International Journal of Obesity · Mar 11, 2026

The effects of time-restricted eating on energy balance regulation in adults with overweight/obesity and type 2 diabetes

By Kramer CK, Zinman B, Feig DS et al.

BACKGROUND/OBJECTIVES: Time-restricted eating (TRE) induces a metabolic shift in substrate utilization increasing lipolysis and ketogenesis. These metabolic changes raise the possibility of a differential effect on energy balance regulation following TRE-induced weight loss. The aim of this study is to evaluate the impact of TRE on energy balance homeostasis in individuals with overweight/obesity and type 2 diabetes (T2DM) who participated in a recently reported trial achieving substantial weight reduction (-3.86% body weight). SUBJECTS/METHODS: In this randomized cross-over trial, 39 participants with overweight/obesity and T2DM were randomized to either 6 weeks of TRE (20 h fasting/4 h eating) or standard lifestyle, followed by 4-week washout and then the other dietary intervention for 6 weeks. At each study visit at baseline, 6-, 10-, and 16-week participants completed a 75 g oral glucose tolerance test (OGTT). We measured fasting and post-challenge responses of glucose, glucagon, GLP-1, ghrelin, leptin, and peptide YY. RESULTS: TRE-induced calorie deficit as participants self-reported ingested -384 ± 488 Kcal/day less during TRE as compared to the standard lifestyle period (P < 0.001) with no differences in macronutrient distribution. There were no differences in responses to OGTT induced by TRE as compared to standard lifestyle for glucagon (AUC0-120 min 0.04 ± 23.5, P = 0.99), GLP-1 (AUC0-120 min 1.6 ± 67.6, P = 0.98), ghrelin (AUC0-120 min 31.0 ± 32.4, P = 0.35), and peptide YY (AUC0-120 min -33.9 ± 65.6, P = 0.61). Importantly, TRE-induced weight loss promoted a significant decrease in both fasting leptin (-2445 ± 885 ng/mL, P = 0.009) and leptin response to OGTT (AUC0-120 min -12776 ± 3088, P < 0.001) as compared to standard lifestyle. In addition, a significant increase in fasting ghrelin (28 ± 11.3 pg/mL, P = 0.02) was observed post-TRE as compared to pre-intervention. CONCLUSIONS: These findings demonstrate that TRE does not prevent the physiologic compensatory changes associated with weight reduction in individuals with overweight/obesity and T2DM.

doi.org/10.1038/s41366-026-02042-1PubMed 41814085Interventions