Robert C. Frederich

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BACKGROUND The cardiovascular safety and efficacy of many current antihyperglycemic agents, including saxagliptin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, are unclear. METHODS We randomly assigned 16,492 patients with type 2 diabetes who had a history of, or were at risk for, cardiovascular events to receive saxagliptin or placebo and followed them(More)
The regulation of body weight and composition involves input from genes and the environment, demonstrated, for example, by the variable susceptibility of inbred strains of mice to obesity when offered a high-fat diet. The identification of the gene responsible for obesity in the ob/ob mouse provides a new approach to defining links between diet and genetics(More)
BACKGROUND Current perception is that participants of a structured weight-loss program regain all of their weight loss within 5 y. OBJECTIVE The objective was to examine the long-term weight-loss maintenance of individuals completing a structured weight-loss program. DESIGN Studies were required to 1) have been conducted in the United States, 2) have(More)
BACKGROUND Diabetes mellitus and heart failure frequently coexist. However, few diabetes mellitus trials have prospectively evaluated and adjudicated heart failure as an end point. METHODS AND RESULTS A total of 16 492 patients with type 2 diabetes mellitus and a history of, or at risk of, cardiovascular events were randomized to saxagliptin or placebo(More)
beta 3-Adrenergic receptors (beta 3-ARs) are expressed predominantly in white and brown adipose tissue, and beta 3-selective agonists are potential anti-obesity drugs. However, the role of beta 3-ARs in normal physiology is unknown. To address this issue, homologous recombination was used to generate mice that lack beta 3-ARs. This was accomplished by(More)
The mutant gene responsible for obesity in the ob/ob mouse was recently identified by positional cloning (Zhang Y., R. Proenca, M. Maffel, M. Barone, L. Leopold, and J.M. Friedman. 1994. Nature (Lond.) 372:425). The encoded protein and to represent and "adipostat" signal reflecting the state of energy stores. We confirm that the adipocyte is the source of(More)
Modafinil is indicated for the management of excessive daytime sleepiness; however, recent studies have examined a broad range of potential uses. Given that clinical uses of modafinil may be expanding, this study compared modafinil and d-amphetamine effects on subjective and performance measures. Across 11 sessions, 11 healthy adults were tested after oral(More)
Despite efforts to achieve a desirable weight, two-thirds of the population has an elevated body weight. Medications are useful in supporting weight loss, but produce adverse effects. This study compared the effects of amphetamine and modafinil on food intake and cardiovascular activity in healthy men and women. Participants (n = 11) completed 11 sessions.(More)
Leptin is synthesized exclusively by adipocytes and acts on the hypothalamus to regulate energy balance. Previous messenger RNA expression studies demonstrated that leptin is expressed in white adipocytes and also in brown adipose tissue, however expression in brown fat is markedly lower than in white fat. This suggests the possibility that leptin(More)
OBJECTIVE The objective was to assess the relative risk (RR) for cardiovascular (CV) events across all 8 randomized phase 2/3 trials evaluating saxagliptin in patients with type 2 diabetes mellitus. METHODS Cardiovascular events (death, myocardial infarction [MI], stroke, revascularization procedures, and cardiac ischemia) were reported by investigators(More)