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Clinical Research

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

International Journal of Obesity (2026)Cite this article

Subjects

Abstract

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.

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Fig. 1: Reported mealtime on 24-h food records on 3 alternate days during each intervention period.
Fig. 2: Hormonal profile in response to oral glucoe challenge.
Fig. 3: Hormonal profile in response to oral glucoe challenge.
Fig. 4: Changes in subjective appetite assessed by a 0–100 mm visual analog scale between baseline and intervention end point for each intervention period: standard lifestyle and time-restricted eating (TRE).

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Data availability

De-identified data can be made available under restricted access from the corresponding author, for academic purposes, subject to a material transfer agreement and approval of the Mount Sinai Hospital Research Ethics Board.

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Acknowledgements

The corresponding author (CKK) had full access to all the data in the study and had final responsibility for the decision to submit for publication. This study was supported by the Canadian Institutes of Health Research (CIHR) (PJT 166091) (CKK). RR holds the Boehringer Ingelheim Chair in Beta-cell Preservation, Function, and Regeneration at Mount Sinai Hospital. The funders had no role in study design, data collection and analysis, or writing of the manuscript.

Funding

This study was supported by the Canadian Institutes of Health Research (CIHR) (PJT 166091) (CKK). RR holds the Boehringer Ingelheim Chair in Beta-cell Preservation, Function, and Regeneration at Mount Sinai Hospital. The funders had no role in study design, data collection and analysis, or writing of the manuscript.

Author information

Authors and Affiliations

  1. Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, Canada

    Caroline K. Kramer, Bernard Zinman, Denice S. Feig & Ravi Retnakaran

  2. Division of Endocrinology, University of Toronto, Toronto, ON, Canada

    Caroline K. Kramer, Bernard Zinman, Denice S. Feig & Ravi Retnakaran

  3. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada

    Caroline K. Kramer, Bernard Zinman, Denice S. Feig & Ravi Retnakaran

Authors
  1. Caroline K. Kramer
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  2. Bernard Zinman
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  3. Denice S. Feig
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Contributions

CKK, RR and BZ designed the study. CKK and RR acquired the data. CKK led study implementation, performed the statistical analyses, and wrote the manuscript. CKK, BZ, DF and RR contributed to the interpretation of the data and critical revision of the manuscript. CKK, BZ, DF and RR approved the manuscript.

Corresponding author

Correspondence to Caroline K. Kramer.

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Competing interests

All authors declare no competing interests related to the submitted work. CKK reports research grants from Boehringer Ingelheim, outside of the submitted work. DSF reports an investigator-initiated grant from Dexcom, in-kind donations from Dexcom and Tandem and honoraria from Novo-Nordisk, Sanofi and Ypsomed, outside the submitted work. RR reports grants from Boehringer Ingelheim, grants and personal fees from Novo Nordisk, personal fees from Sanofi, personal fees from Eli Lilly, outside the submitted work. All other authors declare no competing interests.

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Kramer, C.K., Zinman, B., Feig, D.S. et al. The effects of time-restricted eating on energy balance regulation in adults with overweight/obesity and type 2 diabetes. Int J Obes (2026). https://doi.org/10.1038/s41366-026-02042-1

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