Neuropeptide Alterations in Type 2 Diabetes Mellitus: A Meta-Analysis of Circulating Spexin and Galanin Levels.

Spexin and galanin are neuropeptides involved in glucose homeostasis, insulin sensitivity, appetite, and energy metabolism. We conducted a systematic review and meta-analysis to synthesise evidence on circulating spexin and galanin concentrations in patients with type 2 diabetes mellitus (T2DM). PubMed/MEDLINE, Scopus, and Web of Science were systematically searched from inception to March 22, 2026. Observational studies reporting circulating spexin and/or galanin levels in adults with T2DM and non-diabetic controls were included. Random-effects meta-analyses were performed to calculate pooled standardised mean differences (SMDs) with 95% confidence intervals (CIs). Subgroup analyses, meta-regression, sensitivity analyses, prediction intervals, and publication bias assessments were conducted. Nineteen studies met the inclusion criteria. Thirteen studies (1453 T2DM and 850 controls) showed significantly lower circulating spexin levels in T2DM (SMD = -2.37, 95% CI: -3.21 to -1.53; p < 0.0001), with substantial heterogeneity (I2 = 98.3%). Four studies further showed reduced spexin levels in patients with diabetic complications compared with uncomplicated T2DM (SMD = -1.12, 95% CI: -1.75 to -0.49; p = 0.0005). Meta-regression identified age as a significant moderator (p = 0.007), whereas BMI, HbA1c, sex, and publication year were not significant. Four studies (171 T2DM and 172 controls) revealed significantly elevated circulating galanin levels in T2DM (SMD = 1.35, 95% CI: 1.02-1.68; p < 0.0001) with moderate heterogeneity (I2 = 47.2%). Circulating spexin levels are significantly decreased, whereas galanin levels are significantly increased in T2DM. These neuropeptides show potential as biomarkers of metabolic dysregulation and diabetic complications; however, the findings should be interpreted with caution owing to the very low certainty of the available evidence.