Long-term efficacy of metformin therapy in nonobese individuals with type 2 diabetes.

OBJECTIVE: The U.K. Prospective Diabetes Study (UKPDS) has demonstrated that metformin is as effective as sulfonylureas in obese subjects and is associated with less weight gain, fewer hypoglycemic episodes, and better cardiovascular outcomes. It is hence the pharmacological therapy of choice in this subgroup. However, a gap in our present knowledge is the long-term response to metformin in nonobese individuals. In this study, we compared metformin therapy in normal, overweight, and obese individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A database of patients treated at a referral center in Sydney, Australia, were analyzed. Patients with type 2 diabetes and complete HbA(1c) (A1C) data and treated with metformin or sulfonylurea monotherapy for at least three visits before receiving dual oral therapy were included (n = 644). Analysis by BMI and the type of oral agent was performed. Individuals were categorized as normal, overweight, or obese (BMI <25, 25-29.9, and >/=30 kg/m(2), respectively). RESULTS: There were no differences between the initial, follow-up, and last A1C between the three metformin-treated groups. The duration of successful glycemic control with metformin monotherapy in the normal and overweight individuals and their incidences of diabetes-related complications for the entire duration of follow-up were not inferior to those of the obese individuals. The nonobese patients performed better regardless of the type of oral hypoglycemic agent used. CONCLUSIONS: We conclude that metformin is at least as efficacious in normal and overweight individuals as it is in those who are obese. Our study provides evidence-based data to support metformin use in nonobese individuals with type 2 diabetes.

Meal-related increases in vascular reactivity are impaired in older and diabetic adults: insights into roles of aging and insulin in vascular flow.

A fatty meal induces vasodilatation (of both resting and stimulated forearm flow) in healthy young adults, an effect most likely mediated by the vasodilator actions of insulin. We therefore hypothesized that an impaired meal-related vascular response might be an in vivo marker of vascular insulin resistance, related to the presence of diabetes and/or higher age. Postprandial vascular responses were assessed in three groups of subjects: 15 Type 2 diabetic subjects (age 58 +/- 8 yr), 15 age-, gender-, and body mass index (BMI)-matched older control subjects (age 57 +/- 9 yr), and 15 healthy young control subjects (age 33 +/- 7 yr). Studies were carried out before and 3 and 6 h after a standardized high-fat meal (1,030 kcal, 61 g fat). Forearm microvascular flows were measured by strain gauge plethysmography and large-artery function by ultrasound. Resting blood flow and hyperemic area under curve (AUC) flow were not significantly different in diabetic subjects (resting 117 +/- 42% and AUC 134 +/- 46% of premeal values) compared with age-matched controls (resting 131 +/- 39% and AUC 134 +/- 47%); however, the response in diabetic subjects was blunted compared with young controls (resting 171 +/- 67% and AUC 173 +/- 99% of premeal values; P = 0.02 and P = 0.18, respectively). On multiple regression analysis, we found that increasing age (but not BMI or diabetes) was significantly associated with impaired postprandial vascular responses (resting: r = -0.4, P = 0.002; AUC: r = -0.4, P = 0.006). Therefore, meal ingestion results in impaired vasodilator responses in older nondiabetic and diabetic adults, related to aging rather than insulin resistance.