Narcolepsy and metabolic disease: A meta-analytic synthesis

Narcolepsy is a chronic neurological disorder marked by sleep-wake dysregulation and an elevated burden of endocrine and metabolic comorbidities. However, evidence on specific metabolic outcomes across narcolepsy subtypes remains heterogeneous. We conducted a systematic review and meta-analysis (PROSPERO CRD42024576070) to primarily quantify the prevalence and risk of metabolic syndrome (MetS) in narcolepsy, with additional cardiometabolic conditions assessed as secondary outcomes. Five databases were searched through April 8, 2025, included 54 studies after screening. Pooled prevalence estimates and odds ratios were derived using random-effects model, with subgroup analyses by narcolepsy type, age, sex, orexin deficiency, HLA-DQB1∗06:02 positivity, and treatment status. Obesity emerged as the most common comorbidity (30%), followed by diabetes, hypertension, and dyslipidemia (each 10% - 20%). MetS prevalence reached 30% but was notably higher in adult NT1 (59%). NT1 was susceptible to prediabetes (27%) and non-dipping blood pressure (54%). Sensitivity analyses indicated greater cardiometabolic burden in NT1, males, and orexin-deficient individuals. Pediatric patients largely exhibit obesity, while overweight increased with age. Collectively, these findings underscore a substantial cardiometabolic risk profile in narcolepsy (particularly NT1). This elevated prevalence highlights the clinical importance of incorporating routine metabolic screening and consistent monitoring into their standard care framework, independent of specific treatment choices.