Diabetes treatment and measures of glycemia.

Incretin treatment Visboll et al. (abstract 1465) studied 13 women with gestational diabetes mellitus during the third trimester and 2–3 months following delivery, showing almost a doubling of the insulin secretory effect of oral glucose over that of intravenous glucose, evidence of reversibility of the reduced incretin effect of type 2 diabetes with improvement in glycemia. Yokoo et al. (abstract 1597) identified a protein, CF266, expressed in the intestine, which increased glucose-stimulated islet insulin secretion and appeared to have -cell trophic effects—perhaps a novel incretin. (Abstract numbers refer to the ADA Scientific Sessions, Diabetes 57 [Suppl. 2], 2008). A number of studies were presented of glucagon-like peptide-1 (GLP-1) receptor activators. Novel formulations are being explored. Asakura et al. (abstract 12) synthesized glycosylated GLP-1 by chemical and enzymatic modifications, showing resistance to degradation by dipeptidyl peptidase-4 with preservation of GLP-1 receptor binding and functional activity and with a 10to 100-fold increase in duration of activity and glucoselowering potency in db/db mice. Blase et al. (abstract 195) administered 60–1,800 g intranasal exenatide in a formulation containing an absorption enhancer to 17 type 2 diabetic patients, finding therapeutic plasma levels and reduction in glycemia after a standardized meal. Although nausea, vomiting, and sneezing occurred in 6, 5, and 2 patients, respectively, this might be an effective therapeutic approach. Costello et al. (abstract 198) admin i s t e r ed GLP-1 adsorbed to Technosphere microparticles by inhalation in 26 healthy individuals, with a rapid increase in plasma GLP-1 to levels 100 pmol/l at 1 and 1.5 mg doses, respectively, increasing insulin and reducing glucose levels. Nausea and vomiting were not reported, although cough and headache occurred. Drucker et al. (abstact 107) treated 295 type 2 diabetic patients with 10 g exenatide twice daily or 2 mg exenatide long-acting release weekly for 30 weeks, finding A1C reductions of 1.5 vs. 1.9% and fasting glucose reductions of 42 vs. 25 mg/dl, respectively, with a mean weight loss of approximatel 4 kg in each group. The currently available formulation of exenatide continues to be a subject of investigation. Brodows et al. (abstract 485) treated 233 drug-naïve type 2 diabetic patients with 5 or 10 mg exenatide or placebo, showing reduction in A1C from 7.8% by 0.7, 0.9, and 0.2%, respectively, with greater weight loss in the groups receiving exenatide. Kendall et al. (abstract 513) presented 2-year follow-up data of 457 type 2 diabetic patients receiving exenatide in combination with metformin, a sul fonylurea, and/or a thiazolidinedione. A total of 156 had early weight loss of 6 kg over the initial 26 weeks, and 210 had more gradual but similar weight loss over the 2-year period. Both groups showed a 1.3% A1C reduction at 2 years, while 91 patients with 1 kg weight gain, although initially having a 1.3% A1C reduction, showed a gradual increase in A1C after the initial 6 months. Recognizing this to be an open-label follow-up, one should presume that the actual rates of weight loss and A1C reduction in clinical practice might not be as favorable. Indeed, Yoon et al. (abstract 482) presented their 2-year follow-up of 192 patients with exenatide added to insulin: 78 discontinued—30 because of side effects, 13 because of a lack of insurance coverage, and 35 for lack of efficacy. A1C decreased 8% from baseline by 0.5– 0.6%. Eleven stopped insulin, and another 11 stopped prandial insulin, with a mean 40% reduction in insulin dose at 6 months, although there was only a 20% reduction in insulin dose at 12–24 months. Loh and Clement (abstract 105) reported their 2-year experience with 30 type 2 diabetic patients treated with exenatide. Weight loss was 3.5 kg at 6 months, 2.1 kg at 1 year, and 1.5 kg at 2 years, and A1C was 7.6% at baseline and at 2 years. Only 11 patients remained on treatment at 2 years, although this group did continue to show improvement in A1C and in weight. Fabunmi et al. (abstract 1213) compared 3,262 patients beginning exenatide with 3,038 beginning insulin glargine in a health plan claim database, finding 68 and 58% adherence, respectively, based on refill rates, with 47 vs. 29% having 80% refill rates while 56 vs. 75% of patients had a 2 month gap between refills, suggesting exenatide to be associated with greater compliance and persistence. However, different sampling policies with the two medications might influence this conclusion because 10g exenatide samples are not offered. Bunck et al. (abstracts 104 and 109) randomized 69 metformin-treated type 2 diabetic patients to addition of exenatide vs. glargine for 12 months and found a 0.8 vs. 0.7% A1C reduction but 3.6 kg weight loss vs. 1 kg weight gain, respectively. The exenatide-treated group had greater arginine-stimulated C-peptide secretion during hyperglycemia at 52 weeks, but after a 4-week washout both groups returned to baseline. Postprandial excursions of both glucose and triglyceride after a standardized meal were reduced with exenatide to a greater degree than with glargine. Liraglutide is a new GLP-1 analog not degraded by dipeptidyl peptidase-4. Noyan-Ashraf et al. (abstract 190) administered liraglutide to mice in a myocardial infarction model, finding reduction in infarct size and improved survival, with increased expression of protective genes, reduction in matrix metalloproteinase 9 expression, and a cardioprotective effect in an isolated heart model. Shimoda et al. (abstract 9) reported a 60% increase in ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ● ●