Page 96 - The lraternational Journal of the Royal Society of Thailand.indd

The International Journal of the Royal Society of Thailand
Volume XV-2023

Treatment
Pathogenetic based treatment

Several compounds in various groups were investigated but many of them were
unsuccessful such as aldose reductase, inhibitors, prostacyclin analogs, nerve growth
factors, vascular endothelial growth factor, protein kinase C inhibitors, vitamin E, etc.

Alpha lipoic acid which reduce oxidative stress had more extensive studies
showing benefit in symptomatic relief and may counteract the PDN pathogenesis.

It is initially tested with intravenous formulation and later with oral formulation.
Most are short term studies which showed significant pain reduction , based on various
measures. It may slow down the disease progression, based on one large long-term
study of four-year duration. It has been registered as an approved medication in this
indication in many countries and it is also available as nutritional supplement. Recent

studies showed promising data of new aldose reductase inhibitors (epalrestat,
ranirestat), alpha lipoic acid and benfotiamine. Further studies are underway for
short- and long-term efficacy and safety information (Ziegler et al, 2021; Abubaker

et al, 2022).
Benfotiamine is also another interesting alternative. It is a synthetic prodrug of

thiamine with rapid and excellent absorption. It activates transketolase activities and
finally inhibits AGE formation. Many diabetic patients with coexisting diseases such
as malnutrition or chronic renal failure may have subclinical thiamine deficiency and

they are prone to have polyneuropathy from nutritional deficiency. Benfotiamine at
the dose of 300-600 mg/d has been shown in short-term studies to reduce neuropathic
pain. It may be combined with other medications without significant side effects. Their
side effects are comparable to placebo group. Both carry no significant interaction with
other drugs or underlying diseases. Long-term studies are being performed (Ziegler

et al, 2021). Recent meta-analysis concluded that B vitamins should be considered a
plausible therapy for diabetic neuropathy, but its overall efficacy remains uncertain
and requires further study (Karaganis & Song, 2021).

Symptomatic treatment for painful diabetic neuropathy

Assessment of pain and its effect on function and quality of life should be
performed before any treatment. When initiating pharmacologic intervention for PDN,
clinicians should counsel patients that the goal of therapy is to reduce, and not

necessarily to eliminate, pain. Clinicians should assess patients with PDN for the
presence of concurrent mood and sleep disorders and treat them as appropriate.
Individualized approach is recommended to use may factors for drug selection, such

88 Revisiting Diabetic Polyneuropathy and Autonomic Neuropathy