Efficacy and tolerability of mirogabalin, pregabalin, duloxetine, and placebo in patients with type 2 diabetes mellitus and painful diabetic peripheral neuropathy: A network meta-analysis
In brief
Duloxetine 120 mg reduces diabetic neuropathy pain more than any other tested drug
In a network meta-analysis of 12 trials with 4,542 type 2 diabetics, duloxetine 120 mg achieved the largest pain reduction, outperforming mirogabalin 30 mg and pregabalin. It also showed a better metabolic safety profile, while pregabalin offered only modest relief and higher adverse-effect rates, questioning its role as first-line therapy.
- Journal
- Diabetes research and clinical practice (Q1)
- Published
- 6 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Amber Alam, Taha Alam, Muhammad Saad, Hamdia Gul Aslam, Hamza Sajid, Ghulam Taha Khan, et al.
- PMID
- 42562184
- DOI
- 10.1016/j.diabres.2026.113469
Why clinicians should know about it
- Picked for Anesthesiology and Pain Medicine (top studies of the week, 9 August 2026).
- Picked for Endocrinology, Diabetes and Metabolism (top studies of the week, 9 August 2026).
- Picked for Internal Medicine (top studies of the week, 9 August 2026): Network meta‑analysis of duloxetine, mirogabalin, pregabalin for PDPN
Abstract
Network meta-analysis was conducted to evaluate and compare the efficacy and tolerability of mirogabalin, pregabalin, and duloxetine versus placebo for painful diabetic peripheral neuropathy (PDPN) in type 2 diabetes mellitus (T2DM). PubMed, Embase, Scopus, Cochrane CENTRAL, and ClinicalTrials.gov were searched for randomized controlled trials enrolling adults with T2DM-associated DNP. A frequentist network meta-analysis (netmeta, R) compared standardized mean differences and odds ratios with 95% CI; certainty of evidence was assessed using the GRADE/CINeMA framework. Twelve RCTs (4,542 participants; 2005-2024) were included from 1,587 records. Mean age was 57.7 years; HbA1c 7.6% and moderate baseline pain severity. Duloxetine 120 mg achieved the greatest pain reduction (SMD = -0.60; 95% CI: -0.91 to -0.28; GRADE: high), followed by mirogabalin 30 mg (SMD = -0.39; 95% CI: -0.59 to -0.19). Pregabalin showed only modest benefits (flexible dosing; SMD = -0.21; 95% CI: -0.42 to -0.01). Mirogabalin 30 mg alone achieved a significant > 50% responder advantage (OR = 2.13; 95% CI: 1.18 to 3.85). Pregabalin 600 mg significantly increased adverse effects (OR = 5.89; 95% CI: 2.00 to 17.33); weight gain and edema were elevated with both alpha-2-delta (α2δ) ligands, and somnolence occurred across agents. Within the available short-term evidence network, duloxetine demonstrated the most consistent analgesic efficacy and a more favorable metabolic safety profile than the α2δ ligands evaluated. Pregabalin's modest efficacy and disproportionate burden argue against routine first-line use in T2DM-associated PDNP.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.