Efficacy and Safety of Ca

introductionDiabetic peripheral neuropathic pain (DPNP), a chronic complication of diabetes mellitus that impacts quality of life, is treated with Ca

methodsA systematic search was conducted in PubMed, Embase, Cochrane Library, and Web of Science on July 1, 2024 from inception, to identify randomized controlled trials (RCTs) evaluating the efficacy and safety of MGB, PGB, and GBP at various doses for DPNP. Non-RCTs, observational studies, reviews, and case reports were excluded. Eligible studies with data on pain relief, sleep interference, and adverse events were selected. The Cochrane risk of bias tool was used for quality assessment, and a Bayesian hierarchical fixed-effects model was applied using Stata and R software. Primary outcomes were the comparative efficacy of MGB, PGB, and GBP, assessed by changes in average daily pain score (ADPS) and pain response rates (≥ 30% and ≥ 50% pain reduction). Secondary outcomes included comparative effects on were patient global impression of change (PGIC), sleep interference score (SIS), adverse event (AE) rates, and withdrawals due to AEs (WDAE). For continuous outcomes, results were expressed as mean differences (MDs) with 95% credible intervals (CrIs), and for dichotomous outcomes, as odds ratios (ORs) with 95% CrIs within a Bayesian network meta-analysis framework.

resultsIn total, 34 RCTs involving 8630 patients and 13 dosing regimens met the inclusion criteria. The sample size ranged from 40 to 834 and the included RCTs were conducted across multiple countries. MGB 30 mg significantly reduced ADPS compared to PGB 300 mg (Mean Difference (MD) - 0.29; 95% credible interval (CrI) - 0.53 to - 0.05) and MGB 15 mg (MD - 0.32; 95% CrI - 0.64 to - 0.01) and achieved higher pain response rates (≥ 30% and ≥ 50%) than GBP 1800 mg (odds ratio (OR) 2.33; 95% CrI 1.01-5.48 and OR 2.87; 95% CrI 1.14-7.81, respectively). MGB 30 mg and GBP 3600 mg were superior to PGB 300 mg and MGB 15 mg in PGIC scores. MGB 30 mg also demonstrated better SIS improvements over GBP 1800 mg and PGB 300 mg. Fewer AEs occurred with MGB 15 mg, PGB 300 mg, and placebo compared to PGB 600 mg, with MGB 15 mg having the lowest WDAE rates. No significant inconsistency or publication bias was observed.

conclusionsMirogabalin, especially at 30 mg showed superior or comparable pain relief, improved sleep interference, and favorable tolerability for diabetic peripheral neuropathic pain treatment. Ca

trial registrationPROSPERO Identifier: CRD42024584773.