hoc analysis of the 2-year CALERIE-2 randomized controlled trial with 220 participants, randomized to 25% caloric restriction or a control diet. The intervention targeted weight loss over the first 6–12 months, followed by a 12-month maintenance phase. For this analysis, participants were stratified by weight trajectory regardless of randomization, and group differences were balanced by propensity score weighting. Cardiometabolic and hormonal markers of 190 available participants, plus a biomarker-based estimate of biological age, were compared across weight trajectory groups.
Supporting source [1]
Weight regain group reversed insulin and IGF-1 improvements
At 12 months, weight loss ranged from 5.0 to 5.8 kg between groups. Between months 12 and 24, most participants maintained weight (n = 112) or continued to lose weight (n = 58), while a smaller group regained more than 5% of baseline weight (n = 20); this group had the largest initial caloric reductions. Weight regain reversed improvements in insulin area under the curve and the ratio of insulin-like growth factor 1 (IGF-1) to insulin-like growth factor-binding protein 1. Sustained weight loss maintained metabolic benefits and was associated with greater reductions in biological age.
Supporting source [1]
Post hoc scope: associations, not proven causes
The authors conclude that substantial weight loss followed by regain can attenuate or reverse caloric-restriction-induced benefits on key regulators of the insulin–IGF-1 nutrient-sensing pathway and markers of biological aging, and that sustained moderate weight loss more effectively improves insulin resistance and maintains favorable hormonal profiles linked to type 2 diabetes risk and aging biology. Because this is a post hoc analysis with participants stratified by weight trajectory rather than by randomization, the comparisons are associations and do not establish that regain causes the observed changes. The abstract does not report effect sizes or confidence intervals for the biomarker comparisons.
Supporting source [1]
How to interpret this
Abstract only; the full text was not reviewed. This is a post hoc analysis in which participants were stratified by weight trajectory regardless of randomization, with propensity score weighting; the comparisons are associations, not causal effects. Effect sizes and confidence intervals for the biomarker comparisons are not reported in the abstract.
Based on the study abstract; the full paper, tables and supplementary data were not reviewed.
Source & supporting passages
Warmbrunn MV, Yang L, Kishore Biswas R, Ryan CP, Harper A, Belsky DW, Fiorito G, Fontana L. · europepmc.org · May 1, 2026