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Table 2 Clinical studies with ALA in patients with diabetes

From: Alpha-lipoic acid as a pleiotropic compound with potential therapeutic use in diabetes and other chronic diseases


Study type

ALA/other drugs

Analyzed parameters

Total participants

Duration of DM (years)

Follow up (weeks/ years)


Type 2 diabetes treatment

Udupa, AS [134]

Randomized, double- blind placebo-controlled

Vitamin E, omega 3 fatty acids ALA 300 mg All of them daily/orally

Weight, waist glucose

104 with IR

5-10 y

12 w

< HbA1c, weight, waist Better results with omega-3 followed by vitamin E and ALA

Porasuphatana S [135]

Randomized, placebo- controlled

ALA 300 mg -1200 mg/d

HbA1c, FBG


2.07 ± 0.26

24 w

<HbA1c, FBG

De Oliveira AM [136]

Randomized, double- blind placebo-controlled

ALA 600 mg or Vitamin E 800 mg or ALA 600 mg plus Vitamin E 800 mgr

HOMA index, glucose, lipid profile insulin



16 w


Diabetic retinopathy

Haritoglou C [139]

Randomized ,double-blind placebo-controlled

ALA 600 mg/daily

Development of macular edema

232 patients with type 2 and 170 with T1D


86 w

no effect

Nebioso M [140]

Randomized not placebo-controlled

ALA 400 mg daily plus vitamins and genistein




4 w

Improvement in ERG

Diabetic nephropathy

Borcea V [143]

Cross-sectional not placebo-controlled

ALA 600 mg/daily/orally

Lipid ROOH, HbA1c, urine albumin, α tocopherol

107 patients [45 with T1D and 29 with T2D]

21.7 ± 11.1 (with ALA); 15.3 ± 10.4 (without ALA)

>12 w

< ROOH < ROOH/(,α tocopherol/cholesterol The decrease was independent of HbA1c and urine albumin level

Cicek M [144]

Randomized not placebo-controlled

ALA 600 mg/ /orally

CIN Plasma creatinine, Cystation C



Prior coronary angiography

No effect in the incidence of CIN, creatinine, Cystatin C pré /pos exam

Chang JW [145]

Randomized placebo-controlled

ALA 600 mg/orally

Cholesterol, HbA1c C-reactive protein, oxidizedLDL- ADMA

50 patients on hemodyalisis treatment


12 w

Decrease the level of ADMA

Diabetes endothelial dysfunction

Heinisch BB [147]

Randomized, Controlled,double- blind placebo parallel

Daily 600 mg of ALA IV

Endothelial function endothelium dependent and independent HbA1c, lipid profile

30 patients with TD2

7 ± 6

3 w

Improvement in endothelium dependent function

Diabetic cardiovascular autonomic neuropathy

Pop-Busui R [150]

Prospective, randomized, double- blind, placebo- controlled

ALA 600 mg/twice daily Nicotinamide 750 mg/twice daily Allupurinol 300 mg/daily All of them orally

Autonomic tests PET F2 urinary isoprostane HbA1c

44 patients with T1D with mild/moderate cardiovascular autonomic neuropathy and retinopathy or microalbuminuria

27 ± 12

2 y

No improvement in any analyzed parameter

Ziegler D [151]

Randomized, double- blind, placebo- controlled

ALA 800 mg/daily (orally)

Heart rate variability HbA1c Autonomic symptoms

73 patients with T2D

15.3 ± 8.3

16 w

Improvement on root mean square successive difference and power spectrum in low frequency band No difference in the prevalence of symptoms

Diabetic polyneuropathy

ZiegleR D [153] ALADIN I

Randomized,double- blind controlled parallel

ALA:1200 or 600 or 100 mg/daily (orally)


328 patients with T2D with symptomatic peripheral neuropathy


3 w

Improvement in TSS HbA1c: no difference

Reljanovic M [154] ALADIN II

Prospective randomized,double- blind controlled

ALA 1200 mg or 600 mg orally

Sensory and motor nerve function

299 patients (T1D and T2D) with symptomatic polyneuropathy


2 y

Improvement in electrophysiological tests HbA1c: no difference

Ziegler D.[155] ALADIN III

Prospective randomized, double- blind controlled

ALA 600 mg/ IV followed by 1800 mg of ALA or placebo orally


516 patients with T2D with symptomatic polyneuropathy


3 w (IV) 24 w (orally)

No effect HbA1c:no difference

Ametov As [157] Sidney I

Randomized, double- blind ,parallel controlled, mono-center

ALA 600 mg IV


120 (T1D and T2D) with DSPN

15.1 ± 8.8



Ziegler D [158] Sidney II

Randomized, double- blind, parallel controlled, multicenter

ALA 600 to 1800 mg/orally


181 (T1D and T2D) with DSPN




Ziegler D [159] Nathan I

Randomized, double- blind, parallel controlled, multicenter

ALA 600 mg/orally

TSS Composite score( NIS–lower limbs plus 7 neurophisiologic tests (NIS-LL+7)

460 (T1D and T2D) with DSPN


4 years

TSS: no improvement NSI-LL+7:improvement

Ziegler D [160]


ALA 600mg IV



132 months

3 w

Improvement in TSS (papin-prick,touch-pressure), burning,numbness) Improvement in NIS-LL

Mijnhout GS [161]


ALA orally ( 600 to 1800 mg daily) ALA IV (100 to 1200 mg/daily)




3 to 5 w

Improvement in TSS but greater than 30% only in intravenously treated patients

  1. ALA, alpha-lipoic acid; w, weeks; y, years; IV, intravenously; HbA1c, glycated hemoglobin; FBG, fasting blood glucose; HOMA index, homeostasis model assessment; ERG, electroretinogram; ROOH, hidroxiperoxides; CIN, contrast induced nephropathy; ADMA, asymmetric dimethyl-arginine; PET, positron emission tomography; TSS, total symptoms score; NIS, neurophaty impairment score; NIS-LL, neuropathy improvement score of lower limbs; T1D, type 1 diabetes; T2D, type 2 diabetes; IR, insulin resistance; DSPN , distal symmetric sensory-motor polyneuropathy.