Elsevier

Metabolism

Volume 53, Issue 2, February 2004, Pages 159-164
Metabolism

Effect of metformin treatment on multiple cardiovascular disease risk factors in patients with type 2 diabetes mellitus

https://doi.org/10.1016/j.metabol.2003.07.020Get rights and content

Abstract

In light of the conflicting results of the recent United Kingdom Prospective Study (UKPDS), where diabetic patients on metformin monotherapy had lower all-cause mortality and the addition of metformin in sulfonylurea-treated patients was associated with an increased risk of diabetes-related death, we sought to compare the effects on cardiovascular disease (CVD) risk factors of metformin monotherapy with metformin treatment when added to a sulfonylurea compound in patients with type 2 diabetes. Thirty-one volunteers with type 2 diabetes mellitus, 16 on dietary therapy and 15 on sulfonylurea monotherapy (SU), were treated with metformin for 12 weeks. Measurements were made of (1) fasting plasma glucose, hemoglobin A1c (HbA1c), lipid, remnant lipoprotein cholesterol (RLP-C) levels, and low-density lipoprotein (LDL) particle size; (2) daylong plasma glucose, insulin, free fatty acid (FFA), triglyceride (TG), and RLP-C concentrations; and (3) fasting levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble E-selectin (sE-selectin). Fasting plasma glucose concentrations decreased to a similar degree after treatment with metformin in both the metformin monotherapy group (12.45 ± 0.48 v 9.46 ± 0.47 mmol/L, P < .001) and the combined SU and metformin therapy group (14.09 ± 0.51 v 10.57 ± 0.85 mmol/L, P = .001). Fasting plasma lipid concentrations and LDL particle size did not significantly change in either treatment group, whereas fasting RLP-C concentrations were significantly lower in the metformin monotherapy group (0.43 ± 0.09 v 0.34 ± 0.07 mmol/L, P = .02). Daylong concentrations of plasma glucose, FFA, TG, and RLP-C were lower to a similar degree in both treatment groups, whereas daylong plasma insulin concentrations were unchanged. Fasting plasma sVCAM-1 levels were significantly lower in both the metformin monotherapy group (484 ± 19 v 446 ± 18 ng/mL, P = .02) and the combined SU and metformin therapy group (496 ± 29 v 456 ± 31 ng/mL, P = .05), whereas fasting plasma sICAM-1 and sE-selectin levels were essentially unchanged. Administration of metformin, either as monotherapy or in combination with a sulfonylurea drug, improved glycemic control and led to a decrease in several CVD risk factors in patients with type 2 diabetes.

Section snippets

Materials and methods

The study participants were recruited from the San Francisco Bay area by advertisements in local newspapers indicating our interest in studying risk factors for CVD in hyperglycemic patients with type 2 diabetes mellitus. The Stanford Human Subjects Committee approved the experimental protocol, and each volunteer gave written informed consent. The study was performed at the General Clinical Research Center of Stanford University Medical Center. Thirty-one volunteers with type 2 diabetes, 22 men

Results

Neither blood pressure nor weight changed significantly after metformin treatment in either group. The effect of metformin on glycemic control in the 2 groups is shown in Table 2. It is apparent that both fasting plasma glucose and HbA1c concentrations decreased significantly (P < .01) in both groups. If anything, the decrements in both variables were somewhat greater in those in whom the metformin was added to the SU compound, and in this group the improvement in fasting plasma glucose and HbA

Discussion

Perhaps the most appropriate way to begin discussing our results is to make a clear statement that our findings do not offer an answer to the question whether or not the long-term benefits of metformin treatment vary as a function of its use as monotherapy versus its impact when added to a SU compound in patients with type 2 diabetes in less than optimal glycemic control. There is no doubt that its addition will effectively lower plasma glucose concentrations in SU-treated patients that remain

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  • Cited by (0)

    Supported by Research Grants from the National Institutes of Health (RR-00070 and DK 30732).

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