UK-based Pharmaceutical Profiles has used an imaging technique known as scintigraphy to quantify the effects of Amylin / Eli Lilly’s latest diabetes drug on the stomach.
The study found that Byvetta (exenatide) considerably decreases the speed of gastric emptying (GE) and indicates that it is a key contributing mechanism of the beneficial effects of exenatide on postprandial (post meal) glycaemia.
There are nearly 250 million people worldwide who suffer from diabetes, according to the International Diabetes Federation (IDF), with the global diabetes drug market being valued at $15bn (€10.4bn) in 2005 and expected to grow to over $22bn by 2012.
Type 2 diabetes affects over 9 per cent of the US population is characterised by either low levels of, or an inadequate response to insulin - a hormone secreted by the pancreas to release energy from the breakdown of carbohydrates.
Exenatide is a 39-amino acid peptide and is one of a new class of diabetes medications known as incretin mimics.
It is a synthetic version of the exendin-4, a hormone found in the saliva of the Gila monster and displays biological properties similar to human glucagon-like peptide-1 (GLP-1) that regulates glucose metabolism and insulin secretion.
The drug is believed to work in at least four ways, which include: increasing insulin secretion that helps lower blood sugar level increases in response to eating; suppressing pancreatic release of glucagon which stops hyperglycaemia, reducing appetite; and slowing GE.
However, until the recent study the significance of the slowing of GE had not been quantified.
Scintigraphy is acknowledged as the gold-standard method for the assessment of GE and involves taking a two-dimensional picture of a body using radioisotope imaging to gain a quantitative view of various processes occurring within the body.
The data generated helps to elucidate the potential for drug-drug interactions and evaluate the pharmacodynamic effect of drugs that influence gastric kinetics.
In this study, the Pharmaceutical Profiles team used the technique to simultaneously measure the GE of solids and liquids and assess the distribution of contents within the stomach of seventeen subjects suffering from Type 2 diabetes.
“Uniquely, scintigraphy provides a complete picture of gastric emptying, showing clearly what is happening with a drug,” said Andy Rankin, chief scientific officer at Pharmaceutical Profiles.
“In today’s increasingly competitive market, generating quantitative data early in the development process informs decisions, saves time and money, and adds value to a candidate drug.”
This particular study further substantiated statements on the product label regarding reduction of the rate at which glucose appears in the circulation after meals with the administration of exenatide.
In each 5-day period, 5 or 10 µg exenatide or placebo was administered subcutaneously by intravenous drip and on day 5, after the morning dose, subjects consumed a 450-kcal breakfast containing 99mTc-labelled eggs and 111In-labelled water, and GE was measured by scintigraphy.
The study showed that taking 5 µg of exenatide nearly doubled the average residence time of solids in the stomach from 60 minutes to 111 minutes. Taking 10 µg of exenatide increased this figure to 169 minutes.
The residence times for liquids where increased further still, with those taking a placebo having liquids in their stomachs for an average of 34 minutes, those taking 5 µg of exenatide an average of 87 minutes and those taking 10 µg of exenatide 114 minutes.
Taking exenatide reduced postprandial by 69–76 per cent and peak insulin by 84–86 per cent compared with placebo.