Introduction

Type 2 diabetes mellitus (T2DM) is defined as A gradual decline in insulin sensitivity and pancreatic beta-cell function. Evidence-based standardized dietary recommendations for Diabetes mellitus predominantly focused on glycemic index assessment, carbohydrate and calorie intake restriction, and macronutrient balance. While they have therapeutic advantages, adherence to these rules often remains a significant challenge. Insufficient motivation, nutritional fatigue, and issues such as regular dietary intake in their daily activities are common complaints of patients (1). Moreover, typical dietary patterns can lead to the occurrence of weight cycling, deterioration of glycemic instability, and worsening of insulin resistance. These limitations highlight the demand for alternative diets that align with various lifestyle patterns, provide physiological benefits, and promote environmentally conscious behaviors through physical advantages (2). An appropriate diet with potential therapeutic advantages for metabolic diseases, including T2DM, is Intermittent fasting (IF). However, IF a spectrum of eating behaviors identified by intervals of food intake and abstention; it typically does not lead to a reduction in total calories. Typical IF strategies necessitate restricted time eating—particularly the 16:8 strategy, alternate-day fasting, and the 5:2 strategy. In contrast to continuous calorie restriction, IF indicates evidence of influence metabolic pathways via several channels: insulin sensitivity, autophagy activation, hormone modulation, and circadian rhythm synchronization. According to initial studies, IF can influence lipid profiles, assist weight loss, reduce oxidative stress, and raise insulin sensitivity (3).

The findings indicate that IF could be a rational strategy for preserving metabolic activity and disease management for T2DM. Technical and clinical studies demonstrating IF's enhancement of glucose metabolism assist in justification for the growing scientific inquiry into this practice. IF has been demonstrated by rodent models to control hepatic glucose generation, lower systemic inflammation, and improve mitochondrial performance. Although constraints in duration and sample size, human trials have demonstrated promising declines in fasting plasma glucose, body mass index (BMI), and hemoglobin A1c (HbA1c) (4). Furthermore, IF provides cardioprotective benefits, such as reducing blood pressure and lipid levels. Nevertheless, concerns persist about its safety and usefulness among patients using glucose-reducing medications—especially insulin or sulfonylureas— because of the possible risk of hypoglycemia during fasting intervals. The variability of IF protocol designs highlights the demand for standardized approaches and long-term data, which limits direct comparisons and meta-analyses (5).

The objective of this review is to evaluate the present data on the effectiveness of IF in the control of T2DM objectively. It aims to assess the benefits, risks, and limitations of IF in this demographic by aggregating recent studies from clinical trials, mechanistic studies, and observational data. T2DM significantly strains healthcare systems financially; worldwide costs projected in 2021 alone come to USD 966 billion. Rising prevalence is closely associated with lifestyle choices, including physical inactivity, unhealthy eating patterns, and elevated calorie consumption (6, 7). This study comprehensively investigates these elements, strengthening the existing body of knowledge and enabling informed decision-making for patients, doctors, and researchers. With the rising number of people with T2DM and the limits of traditional diet plans, IF provides a practical strategy for enhancing personalized dietary management approaches (8).

Methodology

A comprehensive literature search in the PubMed, Science Direct, Web of Science, and Cochrane databases utilizing Medical Subject Headings (MeSH) and relevant keywords: ‘"Intermittent Fasting “OR "Intermittent Fasting" OR "IF" OR "fasting intervals") AND ("Diabetes Mellitus, Type 2" OR "Type 2 Diabetes" OR "T2DM" OR "Type 2 Diabetes Management” was performed on April 24, 2025. All relevant peer-reviewed articles involving human subjects and those available in the English language were included. Using the reference lists of the previously mentioned studies as a starting point, a manual search for publications was conducted through Google Scholar to avoid missing any potential studies. There were no limitations on date, publication type, or participant age.

Discussion

Pathophysiology of type 2 diabetes mellitus

T2DM develops when peripheral tissues—especially skeletal muscle, liver, and adipose tissue—ineffectively respond to insulin that leads to insulin resistance. Pancreatic beta cells initially act as a compensatory mechanism by increasing insulin secretion. Beta-cell impairment and eventual apoptosis arise from persistent demand. The basic pathophysiology of T2DM is formed by insulin resistance and beta-cell malfunction collectively. Unbalance in glucose and lipid metabolism raises hyperglycemia. Insulin resistance causes an improper increase of hepatic gluconeogenesis, which results in elevated fasting glucose levels (9). Concurrently reduced absorption of glucose by skeletal muscle limits post-prandial glucose clearance. Increased free fatty acids and triglycerides define as impaired lipid metabolism, which promotes ectopic lipid deposition in muscle and liver tissues so reducing insulin signaling. Lipotoxicity disturbs insulin release after the apoptosis of beta cells (10). Two main causes of T2DM are oxidative stress and chronic low-grade inflammation. Adipose tissue releases pro-inflammatory cytokines including TNF-α, IL-6, and MCP-1 in patients resistant to insulin, thus disrupting the pathways of insulin receptor signaling. Induced by mitochondrial malfunction and elevated levels of reactive oxygen species, oxidative stress reduces beta-cell survival and aggravates insulin action. These processes collectively create a complex, integrated network in T2DM, extending hyperglycemia and metabolic malfunction (11).

Overview of intermittent fasting

IF is a pattern of eating behaviors identified by intervals of food intake and abstention, Numerous IF based diets alternate between recommended fasting intervals and unrestricted food intake. While constant calorie restriction (CCR) does not change the meal scheduling, IF does not essentially emphasize the decrease of total calorie intake (12). Common IF diets consist of time-restricted eating (TRF), defined by the 16:8 regimen, involving consumption is restricted to an 8-hour period frequently; alternative-day fasting (ADF), characterized by fasting or minimal caloric intake, usually 25% of daily requirements; and the 5:2 diet (13), permitting unrestricted eating for five days weekly whereas enforcing significant caloric restriction on two non-consecutive days (14). The synchronization of nutrients consumed with circadian cycles and the activation of adaptive cellular processes during fasting periods provide the metabolic justification for IF. By means of a metabolic change from glucose to lipid oxidation, IF generates ketones, so increasing insulin sensitivity (15). Through fasting, it contributes to starting autophagy, a basic mechanism for cellular repair and metabolic efficiency, reducing insulin and glucose levels, and enhancing mitochondrial functioning. Moreover, changing hormonal responses, IF reduces leptin levels and increases adiponectin levels. IF may have a more significant impact on metabolic flexibility and insulin sensitivity than CCR even if total calorie consumption is equivalent (16). Furthermore, due to its organized simplicity and absence of continuous calorie monitoring, some find IF more manageable than CCR (17).

Biological mechanisms of IF in T2DM management

IF significantly modifies insulin sensitivity and glucose homeostasis, thus impacting numerous biological processes associated with the pathogenesis of T2DM. Reduced hepatic insulin resistance and circulating insulin levels allow fasting intervals to promote peripheral organs to absorb greater glucose (18). Reduced hyperglycemia and enhanced glucose clearance in skeletal muscle and adipose tissue by enhanced insulin signaling assists translocation of glucose transporter type 4 (GLUT4) to occur. Typically associated with hormonal changes are the metabolic advantages of IF. Through reducing insulin release during fasting intervals, IF promotes hepatic glycerolizes and lipolysis even as it raises glucagon levels. These modifications facilitate the hormonal balance perturbed in T2 DM to its normal levels (19). Additionally, IF increases circulating adiponectin, an anti-inflammatory adipokine which increases fatty acid oxidation and insulin sensitivity. The subsequent hormonal milieu enhances metabolic control apart from calorie consumption. Furthermore, enhancing mitochondrial performance is IF (20). By means of nutrient shortage, both sirtuin proteins and AMP-activated protein kinase (AMPK) enhance mitochondrial biogenesis and oxidative phosphorylation efficiency. Additionally causing autophagy, a lysosome-mediated degradation mechanism essential for cellular homeostasis, IF facilitates the elimination of damaged organelles and misfolded proteins so preserving beta-cell integrity and reducing lipotoxicity (20). Moreover, IF reduces the expression of pro-inflammatory cytokines and blocks nuclear factor-kappa B (NF-κB), so treating persistent inflammation. The anti-inflammatory impacts enhance insulin efficacy and general metabolic stability, so strengthening the therapeutic possibilities of IF in the treatment of T2DM (21).

Benefits of IF in T2DM

IF has various metabolic advantages for those with T2DM, especially regarding cardiometabolic health and blood glucose control. Standardized IF diets significantly reduce fasting plasma glucose levels, postprandial glucose variations, and HbA1c. More stable glycemic profiles are predominantly ascribed to these enhancements in insulin sensitivity and reduce hepatic glucose production during fasting intervals (22). Furthermore, it contributes to body weight reduction, especially by lowering total fat mass and visceral adiposity. The clinical relevance comes from excess adipose tissue aggravating insulin resistance and systemic inflammation. In contrast to constant calorie reduction, IF encourages a preferred transition to fat oxidation, allowing ongoing fat loss while maintaining lean body mass (23). Additionally, IF contributes to the improvements in cardiometabolic risk factors. Collectively with slight increases in high-density lipoprotein cholesterol, lipid profiles often demonstrate declines in triglycerides and low-density lipoprotein cholesterol. Typically, due to improved vascular function and autonomic modulation, blood pressure lowers (24). Moreover, IF reduces concentrations of C-reactive protein and pro-inflammatory cytokines, so reducing systemically inflammation. Some studies demonstrate that patients following IF regimens—who depend less on insulin and oral hypoglycemics—have a less need for glucose-lowering medications. These findings demonstrate IF's possible non-pharmacological complement value in whole T2DM treatment plans (24).

Risks and considerations associated with IF

Despite its possible benefits, IF presents specific risks that demand cautious management in T2DM. Particularly in those on insulin or insulin secretagogues such sulfonylureas, hypoglycemia is the main clinical issue. If antidiabetic medications are not sufficiently altered, fasting intervals may cause dangerous drop in blood glucose levels. Thus, when implementing IF, patients undergoing pharmaceutical treatment, medical supervision and tailored treatment modifications must be considered. Extended fasting without enough dietary preparation might cause vitamin deficiency (25). Particularly in those with previous nutritional deficits, insufficient consumption of essential vitamins, minerals, and protein over few meals could compromise metabolic health and immunological function (26). Furthermore, limited by psychological and behavioral issues could be adherent to IF guidelines. Some people may experience increased appetite, tiredness, irritability, or disordered eating habits, which would compromise long-term adherence and reduce quality of life. Additionally, dietary patterns in society and culture might make continuous compliance more challenging. Some groups are incompatible for IF (27). Due to increased physiological risk for pregnant or lactating women, those with a history of eating disorders, frail elderly patients, and those with cognitive issues or untreated chronic conditions should not follow intermittent fast diet. To minimize negative impacts and ensure the safe inclusion of IF into customized diabetes treatment plans, thorough screening, patient education, and clinical supervision are indisputably indispensable (28).

Comparison with other dietary interventions

IF diet is among the dietary approaches examined for T2DM. Its efficacy has been set against low-carb diets, ketogenic approaches, and the Mediterranean diet—accepted treatments. High monounsaturated fats, fiber, and antioxidants, the Mediterranean diet has demonstrated time and advantages in glycemic control, lipid management, and lowering of cardiovascular risk. Low-carb and ketogenic diets assist minimizing carbohydrate intake, promoting ketosis and enhanced sensitivity to insulin (27). Additionally, they have demonstrated positive short to medium term glycemic control impacts. Comparatively to these strategies, IF provides similar increases in insulin sensitivity, weight loss, and metabolic markers (29). In contrast to continuous dietary restriction, IF gives meal intervals greatest significance instead of macronutrient composition, so simplifying dietary habits and improving adherence. Furthermore, the reduced clarity in conventional diets are the physiological benefits that IF may provide, including the activation of autophagy and the synchronizing of circadian rhythms (30). Long-term management of diabetes depends much on sustainability. Because of its well defined eating and fasting intervals, certain individuals find IF easier to maintain; others may have trouble with hunger, social dining customs, or rigidity in their daily schedule. The most appropriate nutritional intervention depends much on patient-centered elements including medical comorbidities, lifestyle, dietary preferences, and cultural influences. Understood by clinical supervision, tailored nutritional strategies improve outcomes and compliance in management of T2DM (31).

Clinical implications and recommendations

Adopting IF in the therapeutic management of T2DM necessitates both safety precautions and evidence-based recommendations compliance. Not every patient population would gain from constant application of IF A thorough clinical evaluation is necessary before beginning to review glycemic state, current medication, comorbidities, and individual risk factors—including hypoglycemia or nutritional deficits (32). Medication changes—especially insulin and sulfonylureas—are sometimes required to prevent negative hyperglycemia fluctuations during fasting times. Positive integration of IF depends on customized dietary counseling. Registered dietitians and diabetes educators are absolutely essential in customizing fasting plans to fit patient preferences, metabolic goals, and cultural considerations. Emphasizing balanced macronutrient intake and enough micronutrient levels, nutritional appropriateness throughout feeding periods must be guaranteed. Methodically increasing patient safety and adherence is what meal planning, hydration, and hypoglycemia symptom identification teach (33). Including IF as a complementary component to accepted diabetes treatment—which comprises glucose monitoring, physical exercise, and pharmacological treatment—should contribute to enhance the outcomes. Instead of a one-sided intervention, it should be considered as a component of a whole therapeutic approach. There is constant clinical surveillance needed. Routine follow-up visits must evaluate glucose patterns, anthropometric changes, biochemical markers, and patient-reported outcomes. Through dynamic changes to the diet and early identification of possible problems, this guarantees the safe and effective application of IF in T2DM management (34).

Future research directions

Future studies on IF in respect to T2DM should concentrate on clarifying its long-term consequences, especially for enduring glucose control and possible remission. Although short- and medium-term studies demonstrate improved insulin sensitivity and reduced reliance on medication, data on the sustainability of these outcomes and the ability of IF to support long-term beta-cell maintenance is rare (35). Longitudinal studies with long follow-up are required to determine whether IF can help to reverse diseases or prolong continuous remission. Another crucial focus of study is the identification of biomarkers indicating personal sensitivity to IF. Precision nutrition approaches may be facilitated by stratification of patients based on their potential for metabolic enhancement made possible by metabolic, genetic, and hormonal indicators. These biomarkers could guide protocol choice, improve therapeutic outcomes, and reduce trial-and-error in nutritional treatments (36). There is much research demanded on the combined impacts of IF with medication or regimented exercise. Combining IF with insulin sensitizers or GLP-1 receptor agonists, for example, may increase metabolic efficiency above what monotherapies can accomplish. In a similar manner, combining IF with resistance or aerobic exercise can improve fat oxidation and muscle preservation, so improving general metabolic condition (37). Moreover, later studies should give the involvement of various groups the highest objective. Dietary compliance and metabolic response are much influenced by age, gender, ethnicity, sociocultural background, and so on. In practical diabetic management, developing customized IF strategies catered to demographic and clinical profiles would increase both efficacy and accessibility (38).

Conclusion

IF is a promising non-pharmacological strategy for managing T2DM. It improves glycemic control, insulin sensitivity, and body weight, lowering cardiometabolic risk. Its effects involve hormonal, mitochondrial, and inflammatory mechanisms. Clinical supervision is essential, especially for patients on hypoglycemic drugs. Safety, nutrition, and psychological factors must be addressed. With further evidence, IF may become a useful component of long-term diabetes care.

Disclosures

Author contributions

All authors have reviewed the final version to be published and agreed to be accountable for all aspects of the work.

Ethics statement

Non-applicable.

Consent for publications

Not applicable.

Data availability

All data is provided within the manuscript.

Conflict of interest

The authors declare no competing interest.

Funding

All authors have declared that no financial support was received from any organization for the submitted work.

Acknowledgements

Not applicable.