Physiological and Biochemical Effects of Intermittent Fasting on Insulin Sensitivity and Glucose Metabolism: A Systematic Review
DOI:
https://doi.org/10.37762/jgmds.13-4.968Keywords:
Intermittent Fasting, Time-Restricted Eating, Insulin Sensitivity, Glucose Metabolism, HOMA-IR, Hbalc, Metabolic Syndrome, Type 2 DiabetesAbstract
OBJECTIVES
This study aimed to review the physiological and biochemical effects of intermittent fasting on insulin sensitivity and glucose metabolism in human studies published between 2019 and 2025.
METHODOLOGY
A literature search was conducted in electronic databases, such as PubMed, Google Scholar, ScienceDirect, SpringerLink, Wiley Online Library and Cochrane Library, for original human studies from January 2019 to December 2025. The studies included in the analysis were randomised controlled trials, randomised clinical trials, open-label randomised trials, randomised crossover trials and prospective interventional trials of intermittent fasting or time-restricted eating. There were no reviews, meta-analyses, narrative articles, case reports, animal or in vitro studies, nor pilot studies. The following data were collected for study characteristics, insulin sensitivity, glucose metabolism, physiological outcomes, biochemical markers, and risk of bias.
RESULTS
Twenty-one original studies were included. Most studies reported favourable effects of intermittent fasting on glucose regulation, fasting insulin, HOMA-IR, HbA1c, continuous glucose monitoring outcomes, body weight, waist circumference, lipid profile, and cardiometabolic markers. Benefits were more consistent among adults with obesity, metabolic syndrome, type 2 diabetes, polycystic ovary syndrome, and increased diabetes risk. Early time-restricted eating and 8–10-hour eating windows showed more promising metabolic effects than less structured fasting patterns. However, the magnitude of benefit varied across studies.
CONCLUSION
Intermittent fasting may improve insulin sensitivity, glucose metabolism, and related physiological and biochemical outcomes, especially in metabolically high-risk adults. However, heterogeneity in fasting schedules, intervention duration, population characteristics, and outcome measures limits direct comparison. Larger long-term randomised trials are needed to identify the safest and most effective fasting protocols.
Downloads
Metrics
References
Joaquim L, Faria A, Loureiro H, Matafome P. Benefits, mechanisms, and risks of intermittent fasting in metabolic syndrome and type 2 diabetes. J Physiol Biochem. 2022;78(2):295-305. doi:10.1007/s13105-021-00839-4. PMID: 34985730 DOI: https://doi.org/10.1007/s13105-021-00839-4
Lu L, Chen X, Liou S, Weng X. The effect of intermittent fasting on insulin resistance, lipid profile, and inflammation on metabolic syndrome: a GRADE assessed systematic review and meta-analysis. J Health Popul Nutr. 2025;44(1):293. doi:10.1186/s41043-025-01039-2. PMID: 40826125; PMCID: PMC12363089 DOI: https://doi.org/10.1186/s41043-025-01039-2
Rajpal A, Ismail-Beigi F. Intermittent fasting and 'metabolic switch': effects on metabolic syndrome, prediabetes and type 2 diabetes. Diabetes Obes Metab. 2020;22(9):1496-1510. doi:10.1111/dom.14080. PMID: 32372521 DOI: https://doi.org/10.1111/dom.14080
Patel S, Yan Z, Remedi MS. Intermittent fasting protects β-cell identity and function in a type-2 diabetes model. Metabolism. 2024;153:155813. doi:10.1016/j.metabol.2024.155813. PMID: 38307325; PMCID: PMC10985623 DOI: https://doi.org/10.1016/j.metabol.2024.155813
Lange MG, Coffey AA, Coleman PC, Barber TM, Van Rens T, Oyebode O, et al. Metabolic changes with intermittent fasting. J Hum Nutr Diet. 2024;37(1):256-269. doi:10.1111/jhn.13253. PMID: 37786321; PMCID: PMC10953463 DOI: https://doi.org/10.1111/jhn.13253
Kramer CK, Zinman B, Feig DS, Retnakaran R. Effect of time-restricted eating on β-cell function in adults with type 2 diabetes. J Clin Endocrinol Metab. 2025;110(6). doi:10.1210/clinem/dgae594. PMID: 39193706 DOI: https://doi.org/10.1210/clinem/dgae594
Pathan MF, Akter N, Mustari M, Saifuddin M, Sharifuzzaman M, Rahman MM, et al. Effectiveness of ertugliflozin during Ramadan fasting in patients with type 2 diabetes mellitus: a real-world study (ErtuRamadan study). Front Endocrinol (Lausanne). 2025;16:1542946. doi:10.3389/fendo.2025.1542946. PMID: 40007804 DOI: https://doi.org/10.3389/fendo.2025.1542946
Jamshed H, Beyl RA, Della Manna DL, Yang ES, Ravussin E, Peterson CM. Early time-restricted feeding improves 24-hour glucose levels and affects markers of the circadian clock, aging, and autophagy in humans. Nutrients. 2019;11(6):1234. doi:10.3390/nu11061234. PMID: 31151228; PMCID: PMC6627766 DOI: https://doi.org/10.3390/nu11061234
Tinsley GM, Moore ML, Graybeal AJ, Paoli A, Kim Y, Gonzales JU, et al. Time-restricted feeding plus resistance training in active females: a randomized trial. Am J Clin Nutr. 2019;110(3):628-640. doi:10.1093/ajcn/nqz126. PMID: 31268131; PMCID: PMC6735806 DOI: https://doi.org/10.1093/ajcn/nqz126
Lowe DA, Wu N, Rohdin-Bibby L, Moore AH, Kelly N, Liu YE, et al. Effects of time-restricted eating on weight loss and other metabolic parameters in women and men with overweight and obesity: the TREAT randomized clinical trial. JAMA Intern Med. 2020;180(11):1491-1499. doi:10.1001/jamainternmed.2020.4153. PMID: 32986097; PMCID: PMC7522780 DOI: https://doi.org/10.1001/jamainternmed.2020.4153
Cienfuegos S, Gabel K, Kalam F, Ezpeleta M, Wiseman E, Pavlou V, et al. Effects of 4- and 6-h time-restricted feeding on weight and cardiometabolic health: a randomized controlled trial in adults with obesity. Cell Metab. 2020;32(3):366-378.e3. doi:10.1016/j.cmet.2020.06.018. PMID: 32673591; PMCID: PMC9407646 DOI: https://doi.org/10.1016/j.cmet.2020.06.018
Kunduraci YE, Ozbek H. Does the energy restriction intermittent fasting diet alleviate metabolic syndrome biomarkers? A randomized controlled trial. Nutrients. 2020;12(10):3213. doi:10.3390/nu12103213. PMID: 33096684; PMCID: PMC7589692 DOI: https://doi.org/10.3390/nu12103213
Guo Y, Luo S, Ye Y, Yin S, Fan J, Xia M. Intermittent fasting improves cardiometabolic risk factors and alters gut microbiota in metabolic syndrome patients. J Clin Endocrinol Metab. 2021;106(1):64-79. doi:10.1210/clinem/dgaa644. PMID: 33017844 DOI: https://doi.org/10.1210/clinem/dgaa644
Che T, Yan C, Tian D, Zhang X, Liu X, Wu Z. Time-restricted feeding improves blood glucose and insulin sensitivity in overweight patients with type 2 diabetes: a randomized controlled trial. Nutr Metab (Lond). 2021;18(1):88. doi:10.1186/s12986-021-00613-9. PMID: 34620199; PMCID: PMC8505293 DOI: https://doi.org/10.1186/s12986-021-00613-9
Li C, Xing C, Zhang J, Zhao H, Shi W, He B. Eight-hour time-restricted feeding improves endocrine and metabolic profiles in women with anovulatory polycystic ovary syndrome. J Transl Med. 2021;19(1):148. doi:10.1186/s12967-021-02817-2. PMID: 33849562; PMCID: PMC8045367 DOI: https://doi.org/10.1186/s12967-021-02817-2
Bartholomew CL, Muhlestein JB, May HT, Le VT, Galenko O, Garrett KD, et al. Randomized controlled trial of once-per-week intermittent fasting for health improvement: the WONDERFUL trial. Eur Heart J Open. 2021;1(2). doi:10.1093/ehjopen/oeab026. PMID: 35919268; PMCID: PMC9241570 DOI: https://doi.org/10.1093/ehjopen/oeab026
Xie Z, Sun Y, Ye Y, Hu D, Zhang H, He Z, et al. Randomized controlled trial for time-restricted eating in healthy volunteers without obesity. Nat Commun. 2022;13(1):1003. doi:10.1038/s41467-022-28662-5. PMID: 35194047; PMCID: PMC8864028 DOI: https://doi.org/10.1038/s41467-022-28662-5
Zhang LM, Liu Z, Wang JQ, Li RQ, Ren JY, Gao X, et al. Randomized controlled trial for time-restricted eating in overweight and obese young adults. iScience. 2022;25(9):104870. doi:10.1016/j.isci.2022.104870. PMID: 36034217; PMCID: PMC9400087 DOI: https://doi.org/10.1016/j.isci.2022.104870
Jamshed H, Steger FL, Bryan DR, Richman JS, Warriner AH, Hanick CJ, et al. Effectiveness of early time-restricted eating for weight loss, fat loss, and cardiometabolic health in adults with obesity: a randomized clinical trial. JAMA Intern Med. 2022;182(9):953-962. doi:10.1001/jamainternmed.2022.3050. PMID: 35939311; PMCID: PMC9361187 DOI: https://doi.org/10.1001/jamainternmed.2022.3050
Andriessen C, Fealy CE, Veelen A, van Beek SMM, Roumans KHM, Connell NJ, et al. Three weeks of time-restricted eating improves glucose homeostasis in adults with type 2 diabetes but does not improve insulin sensitivity: a randomized crossover trial. Diabetologia. 2022;65(10):1710-1720. doi:10.1007/s00125-022-05752-z. PMID: 35871650; PMCID: PMC9477920 DOI: https://doi.org/10.1007/s00125-022-05752-z
Kord Varkaneh H, Salehi Sahlabadi A, Găman MA, Rajabnia M, Macit-Çelebi MS, Santos HO, et al. Effects of the 5:2 intermittent fasting diet on non-alcoholic fatty liver disease: a randomized controlled trial. Front Nutr. 2022;9:948655. doi:10.3389/fnut.2022.948655. PMID: 35958257; PMCID: PMC9360602 DOI: https://doi.org/10.3389/fnut.2022.948655
Teong XT, Liu K, Vincent AD, Bensalem J, Liu B, Hattersley KJ, et al. Intermittent fasting plus early time-restricted eating versus calorie restriction and standard care in adults at risk of type 2 diabetes: a randomized controlled trial. Nat Med. 2023;29(4):963-972. doi:10.1038/s41591-023-02287-7. PMID: 37024596 DOI: https://doi.org/10.1038/s41591-023-02287-7
Pavlou V, Cienfuegos S, Lin S, Ezpeleta M, Ready K, Corapi S, et al. Effect of time-restricted eating on weight loss in adults with type 2 diabetes: a randomized clinical trial. JAMA Netw Open. 2023;6(10). doi:10.1001/jamanetworkopen.2023.39337. PMID: 37889487; PMCID: PMC10611992 DOI: https://doi.org/10.1001/jamanetworkopen.2023.39337
Parr EB, Steventon-Lorenzen N, Johnston R, Maniar N, Devlin BL, Lim KHC, et al. Time-restricted eating improves measures of daily glycaemic control in people with type 2 diabetes. Diabetes Res Clin Pract. 2023;197:110569. doi:10.1016/j.diabres.2023.110569. PMID: 36738837 DOI: https://doi.org/10.1016/j.diabres.2023.110569
Quist JS, Pedersen HE, Jensen MM, Clemmensen KKB, Bjerre N, Ekblond TS, et al. Effects of 3 months of 10-h per-day time-restricted eating and 3 months of follow-up on bodyweight and cardiometabolic health in Danish individuals at high risk of type 2 diabetes: the RESET single-centre, parallel, superiority, open-label, randomized controlled trial. Lancet Healthy Longev. 2024;5(5). doi:10.1016/S2666-7568(24)00028-X. PMID: 38588687 DOI: https://doi.org/10.1016/S2666-7568(24)00028-X
anoogian ENC, Wilkinson MJ, O'Neal M, Laing K, Nguyen J, Van D, et al. Time-restricted eating in adults with metabolic syndrome: a randomized controlled trial. Ann Intern Med. 2024;177(11):1462-1470. doi:10.7326/M24-0859. PMID: 39348690; PMCID: PMC11929607 DOI: https://doi.org/10.7326/M24-0859
Bravo-Garcia AP, Radford BE, Hall RC, Broome SC, Tee N, Arthur B, et al. Combined effects of time-restricted eating and exercise on short-term blood glucose management in individuals with type 2 diabetes mellitus: the TREx study, a randomized controlled trial. Diabetes Res Clin Pract. 2025;222:112081. doi:10.1016/j.diabres.2025.112081. PMID: 40064299 DOI: https://doi.org/10.1016/j.diabres.2025.112081
Oldenburg N, Mashek DG, Harnack L, Wang Q, Manoogian ENC, Evanoff N, et al. Time-restricted eating, caloric reduction, and unrestricted eating effects on weight and metabolism: a randomized trial. Obesity (Silver Spring). 2025;33(4):671-684. doi:10.1002/oby.24252. PMID: 39973006; PMCID: PMC11937878 DOI: https://doi.org/10.1002/oby.24252
Maruthur NM, Pilla SJ, White K, Wu B, Maw MTT, Duan D, et al. Effect of isocaloric, time-restricted eating on body weight in adults with obesity: a randomized controlled trial. Ann Intern Med. 2024;177(5):549-558. doi:10.7326/M23-3132. PMID: 38639542 DOI: https://doi.org/10.7326/M23-3132
Guo L, Xi Y, Jin W, Yuan H, Qin G, Chen S, et al. A 5:2 intermittent fasting meal replacement diet and glycemic control for adults with diabetes: the EARLY randomized clinical trial. JAMA Netw Open. 2024;7(6). doi:10.1001/jamanetworkopen.2024.16786. PMID: 38904963; PMCID: PMC11193124 DOI: https://doi.org/10.1001/jamanetworkopen.2024.16786
Zheng S, Chen Y, Zheng X, Ma D, Yan X, Zhang J, et al. Time-restricted eating plus calorie-restricted diet versus calorie-restricted diet in women with polycystic ovary syndrome. iScience. 2025;28(11):113654. doi:10.1016/j.isci.2025.113654. PMID: 41146709; PMCID: PMC12554142 DOI: https://doi.org/10.1016/j.isci.2025.113654
Ekberg NR, Hellberg A, Sundqvist ML, Hirschberg AL, Catrina SB, Brismar K. The 5:2 diet affects markers of insulin secretion and sensitivity in subjects with and without type 2 diabetes—a non-randomized controlled trial. Int J Mol Sci. 2024;25(17):9731. doi:10.3390/ijms25179731. PMID: 39273678; PMCID: PMC11395907 DOI: https://doi.org/10.3390/ijms25179731
Karras SN, Koufakis T, Adamidou L, Antonopoulou V, Karalazou P, Thisiadou K, et al. Effects of orthodox religious fasting versus combined energy and time restricted eating on body weight, lipid concentrations and glycaemic profile. Int J Food Sci Nutr. 2021;72(1):82-92. doi:10.1080/09637486.2020.1760218. PMID: 32362210 DOI: https://doi.org/10.1080/09637486.2020.1760218
Oueslati I, Kardi A, Boukhayatia F, Hammami B, Cheikh M, Ben Romdhane N, et al. Impact of Ramadan intermittent fasting on metabolic and inflammatory profiles in type 2 diabetic patients. J Diabetes Metab Disord. 2022;21(1):751-758. doi:10.1007/s40200-022-01046-8. PMID: 35673477; PMCID: PMC9167369 DOI: https://doi.org/10.1007/s40200-022-01046-8
Ahmed M, Ahmed MH. Ramadan fasting in individuals with metabolic dysfunction-associated steatotic liver disease, liver transplant, and bariatric surgery: a narrative review. J Clin Med. 2024;13(13):3893. doi:10.3390/jcm13133893. PMID: 38999457; PMCID: PMC11242100 DOI: https://doi.org/10.3390/jcm13133893
Aljaloud KS. The role of lifestyle changes to diet, physical activity, and sleep during Ramadan in controlling metabolic syndrome in adults: a scoping review. J Mens Health. 2024;20(4):1-11. doi:10.22514/jomh.2024.049 DOI: https://doi.org/10.22514/jomh.2024.049
Nofal HA, Elmor AAAER, AbdAllah AM, Zaitoun NA, Andargeery SY, Sharafeddin MA, et al. Effect of intermittent Islamic fasting in management of metabolic syndrome: a randomized control trial. BMC Public Health. 2025;25(1):2476. doi:10.1186/s12889-025-23493-7. PMID: 40670993; PMCID: PMC12265311 DOI: https://doi.org/10.1186/s12889-025-23493-7
Skarstad HMS, Haganes KL, Sujan MAJ, Gellein TM, Johansen MK, Salvesen KÅ, et al. A randomized feasibility trial of time-restricted eating during pregnancy in people with increased risk of gestational diabetes. Sci Rep. 2024;14(1):22476. doi:10.1038/s41598-024-72913-y. PMID: 39341847; PMCID: PMC11439041 DOI: https://doi.org/10.1038/s41598-024-72913-y
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Hina Hakim, Sara Yar Khan, Muhammad Ishraq, Aizazullah, Farzana Salman, Marina Hidayat

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
















