Background <p>Pasireotide long-acting release (PasiLAR), a somatostatin multireceptor ligand, is effective in achieving biochemical control but can increase the risk of hyperglycemia in acromegaly. However, the impact of PasiLAR on lipid and glucose metabolism in patients with acromegaly has not been systematically studied.&#xa0;This systematic review aimed at synthesizing evidence on PasiLAR effects (as monotherapy or combination therapy with pegvisomant) on lipid and glucose metabolism in patients with acromegaly.</p> Methods <p>MEDLINE, Embase, Cochrane Library, and Web of Science were searched for studies published between 2000 and 2024. Prospective and retrospective studies reporting metabolic outcomes before and under PasiLAR treatment for a minimum follow-up of 6 months. Two reviewers screened eligible publications (3441), extracted outcomes, and assessed risk of bias.</p> Results <p>Nineteen studies (896 patients) were included in the meta-analysis. PasiLAR was associated with increased fasting plasma glucose (FPG) (mean difference [MD] 23.4&#xa0;mg/dL, 95% confidence interval [95%CI] 18.8–28.1]) and glycated hemoglobin (HbA_1c) (MD 0.5%, 95%CI 0.4–0.7). A higher frequency of diabetes mellitus (DM) was observed after treatment (odds ratio 3.7, 95%CI 2.9–4.7). No significant changes in triglycerides, total cholesterol, or low-density lipoprotein cholesterol (LDL-C), and a modest but significant increase in high-density lipoprotein cholesterol (HDL-C) were recorded (MD 6.2&#xa0;mg/dL, 95%CI 1.4–10.9]).</p> Conclusions <p>In this large meta-analysis, PasiLAR was associated with increased HDL-C, FPG, HbA1c, and frequency of DM in patients with acromegaly. There was no effect on triglycerides, total cholesterol, and LDL-C.</p> PROSPERO registration number <p>CRD42024544686.</p>