MD Conference Express EASD 2012 - (Page 23)

O T H E R n E w s n The Challenges of Pharmaceutical Management of Painful Diabetic Peripheral Neuropathy Written by Rita Buckley Diabetic peripheral neuropathy (DPN) affects up to 50% of patients with diabetes and is a major cause of morbidity and increased mortality. Its clinical manifestations, which include painful neuropathic symptoms and insensitivity, increase the risk for burns, injuries, and foot ulceration [Tesfaye S, Selvarajah D. Diabetes Metab Res Rev 2012]. Solomon Tesfaye, MD, University of Sheffield, Sheffield, United Kingdom, discussed findings from recent studies on pharmaceutical agents used to treat DPN. Medication for diabetic peripheral neuropathic pain (DPNP) includes tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs; eg, duloxetine), anticonvulsants (eg, pregabalin), opiates, membrane stabilizers, the antioxidant α-lipoic acid, and others. New agents that might have fewer side effects have emerged over the past 7 years [Tesfaye S, Selvarajah D. Diabetes Metab Res Rev 2012]. However, current treatments still provide suboptimal pain relief. Questions about the management of DPNP center on the best first-line drug, the best combination of first-line drugs, whether to switch or combine various agents, the nature of a clinically meaningful response for monotherapy, length of time to determine efficacy, and whether to prescribe an early combination of drugs that work by different mechanisms versus a trial of maximum doses of monotherapy. One study found that gabapentin and morphine combined achieve better analgesia at lower doses of each drug than either as a single agent, with constipation, sedation, and dry mouth being the most frequent adverse effects [Gilron I et al. N Engl J Med 2005]; another study reported that coadministration of prolonged-release oxycodone and existing gabapentin therapy has a clinically meaningful effect on DPNP [Hanna M et al. Eur J Pain 2008]. A randomized, double-blind, crossover trial compared the efficacy and safety of amitriptyline versus pregabalin in painful diabetic neuropathy. Pregabalin 150 mg BID was associated with fewer adverse effects than amitriptyline (Table 1) [Bansal D et al. Diabet Med 2009]. A Study in Painful Diabetic Neuropathy [COMBO-DN; Tesfaye S et al. Submitted; EUCTR 2009-010063-16-DE] was the largest double-blind randomized trial to date on combination treatment for DPNP. It investigated the efficacy of a combination treatment of duloxetine plus pregabalin compared with the maximal dose of each drug in monotherapy in patients with DPNP (Figure 1). As such, it addressed a common clinical question: Is it better to increase the dose of the current monotherapy or combine both treatments early in patients who do not respond to standard doses of duloxetine or pregabalin? Table 1. Amitriptyline Versus Pregabalin in DPNP. Improvement Good (VAS > 50% reduction) Moderate (25%-50%) MIld (<25%) PGIC, MPQ Likert PS Adverse events Amitriptyline % 34 11 27 no difference 65.4 Pregabalin % 48 13 15 no difference 34.6 (p<0.01) DPNP=diabetic peripheral neuropathic pain; MPQ=McGill Pain Questionnaire; PGIC=Patient Global Impression of Change; PS=point scale; VAS=visual analog scale. Figure 1. COMBO-DN Initial Treatment Period (8 Weeks). Enrolled: n=1074 Randomized: n=811 Randomized and treated: n=804 Duloxetine 60 mg/day n=401 Pregabalin 300 mg/day n=403 Discontinuations n=68 (17.0%) Adverse effects n=35 Responders n=164 (40.9%) Discontinuations n=70 (17.4%) Adverse effects n=39 Responders n=116 (28.8%) Reproduced with permission from S. Tesfaye, MD. The trial did not clearly demonstrate that standard dose combination therapy of duloxetine with pregabalin provides significantly better pain relief compared with high-dose monotherapy of either drug in DPNP patients with insufficient pain relief. There was no evidence that safety and tolerability are negatively affected when duloxetine is combined with pregabalin in these patients. For initial treatment, duloxetine (60 mg/day) provided better analgesia than pregabalin (300 mg/day). 23 Peer-Reviewed Highlights of the 48th Annual Meeting of the European Association for the Study of Diabetes 

Table of Contents for the Digital Edition of MD Conference Express EASD 2012

MD Conference Express EASD 2012
Contents
Understanding Incretin Hormone Action and the Treatment of Diabetes
New ADA/EASD Guidelines Focus on Patient-Centered Care
ORIGIN Trial: Insulin Glargine and n-3 Fatty Acids Fail to Reduce CV Events in Diabetic Patients
Exenatide Once Weekly Sustained Improvement in Glycemic Control with Weight Loss Through 4 Years
DiaPep277® Shows Promise as a Therapeutic Strategy for T1DM
Linagliptin Proves Safe and Effective as Add-on Therapy to Basal Insulin
12-Week Treatment with LY2409021 Significantly Lowers HbA1C and Is Well Tolerated in Patients with T2DM
Insulin Degludec Is Superior to Sitagliptin in Improving Glycemic Control in Uncontrolled Patients with Type 2 Diabetes on Oral Agents
Dapagliflozin Does Not Impact Renal Function in Patients with T2DM
Population-Based Screening for T2DM:The ADDITION-Cambridge Trial
The Challenges of Pharmaceutical Management of Painful Diabetic Peripheral Neuropathy
Enterovirus Infection
Novel Oral Agents
GLP-1
Genetics
Renal Denervation
Hypertension and Renal Function Are Risk Factors for CAD in T1DM

MD Conference Express EASD 2012

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