Abstract
BACKGROUND: Opioids are widely used worldwide for managing acute and chronic pain, yet their systemic effects on metabolic parameters remain unclear. This systematic review and meta-analysis aimed to clarify the impact of opioid use on blood glucose levels and lipid profiles. METHODS: Following PRISMA guidelines, a comprehensive search was conducted in PubMed, Scopus, Web of Science, and Embase databases up to March 2025. Eligible studies included clinical trials and observational studies comparing blood glucose and lipid parameters between adult opioid users and non-users. Pooled mean differences (MDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. RESULTS: Twenty-five studies involving 9,225 opioid users and 27,462 non-users were included. Opioid use was associated with statistically significant but clinically modest reduction in fasting blood sugar (FBS; MD: - 3.00 mg/dl, 95% CI: - 5.71 to - 0.29, p = 0.03), total cholesterol (TC; MD: - 9.06 mg/dl, 95% CI: - 14.63 to - 3.49, p < 0.001), and low-density lipoprotein cholesterol (LDL; MD: - 6.17 mg/dl, 95% CI: - 11.56 to - 0.78, p = 0.02). Subgroup analysis revealed that opium use tended to reduce FBS and LDL levels, while methadone use was linked to higher FBS and TG levels. CONCLUSION: Natural opiates such as opium may slightly lower FBS and LDL levels, whereas synthetic opioids like methadone tend to elevate them. These effects are generally modest and clinically insignificant, providing no evidence of a protective metabolic role for opioids. Clinicians should remain cautious against the misconception that opium use improves metabolic health. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40200-026-01885-9.