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Metformin Improves Metabolic Control and Other Physiologic Variables in Type 2 Diabetes

Treatment of type 2 diabetes with metformin effectively lowers blood glucose levels, benefits lipid profiles, improves vascular and haemodynamic indices, and is generally well tolerated, report researchers.

Stephen M. Setter, PharmD, CDE, DVM, Washington State University, Spokane, United States, and colleagues conducted a comprehensive literature review of the pharmacology, pharmacokinetics, adverse effects, drug-interaction potential, dosing guidelines, clinical efficacy and safety, and pharmacoeconomics of the biguanide agent metformin hydrochloride.

Available in Europe since the 1950s, metformin was only approved for use in the US in 1994; in October 2000, it was approved in an extended-release (XR) formulation that combined metformin with glyburide, rosiglitazone, or glipizide.

As the only currently available oral antidiabetic and hypoglycaemic agent that acts primarily by inhibiting hepatic glucose release, metformin has been shown to effectively lower blood glucose levels and improve lipid profiles. When used as monotherapy or combined with other agents, metformin is associated with a 1% to 2% reduction in glycosylated haemoglobin (HbA_1c).

Clinical data based on a number of well-designed randomised trials confirm the metabolic control and improvements in lipids and vascular parameters achieved by metformin alone or in combination. Emphasised in this review is the efficacy of dual therapy, given in the form of separate agents (metformin plus a thiazolidinedione, a "glitinide," or an alpha-glucosidase inhibitor) or as a combination agent (metformin plus a sulfonylurea).

Overall, metformin is well tolerated with mostly transient gastrointestinal adverse effects - the most common event occurring in up to 50% of the patients. Lactic acidosis is the most serious side effect; though rare (about 8 cases in 100,000 person-years), it causes death in 50% of the patients who develop it.

Based on these data, the authors conclude that "with the recent introduction of combination products containing metformin and rosiglitazone or a sulfonylurea, health care providers have an expanded array of therapies for the management of type 2 diabetes."

Clin Ther 2003 Dec;25:12:2991-3026. "Metformin hydrochloride in the treatment of type 2 diabetes mellitus: A clinical review with a focus on dual therapy"

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