Pharmacokinetics, tolerability, and fructosamine-lowering effect of a novel, controlled-release formulation of alpha-lipoic acid

Endocr Pract. Jan-Feb 2002;8(1):29-35. doi: 10.4158/EP.8.1.29.


Objective: To determine the pharmacokinetics, safety, and tolerability of a novel, controlled-release oral formulation of alpha-lipoic acid (LA) and to investigate whether sustaining the concentration of LA in plasma would have a beneficial effect on glycemic control in patients with type 2 diabetes.

Methods: For the pharmacokinetic study, a single, 600-mg dose of either controlled-release LA (CRLA) or quick-release LA (QRLA) was administered orally to 12 normal human subjects. The plasma profile of LA was determined for 24 hours after administration of the dose,and pharmacokinetic analyses were performed. For the safety and tolerability study, 21 patients with type 2 diabetes were given 900 mg of CRLA daily for 6 weeks, followed by 1,200 mg of CRLA daily for an additional 6 weeks. Active treatment was followed by a 3-week washout period. Throughout the study, patients continued to take their prestudy antidiabetic medications, which included metformin (Glucophage), sulfonylureas (Amaryl, glyburide, and Glucotrol), acarbose (Precose), troglitazone (Rezulin), and insulin (either as monotherapy or in combination). CRLA was evaluated for safety and tolerability as well as for effects on glycemic control.

Results: The Tmax (time to maximal plasma concentration) of LA administered as CRLA was 1.25 hours and was approximately 2.5-fold longer in comparison with the Tmax for QRLA (Tn,5X = 0.5 hour; P<0.02). No severe side effects or changes in either liver or kidney function or hematologic profiles were noted after the administration of CRLA. In 15 patients, the mean plasma fructosamine concentration was reduced from 313 to 283 micromol/L(P<0.05) after 12 weeks of treatment with CRLA.

Conclusion: CRLA increased the plasma concentration of LA over time in healthy subjects, and CRLA was safe, well tolerated, and effective in reducing plasma fructosamine in patients with type 2 diabetes.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acarbose / therapeutic use
  • Aged
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacokinetics
  • Blood Glucose / analysis
  • Chromans / therapeutic use
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / adverse effects
  • Delayed-Action Preparations / pharmacokinetics
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Fructosamine / blood*
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / therapeutic use
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Sulfonylurea Compounds / therapeutic use
  • Thiazoles / therapeutic use
  • Thiazolidinediones*
  • Thioctic Acid / administration & dosage*
  • Thioctic Acid / adverse effects
  • Thioctic Acid / pharmacokinetics*
  • Troglitazone


  • Antioxidants
  • Blood Glucose
  • Chromans
  • Delayed-Action Preparations
  • Hypoglycemic Agents
  • Insulin
  • Sulfonylurea Compounds
  • Thiazoles
  • Thiazolidinediones
  • Fructosamine
  • Thioctic Acid
  • Metformin
  • Troglitazone
  • Acarbose