Agentes antidiabeticos

REVIEW

Safety and efficacy of nateglinide/metformin combination therapy in the treatment of type 2 diabetes
Marc K Israel 1 Eva Istvan 2 Michelle A Baron 1,3
Novartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA; 2 Novartis AG, Basel, Switzerland; 3 Sanofi-Aventis, Bridgewater, New Jersey, USA
1

Abstract: The increasing prevalence of type 2 diabetes provides impetus for bothdevelopment of new drugs to improve glycemic control and for reconsideration of treatment strategies with existing agents. Combination therapy with complementary drug classes that act on different aspects of glycemic control has been a particularly effective strategy. This work reviews the published literature reporting efficacy and safety/tolerability of nateglinide, a rapid-onset insulinotropicagent with a predominant effect to reduce postprandial glucose, when combined with metformin, a first-line agent that suppresses hepatic glucose production and thereby reduces fasting plasma glucose. The nateglinide/metformin combination has consistently been found to be both efficacious and well tolerated, whether given as initial combination therapy in drugnaïve patients or when added to metforminmonotherapy. Maximum efficacy (Δ glycosylated hemoglobin [HbA1c] = –1.4% to –1.9%, sustained for up to 2 years of treatment) was seen in studies of drug-naïve patients in whom pharmacotherapy was initiated with the combination of nateglinide and metformin, and modest reductions in HbA1c (Δ = –0.5% to –1.2%, sustained for up to 24 weeks) were found when nateglinide was added to ongoing metforminmonotherapy. Conclusion: the combination of nateglinide and metformin provides a sustained degree of glycemic control not achievable with either agent given as monotherapy. Keywords: metformin, nateglinide, combination therapy, type 2 diabetes, postprandial hyperglycemia

Introduction
The total prevalence of diabetes in the United States (both diagnosed and undiagnosed) is estimated to be 7%,representing 20.7 million people (Centers for Disease Control and Prevention 2005). Population models based on data from the National Health and Nutrition Examination Survey (NHANES) project a diabetes burden of 14.5% of the total population (37.7 million people) by 2031 (Mainous et al 2007). Globally, the prevalence of diagnosed diabetes was estimated to be 2.8% in 2000 (171 million people) and isprojected to rise to 4.4% by 2030 (366 million people) (Wild et al 2004). Moreover, it should be recognized that for every 2 people with known diabetes there is another with undiagnosed diabetes. This epidemic of diabetes is driven by Westernization in developing countries, by the increasing prevalence of obesity, and by the aging of the global population (Wild et al 2004). Models based on NHANESand census data project that, at age 18, the lifetime risk of developing diabetes exceeds 50% in obese individuals (body mass index [BMI] 30 but 35 kg/m2) (Narayan et al 2007). The health-care burden that would be imposed by treating the medical consequences of diabetes in such large numbers of patients is enormous and has given impetus

Correspondence: Marc K Israel Novartis PharmaceuticalsCorporation, One Health Plaza 501/336, East Hanover, NJ 07936, USA Tel +1 862 778 3915 Fax +1 973 781 4839 Email marc.israel@novartis.com

Vascular Health and Risk Management 2008:4(6) 1167–1178 © 2008 Israel et al, publisher and licensee Dove Medical Press Ltd. This is an Open Access article which permits unrestricted noncommercial use, provided the original work is properly cited.

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for the development of new drugs to treat type 2 diabetes (T2DM, accounting for 90%–95% of all diabetes) more effectively and to a reconsideration of treatment strategies with existing agents. Diabetes is difficult to control with a single oral agent. Many patients fail to achieve adequate glycemic control (glycosylated hemoglobin [HbA1c] 7.0%) with monotherapy (particularly those...