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Asrar MM, Kumari S, Sekhar BC, et al. Relative Efficacy and Safety of Pharmacotherapeutic Interventions for Diabetic Peripheral Neuropathy: A Systematic Review and Bayesian Network Meta-Analysis. Pain Physician. 2021 Jan;24(1):E1-E14. (Systematic review)

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a most common devitalizing complication of diabetes mellitus, which is primarily characterized by sensory loss, paresthesia, prickling, pain, or allodynia.

OBJECTIVES: To evaluate the relative efficacy and safety of the interventions used in the DPN pain management and rank their order.

STUDY DESIGN: A systematic review and Bayesian network meta-analysis (NMA).

METHODS: Randomized, controlled trials were identified through a comprehensive, systematic literature exploration, primarily utilizing the PubMed, EMBASE, Ovid, and Cochrane Library databases. The efficacy and safety outcomes consist of the proportion of patients reporting either 30% or 50% pain reduction and overall withdrawal or withdrawal due to adverse drug events, respectively. Effect estimates from Bayesian NMA were presented as odds ratio (OR) with 95% credible intervals (CrI). Heterogeneity and convergence were assessed by using I2 and deviation information criteria. The risk of bias was evaluated by using Pedro Scale.

RESULTS: A total of 3,246 potentially relevant trials were identified and screened, finally 43 trials consisting of 7,877 randomized patients met the inclusion criteria. Statistically significant treatment difference for 50% pain reduction was reported for duloxetine vs. placebo (OR: 2.50; CrI: 1.62-3.91), mirogabalin vs. placebo (OR: 3.25; CrI: 1.16-9.35), pregabalin vs. placebo (OR: 2.33; CrI: 1.69-3.27), duloxetine vs. carbamazepine (OR: 3.37; CrI: 1.07-10.90), mirogabalin vs. carbamazepine (OR: 4.39; CrI: 1.01-19.63), mirogabalin vs. lamotrigine (OR: 4.05: CrI: 1.07-15.77), pregabalin vs. lamotrigine (OR: 2.90, CrI: 1.19-7.22) and pregabalin vs. nortriptyline (OR: 4.10, CrI: 1.13-5.28). Nortriptyline reported the highest possibility of achieving 30% and 50% pain reduction. Sodium valproate and benztropine reported the highest probability of total withdrawals and withdrawals due to adverse drug events, respectively.

LIMITATION: The different follow-up time of the included studies can result in the variation of intended results.

CONCLUSION: Nortriptyline reported the advantage relative to other drugs in achieving 30% and 50% pain reduction from the baseline. Gabapentin reported a significance of 50% pain reduction relative to placebo.

Discipline Area Score
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Neurology 5 / 7
Endocrine 5 / 7
Internal Medicine 5 / 7
Comments from MORE raters

Endocrine rater

This review supports the benefit of older agents for peripheral neuropathy over newer, more expensive agents.

Internal Medicine rater

This is an interesting study, but the results are confusing for nortriptyline, duloxetine, and pregabaline.

Neurology rater

This is a very helpful summary of numerous studies of therapeutic interventions in diabetic neuropathy. The statistical analysis is helpful in planning treatment for patients.
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