1 BETA-CELL FAILURE IN DIABETES AND PRESERVATION BY ...
1 BETA-CELL FAILURE IN DIABETES AND PRESERVATION BY ...
1 BETA-CELL FAILURE IN DIABETES AND PRESERVATION BY ...
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61<br />
mathematical model. In a similar study over 52 weeks of vildagliptin added to metformin<br />
treated DM2, an improvement was demonstrated in beta-cell function, with enhanced<br />
postprandial insulin secretion, increased insulin sensitivity and “dispostion index”. Twelve<br />
week treatment of drug-naïve DM2 with vildagliptin (50 mg bid) restored the acute insulin<br />
response to glucose (AIRg) and sensitivity index(Si) determined by FSIVGTT. The<br />
disposition index (AIRg x Si) increased >4-fold and part of its effect remained after 2-4<br />
week washout, suggesting that vildagliptin may exert some disease-modifying effect. Three<br />
recent studies have been carried out in the same line as for sitagliptin. One study compared<br />
vildagliptin (50mg bid) monotherapy with metformin over 52 weeks, with better sustained<br />
control with the DPP-IV inhibitor. In the second study, vildagliptin (50 mg qd or bid) was<br />
added to metformin with improvement of glycemic control slightly better with the larger<br />
dose. The third study compared vildagliptin (100 mg qd) with placebo in insulin-requiring<br />
DM2. After 24 weeks, there was a reduction in HbA1c and in the mean insulin doses.<br />
Single-dose studies indicate that sitagliptin and vildagliptin have similar clinical<br />
efficiency in reducing the glucose excursion after oral glucose.Data are not yet available to<br />
enable comparison of the efficacies of both products in chronic use.<br />
Potential effects on preservation and augmentation of β-cell mass<br />
Regarding the most important question concerning both GLP-1 analogs,<br />
GLP-1R activators and DPP-IV inhibitors(incretin enhancers) – incretin mimetics - is<br />
whether they will be able to slow or prevent the apparently inevitable progress of the<br />
DM2,considering their trophic effects on beta-cells (249), not only stimulating their<br />
proliferation (185, 250) but also enhancing the differentiation of new beta-cells from<br />
progenitor cells in the pancreatic duct epithelium (251) and, perhaps most importantly,<br />
being capable of inhibiting apoptosis of the beta cells including human beta cells (195).<br />
Since the normal number of beta-cells is maintained in a balace between apoptosis and<br />
proliferation, the protective effects of incretin mimetics could be relevant under conditions<br />
in which beta-cell apoptosis is increased, such as in DM2 (4). Since, for obvious reasons, it<br />
is difficult to estimate the protective effects of incretin mimetics on beta-cells in humans<br />
there is no clinical evidences that these drugs really have protective effects on beta cells