Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus

J Diabetes Complications. Mar-Apr 2007;21(2):118-23. doi: 10.1016/j.jdiacomp.2005.10.005.


Objectives: Metformin is widely used in patients with type 2 diabetes but may decrease vitamin B(12) levels and increase levels of homocysteine (Hcy), a cardiovascular risk factor. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, may reduce markers of inflammation. We investigated whether 6 weeks' treatment with metformin or rosiglitazone affects serum concentrations of Hcy, folate, or vitamin B(12) in subjects with newly diagnosed type 2 diabetes compared with controls.

Methods: We examined 165 patients with type 2 diabetes. Fasting blood samples, a physical examination, and a complete medical history were performed at the beginning and at the end of the treatment. All blood samples were obtained after a 12-h fast.

Results: After treatment, metformin use was associated with an increase in levels of Hcy by 2.36 micromol/l and decreases in folate and vitamin B(12) concentrations by -1.04 ng/ml and -20.17 pg/ml. During rosiglitazone treatment, Hcy levels decreased by -0.92 micromol/l; folate and vitamin B(12) levels remained unchanged. Metformin and rosiglitazone significantly decreased levels of triglyceride (TG), low-density lipoprotein (LDL), total cholesterol (total-C), HbA1c, insulin, and homeostasis model assessment (HOMA). Metformin also significantly decreased body weight. In controls, there was no change in Hcy, folic acid, vitamin B(12), TG, LDL, total-C, HbA1c, insulin, or HOMA levels. Homocysteine change did not correlate with insulin, folate, or vitamin B(12) changes in the metformin and rosiglitazone groups.

Conclusions: In patients with type 2 diabetes, metformin reduces levels of folate and vitamin B(12) and increases Hcy. Conversely, rosiglitazone decreases Hcy levels in this time period. The clinical significance of these findings remains to be investigated.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Blood Glucose / analysis
  • Cholesterol, HDL / blood
  • Cholesterol, HDL / drug effects
  • Cholesterol, LDL / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Fasting / blood
  • Female
  • Folic Acid / blood*
  • Glycated Hemoglobin A
  • Hemoglobins / analysis
  • Homocysteine / blood*
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use
  • Insulin / blood
  • Male
  • Metformin / administration & dosage
  • Metformin / therapeutic use*
  • Middle Aged
  • Rosiglitazone
  • Thiazolidinediones / administration & dosage
  • Thiazolidinediones / therapeutic use*
  • Treatment Outcome
  • Triglycerides / blood
  • Vitamin B 12 / blood*
  • Weight Loss / drug effects


  • Blood Glucose
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Glycated Hemoglobin A
  • Hemoglobins
  • Hypoglycemic Agents
  • Insulin
  • Thiazolidinediones
  • Triglycerides
  • hemoglobin A1c protein, human
  • Rosiglitazone
  • Homocysteine
  • Metformin
  • Folic Acid
  • Vitamin B 12