Exercise modalities and dosages on glycated haemoglobin and exerkines in type 2 diabetes: a systematic review with pairwise, network, and dose-response meta-analyses

BACKGROUND: Exercise is a cornerstone of type 2 diabetes mellitus (T2DM) management; however, the comparative efficacy of specific modalities, optimal dosages, and associated exerkine responses remains incompletely defined. This study aimed to synthesise evidence on the effects of different exercise types and doses on glycated haemoglobin (HbA1c) levels and to explore modality-specific patterns of exerkine regulation in adults with T2DM. METHODS: A systematic review and Bayesian evidence synthesis of randomised controlled trials was conducted up to October 2025. Pairwise, network, and model-based dose-response meta-analyses were employed to evaluate the effects of eight exercise modalities on HbA1c levels. Exploratory analyses were performed to evaluate changes in circulating adiponectin, brain-derived neurotrophic factor (BDNF), interleukin-6, leptin, resistin, and tumour necrosis factor-α levels. RESULTS: A total of 127 trials involving 8,744 participants were included. Network meta-analysis ranked combined mind-body resistance training (tai chi + elastic bands) and high-intensity interval training (HIIT) as the most effective modalities for reducing the level of HbA1c (surface under the cumulative ranking curve: 85.9% and 78.6%, respectively). An L-shaped nonlinear dose-response relationship was observed, with the majority of the clinical benefit being achieved at 600 MET-min/week (mean difference: -0.57%; 95% credible interval: -0.72, -0.42) and a plateau beyond approximately 1,000 MET-min/week. Exploratory exerkine analyses suggested modality-specific signatures; specifically, HIIT was associated with greater increases in adiponectin levels, whereas resistance-based interventions trended towards greater reductions in interleukin-6 and tumour necrosis factor-α levels. In pairwise comparisons versus the control, no significant overall changes were detected for adiponectin, BDNF, interleukin-6, or resistin. CONCLUSION: In adults with T2DM, exercise efficacy varies by modality and follows a dose-plateau pattern. The achievement of 600 MET-min/week produces a meaningful reduction in HbA1c levels, with diminishing returns being observed beyond approximately 1,000 MET-min/week. MBRT and HIIT are the most promising modalities, although the evidence concerning MBRT remains preliminary in nature. Modality-specific exerkine patterns were observed; specifically, HIIT ranked highest for adiponectin, whereas RT ranked highest for IL-6 and TNF-α. These findings inform evidence-based, personalised exercise prescription in T2DM patients.