Combination Therapy in Diabetic Neuropathy

A high percentage of diabetic patients develop peripheral neuropathy with more than 10 % suffering from severe symptoms. Therapeutic alternatives for diabetic sensorimotor polyneuropathy (DSPN) have so far involved pathogenesis oriented or symptomatic treatments. These two therapeutic approaches differ in their effects: the former aims to reverse, halt or delay progression of neuropathic damage, while the latter aims to relieve neuropathic pain and its associated secondary consequences without impact on the underlying neuropathic process. Most guidelines recommend symptomatic treatments to alleviate the complaints associated with DSPN. Tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors, and alpha(2)-delta ligands are frequently mentioned as first-line drugs for painful diabetic peripheral neuropathy. However, new evidence points to pathogenesis-oriented treatments based on alpha-lipoic acid or benfotiamine as promising therapeutic alternatives to classical purely symptomatic treatments. A few new trials have reported an advantage of combination therapies versus single-drug administration, but the limited extent of studies on specific combinations together with design flaws in these studies have caused reluctance in recommending combination therapy as a first treatment option in guidelines. However, combination therapy stands as a powerful instrument for DSPN treatment based on the positive evidence accumulated and the otherwise common use of multidrug treatments in clinical diabetic neuropathy.