The use of hypoglycemic drugs in Parkinson's disease: An updated meta-analysis of randomized controlled trials

Recent studies have demonstrated an association between hypoglycemic medications and neuroprotective action in neurodegenerative diseases, such as Parkinson's disease (PD). Therefore, in this meta-analysis, our objective was to evaluate the efficacy of these medications, compared to placebo, as disease-modifying therapy in patients with PD. We systematically searched PubMed, Embase, and Cochrane for studies comparing the use of hypoglycemic drugs and placebo in patients with PD. Statistical analyses were performed using R Studio 4.3.2. Mean difference (MD) with 95 % confidence intervals (CI) were pooled across trials. Outcomes of interest were change in Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS) parts I, II, III, IV, and Parkinson's Disease Questionnaire 39 (PDQ-39). This meta-analysis included six randomized controlled trials (RCT) reporting data on 787 patients. Among them, 480 (61 %) received hypoglycemic drugs. Follow-up ranged from 36 to 61 weeks. At the end of follow-up, improvement in MDS-UPDRS part III score during OFF state occurred when subjects received any hypoglycemic agents at their lowest dose (MD -1.36; 95 % IC -2.78 to −0.47; I2 = 38 %), as well as highest doses (MD -1.58; 95 % IC -3.07 to −0.09; I2 = 50 %). Changes in MDS-UPDRS part III score in patients examined in the ON state who received any dose of any hypoglycemic agents (MD -3.32; 95 % IC -5.28 to −1.36; I2 = 0 %) were significant. There was no significant difference between groups MDS-UPDRS parts I, II, IV, and PDQ-39. In patients with PD, the use of hypoglycemic agents showed efficacy on symptomatic PD treatment with an improvement in MDS-UPDRS part III. •Hypoglycemic drugs significantly improve motor symptoms (MDS-UPDRS III) in Parkinson's disease.•In addition to symptomatic benefits, these drugs show potential as modifiers of PD.•Although common, the adverse events of these drugs are mild to moderate and manageable.•The use of hypoglycemic agents, GLP-1 analogs and glitazones, compared to placebo, has efficacy and safety in PD patients.