Cardiac Metabolomic Alterations in Diabetes: Interplay with Lipoprotein Lipase—A Systematic Review

We conducted a systematic review on cardiac metabolomic alterations in type 2 diabetes and the interplay with lipoprotein lipase (LPL). To synthesize evidence on LPL activity, cardiac metabolomics, and cardiovascular outcomes in type 2 diabetes. EMBASE, PsycINFO, AMED, LILACS, and Web of Science were searched from January 2000 to August 2025; last searches: EMBASE [22 August 2025], PsycINFO [22 August 2025], AMED [22 August 2025], LILACS [22 August 2025], Web of Science [22 August 2025]. Original human studies in type 2 diabetes reporting cardiac metabolomics and LPL activity; no language restrictions. Two reviewers independently screened records/reports and extracted data; risk of bias was assessed with RoB 2 (randomized trials), ROBINS-I (nonrandomized studies), and the Newcastle–Ottawa Scale (observational). We planned random-effects meta-analyses using mean difference/standardized mean difference or risk ratio, quantified heterogeneity with I2 and τ2, examined small-study effects with funnel plots/Egger’s test, and rated certainty with GRADE. We included 11 studies (n = 541). LPL modulation was associated with improved triglycerides, LDL-C, HDL-C, and selected metabolomic markers; heterogeneity ranged I2 = [97–99]%. Heterogeneous metabolomic platforms and LPL assays; several small observational studies. The review was registered in PROSPERO, ID: CRD42025632960.