A comparison of the effects of thiazolidinediones and metformin on metabolic control in patients with type 2 diabetes mellitus.
BACKGROUND
Type 2 diabetes mellitus is a condition characterized by impaired insulin secretion and resistance to insulin-mediated glucose uptake and utilization. A number of oral antidiabetic medication are available for its treatment, including metformin and the thiazolidinediones (TZDs). The TZDs have been shown to improve insulin resistance, and it has been suggested that metformin has similar effects. Although both types of agents improve glycemic control, their mechanisms of action and effects on metabolic processes differ.


OBJECTIVE
The goal of this review was to compare the effects of TZDs and metformin on metabolic control in patients with type 2 diabetes.


METHODS
A search of MEDLINE to March 2004 using the terms metformin and biguanides, and thiazolidinediones and glitazones was conducted to identify preclinical and clinical studies focusing on the mechanisms of action and comparative effects of TZDs and metformin. Also searched were published abstracts from recent major diabetes and endocrinology conferences.


RESULTS
In the studies reviewed, both TZDs and metformin demonstrated the ability to improve glycemic control, although long-term monotherapy with TZDs appeared to be more effective than metformin. There continues to be debate about whether metformin is more effective than TZDs in terms of inhibition of hepatic glucose production. However, various studies have found TZDs to be more effective in promoting an increase in whole-body insulin sensitivity. With respect to lipid metabolism, patients who received TZDs had a greater reduction in concentrations of both plasma triglycerides and free fatty acids. Metformin was more effective in promoting weight loss in patients with type 2 diabetes, although TZDs may decrease visceral fat levels. Treatment with either metformin or TZDs was associated with a reduction in the risk of cardiovascular disease, although the mechanisms by which they accomplished this seem to differ.


CONCLUSIONS
The evidence suggests that the predominant effect of metformin is inhibition of hepatic glucose production, whereas the primary effects of TZDs is reduction of insulin resistance and promotion of peripheral glucose uptake. TZDs appear to have more positive effects on other metabolic processes and to be associated with greater improvements in cardiovascular risk factors compared with metformin.
Seufert
Jochen
J
Medizinische Poliklinik, University of Würzburg, Wuerzburg, Germany. j.seufert@mail.uni-wuerzburg.de
Lübben
Georg
G
Dietrich
Karin
K
Bates
Peter C
PC
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D066298:In Vitro Techniques; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008687:Metformin / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome
D001786:Blood Glucose; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D008687:Metformin