In Obese Subjects With Type 2 Diabetes, Are Short-Acting Insulin Analogs That Short?
Ardilouze JL, et al.
Because insulin absorption depends on blood flow in adipose tissue (ATBF) and ATBF is 40%-70% lower in obese subjects, the goal of this study was to test whether or not short-acting insulin preparations (in this study, insulin lispro) have a delayed absorption in obese patients with type 2 diabetes. In controls, the results were consistent with published data. In obese patients with type 2 diabetes, plasma levels of insulin lispro were blunted at low doses and severely delayed at higher doses, suggesting that the timing and effectiveness of shot-acting insulin preparations need to be re-evaluated in obese patients with type 2 diabetes.
Pharmacokinetic and Pharmacodynamic Effects of Oral GLP-1 and PYY3-36: A Proof of Concept Study in Healthy Subjects
Beglinger C, et al.
Currently available formulations of GLP-1 require subcutaneous administration. This study tested an oral preparation of GLP-1, as well as an oral preparation of the satiety peptide PYY3-36. In this single center dose-escalation study, 6 males subjects received one of the following doses of oral GLP-1 (.5, 1, 2, and 4 mg) or placebo. Another 6 males were randomly assigned to receive either PYY3-36 in one of the following doses (.25, .5, 1, 2, and 4 mg) or placebo. Oral administration of both peptides yielded a dose-dependent and rapid increase in drug concentration. Additionally, oral GLP-1 was associated with a significant increase in insulin release, and PYY3-36 was associated with a trend toward ghrelin suppression. Although this was a small study, it is important because it is the first to show that satiety peptides can be delivered orally in humans.
Initial Combination Therapy With Sitagliptin and Metformin Provides Effective and Durable Glycemic Control Over 1 Year in Patients With Type 2 Diabetes
Williams-Herman DE, et al.
Because initial monotherapy in type 2 diabetes is often not successful in meeting glycemic targets, the goal of this study was to test initial monotherapy with metformin and sitagliptin, compared with either sitagliptin or metformin monotherapy. After a placebo-controlled 24-week trial, patients continued on a 30-week active-controlled trial. Patients who were randomly assigned to pharmacotherapy in the initial 24-week study continued on their treatment (sitagliptin 100/metformin 2000 [S100/M2000], sitagliptin 100/metformin 1000 [S100/M1000], metformin 2000 [M2000], metformin 1000 [M1000], and sitagliptin 100 [S100]). Patients initially assigned to placebo were switched to M2000 for the active-control portion of the study. Metformin only conditions were delivered as 2 daily divided doses, and sitagliptin monotherapy was delivered once daily. These results reflect patients who received active treatment for the 52-week duration. In the analysis of all patients treated, mean changes from baseline A1C were -1.8% for S100/M2000, -1.4% for S100/M1000, -1.3% for M2000, -1% with M1000, and -.8% for S100. Changes were higher for completers. The incidence of hypoglycemia was low across treatment groups.
Development and Testing of a Novel Platform for Measuring Multiple Biomarkers in Serum Samples Demonstrated in 5-Yr Prospective Study of Progression to Type 2 Diabetes (Inter99)
Kolberg J, et al.
Because earlier identification of type 2 diabetes could potentially impact morbidity and mortality, this study developed and tested an ultrasensitive protein detection method to assist in this goal. Using data from the Inter99 study, molecular counting technology (MCT) was used to compare people who progressed to type 2 diabetes (converters) with nonconverters. In each subject, 18 serum protein biomarkers were assessed. Univariate analysis of data collected demonsted that 6 biomarkers highly correlated with conversion to type 2 diabetes. The biomarkers that correlated with conversion are known to affect carbohydrate and lipid metabolism, inflammation, coagulation, and complement cascade. These biomarkers were predictive of conversion to type 2 diabetes over and above known risk factors for type 2 diabetes. |
