Considerations for single- versus multiple-drug pharmacotherapy in the management of painful diabetic neuropathy

ABSTRACT

Introduction

The efficacy of monotherapy to reduce pain from diabetic peripheral neuropathy (DPN) is frequently not satisfactory and guidelines do not provide unanimous treatment options. In this context, multiple drug pharmacotherapy may provide benefit.

Areas covered

The aim of the present review is to describe the clinical trials addressing the pharmacotherapy of painful DPN. Studies discussing efficacy and tolerability of pharmacological agents that were assessed in monotherapy and in combination treatment are reported and discussed.

Expert opinion

Several clinical trials have reported benefit of multiple-drug pharmacotherapy. Nevertheless, untoward effects of combination treatment are of concern. Importantly, some trials were restricted to comparison with placebo and other compared only with active comparator(s). Only limited clinical trials assessed selected cohorts of individuals experiencing different stages of painful DPN. Despite current limitations, some evidence of studies implicating a comparison to all active comparators points to safety and effectiveness of the combination of oxycodone with pregabalin and that of pregabalin with the 5% lidocaine plaster but future, clear-cut studies are required to drive evidence-based decisions in the clinical setting.

KEYWORDS:

• combination therapy
• diabetic peripheral neuropathy
• monotherapy
• neuropathic pain
• treatment

Article highlights

• Monotherapy to reduce pain from DPN is frequently suboptimal and/or characterised by important untoward effects.

• Multi-drug therapy is frequently effective but untoward effects frequently limit its applicability.

• Selected subjects with painful DPN may respond more favourably to combination-treatment and others to high-dose monotherapy.

• Oxycodone plus pregabalin combination and pregabalin plus 5% lidocaine plaster combination can improve pain related to DPN.

• Carefully designed RCTs need to assess the cost-effectiveness and to provide definitive answers on the implementation or rejection of multiple drug pharmacotherapies instead of single agents for the treatment of painful DPN.

This box summarizes key points contained in the article.

Declaration of interest

N Papanas has been an advisory board member of AstraZeneca, Boehringer Ingelheim, Merck Sharp and Dohme, Novo Nordisk, Pfizer, Takeda and TrigoCare International. Furthermore, he has participated in sponsored studies by AstraZeneca, Eli Lilly and Company, GlaxoSmithKline, Merck Sharp and Dohme, Novo Nordisk, Novartis and Sanofi. He has also received honoraria as a speaker for AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Elpen, Merck Sharp and Dohme, Mylan, Novo Nordisk, Pfizer, Sanofi and Vianex and has attended conferences sponsored by TrigoCare International, Eli Lilly, Galenica, Novo Nordisk, Pfizer, and Sanofi. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript has not been funded.