”The understanding of the current findings should be combined with our previously reported clinical results from the SPREAD-DIMCAD study which indicated a beneficial effect of metformin on major cardiovascular events in high risk patients compared with glipizide,” Dr. Yifei Zhang from Shanghai Jiao-Tong University School of Medicine told Reuters Health by email.
In an effort to understand why metformin delivered better outcomes than glipizide, Dr. Zhang and colleagues evaluated the different lipid metabolites in serum samples from 44 patients (23 metformin-treated, 21 glipizide-treated) who participated in SPREAD-DIMCAD.
Among the 118 serum lipid molecular species they identified, two were significantly different between the groups after 1 year of treatment, 11 were different after 2 years of treatment, and 12 were different after 3 years of treatment.
In general, triacylglycerols of a relatively higher carbon number showed a clearly increased trend in the metformin group, whereas changes in triacylglycerols with different double bonds were minimal.
Using a modeling strategy called scaled-to-maximum, aligned, and reduced trajectories (SMART) analysis, metformin substantially affected serum lipid metabolism in type 2 diabetes patients with coronary artery disease, whereas glipizide had only a minimal influence on lipid metabolism, compared with baseline.
When all significantly changed lipid species in all 44 patients were analyzed together, three lipid metabolites – phosphatidylcholine (O-34:1), sphingomyelin (d18:0-24:1), and sphingomyelin (d18:1-20:1) – were associated with long-term composite cardiovascular events, according to the July 10 Diabetes Care online report.
”With the traditional clinical risk factors, we could not explain their differences on the cardiovascular outcomes,” Dr. Zhang said. ”Therefore, the results from the lipidomic analyses added new evidence regarding the underlying mechanisms of disease progression and the effects of different drug therapies on cardiovascular outcomes. On this point of view, we would prefer metformin use in especially high risk type 2 diabetic patients instead of glipizide.”
Not every patient needs a detailed lipidomic profile. ”However, for the following two reasons, we would prefer a lipidomic analysis in our patients with type 2 diabetes: to deeply elucidate and reveal the anti-diabetic drug mechanism on cardiovascular outcomes; (and) to comprehensively understand the metabolic characteristics of cardiovascular high risk patients such as those with diabetes, metabolic syndrome, and dyslipidemia.”
Dr. Zhang added, ”Metabolomics, like other omics techniques, could be a useful platform for clinical researchers to reveal the efficacy and safety of drug therapies, find new therapeutic targets, and discover the underlying mechanisms of disease progression, as well as to help the clinicians to do better health care practice toward their patients.”
Dr. Oscar Giese Laverdy Neto from Medical School Hospital of Sao Paulo University in Brazil has studied lipid metabolism in type 2 diabetes. He told Reuters Health via email, ”CVD deaths account for over 60% mortality in T2D. Interesting results come with this study that shows another good effect of metformin corroborating this drug as first choice in treatment of T2D.”
Like Dr. Zhang, though, he said, ”Lipidomic profile is not suitable for clinical routine.”
Dr. Robert S. Rosenson is Director of Cardiometabolic Disorders at Mount Sinai Hospital, Icahn School of Medicine in New York. He told Reuters Health by email, ”Metformin is favored over glipizide because it reduces cardiovascular events among obese patients. It also has been shown to have minimally favorable changes in lipid values.”
”Lipidomics is a research tool,” Dr. Rosenson said. ”This study suggests that this approach may provide more mechanistic understanding for the differences in cardiovascular outcomes in prior studies with these two classes of agents.”
Diabetes Care 2014 August
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