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The effect of metformin on blood pressure, plasma cholesterol and triglycerides in type 2 diabetes mellitus; a systematic review
Author(s) -
Wulffelé M. G.,
Kooy A.,
De Zeeuw D.,
Stehouwer C. D. A.,
Gansevoort R. T.
Publication year - 2002
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1046/j.1365-2125.2002.161311.x
Subject(s) - medicine , metformin , blood pressure , diabetes mellitus , type 2 diabetes , randomized controlled trial , stroke (engine) , type 2 diabetes mellitus , insulin , crossover study , medline , clinical trial , endocrinology , placebo , pathology , mechanical engineering , alternative medicine , political science , law , engineering
The UKPD S 34 [1] indicated that intensive treatment with metformin (M) significantly reduces stroke, diabetes‐related endpoints and all‐cause mortality in newly diagnosed type 2 diabetics compared with intensive treatment with insulin or sulfonylurea derivates, despite similar glycaemic control. How this should be explained is yet unclear. Some reports suggested an intrinsic positive effect of M on blood pressure [2] and lipid profile [3]. In an attempt to quantify the effects of M on these parameters we systematically reviewed the literature for randomized controlled trials (RCTs) with M and pooled the obtained data in a meta‐analysis. To identify all RCTs we conducted electronic searches using the bibliographic databases Medline and Embase, contacted the manufacturer and checked the obtained publications for cross‐references. We only included trials with M treatment in type 2 diabetes mellitus of at least 6 weeks. Parallel as well as crossover trials were eligible. Statistical analysis was performed using Review Manager 4.1 and Metaview 4.1. In case data were missing in a specific RCT the investigators were contacted. Of 77 possibly eligible studies, 32 were included in our analyses with a total of 2452 patients. Thirty‐two studies were excluded because the investigators did not or could not provide the desired data and six because of other reasons. Only a small, non‐significant effect was found on systolic and diastolic blood pressure, and HDL cholesterol (−1.37 mmHg, P =0.30; −1.21 mmHg, P =0.10; +0.02 mmol l −1 , P =0.20, respectively). Compared with control treatments M decreased triglycerides, total cholesterol and LDL cholesterol significantly (−0.12 mmol l −1 , P =0.03; −0.20 mmol l −1 , P = 0.0002; −0.25 mmol l −1 , P =0.00001, respectively). We found no indications for publication bias. Of note, glycaemic control was also better with M vs control treatments (−0.80 percent point glyHb; P <0.00001). When studies were subdivided according to tertiles of glycaemic control, it appeared that M had no effect vs control treatments on triglycerides in the tertile where they had similar glycaemic control, whereas in this tertile there still was a significant effect on total and LDL cholesterol. Furthermore, a positive dose‐response relationship was observed between M and total and LDL‐cholesterol. Metformin has no intrinsic effect on blood pressure, HDL cholesterol and triglycerides in patients with type 2 diabetes. Total and LDL cholesterol however, are significantly reduced by this drug, independent of its effect on glycaemia. Whether these latter effects are clinically relevant is questionable considering the limited effect‐size.