糖尿病的治疗进展幻灯片.ppt

* Interest in incretin hormones as a possible avenue toward novel therapy for type 2 diabetes is heightened by the hormones’ potential to enhance β-cell mass. Several lines of experimental evidence suggest that GLP-1 promotes proliferation of existing β-cells,1 an increase in islet size,2 and differentiation of human islet progenitor cells into insulin-producing cells.3 In the study presented here, infusion of GLP-1 to Zucker diabetic rats caused a rise in the number of actively dividing β-cells and an even more striking decline in the number of apoptotic β-cells compared with rats receiving a saline infusion.4 References 1. Xu G, Stoffers D, Habener J, et al. Exendin-4 stimulates both β-cell replication and neogenesis, resulting in increased β-cell mass and improved glucose tolerance in diabetic rats. Diabetes. 1999;48:2270-2276. 2. Stoffers D, Kieffer T, Hussain M, et al. Insulinotropic glucagon-like peptide 1 agonists stimulate expression of homeodomain protein IDX-1 and increase islet size in mouse pancreas. Diabetes. 2000;49:741-748. 3. Abraham E, Leech C, Lin J, et al. Insulinotropic glucagon-like peptide–1 differentiation of human pancreatic islet-derived progenitor cells into insulin-producing cells. Endocrinology. 2002;143:3152-3161. 4. Farilla L, Hui H, Bertolotto C, et al. Glucagon-like peptide–1 promotes islet cell growth and inhibits apoptosis in Zucker diabetic rats. Endocrinology. 2002;143:4397-4408. * * * * * * * DISCUSSION POINTS: Suggest highlighting the top line results of each study then concluding with summary statements: In all three studies, progressive reductions in body weight were seen with both the 10-μg and 5-μg exenatide doses. The greatest weight loss was seen in the exenatide + MET treatment group. SLIDE BACKGROUND: Three 30-week placebo-controlled, double-blind, Phase 3 studies; ITT subjects with type 2 diabetes randomized to placebo (n = 483) or 5 μg (n = 480) or 10 μg (n = 483) exenatide bid with MET and/or SFU, N = 1446. Individu