This is a research study of an investigational drug called PB-119. Type 2 diabetes mellitus (T2DM) accounts for 90% to 95% of all diabetes, and is characterized by a decrease in insulin secretion, insulin resistance, and an increase in blood glucose due to increased glucose production in the liver. Diet control and physical exercise are the main methods for the treatment of T2DM patients with a slight increase in fasting blood glucose. If the diet and exercise therapy does not adequately reduce blood sugar, T2DM medications are given.
One medication for T2DM is exenatide (Byetta®, Bydureon®) Exenatide is in a class of drugs called incretin mimetics because these drugs mimic the effects of incretins. Incretins, such as human-glucagon-like peptide-1 (GLP-1), are hormones that are produced and released into the blood by the intestine in response to food. GLP-1 increases the secretion of insulin from the pancreas, slows absorption of glucose from the gut, and reduces the action of glucagon (a hormone that increases glucose production by the liver). All three of these actions reduce levels of glucose in the blood. In addition, GLP-1 reduces appetite. Exenatide is a synthetic (manmade) hormone that resembles and acts like GLP-1. The efficacy and safety of exenatide has been well validated in a wide range of clinical applications and will benefit patients with T2DM. In spite of this, because of the short half-life and the need for frequent injections, patient compliance is anticipated to be the major disadvantage of GLP-1 analogue when competing with DPP-4 inhibitors in the market.
The sponsor has modified exenatide by PEGylation technology. PEGylation is the process of attaching the strands of the polymer PEG to molecules. The PEGylated exanatide is not removed as quickly from the blood and the dosing frequency can be reduced to once weekly. In addition, PEGylation can modify the protein surface, changing the immunogenicity, so as to achieve a reduction in immune adverse reactions.
The purpose of this research study is to compare the effects (both good and bad) and tolerability of PB-119 in research participants with T2DM, not well controlled by Metformin monotherapy. This study will also evaluate how much drug gets into the body and what the body does to the drug (pharmacokinetics or PK). The study drug will be compared to a placebo.