OBJECTIVE - To examine longitudinal changes in total and appendicular lean body mass in older men with impaired fasting glucose (IFG) or diabetes and to determine whether these changes differ by diabetes treatment. RESEARCH DESIGN AND METHODS - A total of 3,752 ambulatory men aged ≥65 years at baseline participated in amulticenter longitudinal cohort study. Baseline glycemic status was categorized as normoglycemia, IFG, undiagnosed/untreated diabetes, or treated diabetes. Insulin sensitizer medication use (metformin and/or thiazolidinediones) was assessed by prescriptionmedication inventory. The change in total lean and appendicular lean mass was derived from dual X-ray absorptiometry scans taken at baseline and 3.5 ± 0.7 years later. RESULTS - This male cohort included 1,853 individuals with normoglycemia, 1,403 with IFG, 234 with untreated diabetes, 151 with diabetes treatedwith insulin sensitizers, and 111 with diabetes treated without insulin sensitizers. Men with untreated diabetes, diabetes treated without insulin sensitizers, or IFG had greater percentage loss in total or appendicular lean mass (P≤ 0.05 in comparison to normoglycemic men). There remained a significantly greater percentage loss in appendicular lean mass for these groups even after adjustment for medical comorbidities or lifestyle factors. In contrast, the percentage loss in total or appendicular lean mass in men with diabetes treated with insulin sensitizers was significantly less than that in normoglycemic men in minimally and fully adjusted models. CONCLUSIONS - Skeletal muscle loss was accelerated inmen with IFG and diabetes, except when the latter was treated with insulin sensitizers. These findings suggest that insulin sensitizers may attenuate muscle loss. © 2011 by the American Diabetes Association.