A new clinical study from Lilly Research Laboratories has shown that a single drug can improve insulin intolerance and lower lipid levels in the blood of obese individuals with type-2 diabetes. The results of the clinical trial, published in the journal Cell Metabolism, show that the drug LY2405319 is active in humans and might be an effective therapy for metabolic syndromes such as type-2 diabetes.
Type-2 diabetes is a pathological condition in which glucose levels are higher than normal in the blood. Usually, sufferers of type 2 diabetes cannot properly use insulin, produced by their pancreas, to degrade or store the excess of glucose after each meal. This is called insulin intolerance and is a common consequence of metabolic disorders mediated by obesity. More precisely, obesity and bad metabolism cause the increase of lipids, such as cholesterol and triglycerides.
Current treatment for type-2 diabetes involves a combinatorial strategy and the prescription of several medications as no single drug can treat multiple metabolic markers at the same time. This makes it difficult for many patients to continue therapy. It also causes intolerance leading to ineffective therapy. In search of a single agent that could be used to alleviate most symptoms, Dr. David Moller at Lilly Research Laboratories, led a clinical trial with the compound, LY2405319 (LY). Scientists had previously discovered an important protein, FGF21, for lipid and energy metabolism. When they added more of the FGF21 protein in mice, they saw an improvement in all metabolic symptoms. Therefore, researchers used this information to synthesize LY, an analog of FGF21.
After few initial clinical trials with LY in mice and monkeys, all which showed promising results, Moller and his group performed a randomized placebo-controlled double-blind clinical trial. In this study, 47 patients with obesity and type 2 diabetes were administered various amounts of LY or a placebo every day for 28 days while being subjected to several lab tests during the treatment. The research group monitored every detail of the patients’ the low-density lipoprotein cholesterol (LDL), triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL), atherogenic apolipoprotein levels, body weight, glucose and insulin levels, and metabolic parameters.
Starting early, even from day 2 for some patients, all the parameters in the blood showed improvement; LDL was reduced by 20-30%, triglycerides by 25-46%, fasting insulin levels were also reduced by about 40% suggesting improvement in insulin sensitivity. HDL, the so-called “good cholesterol”, was also increased by about 20% while total cholesterol levels were down by 15-20%.
The study had a few drawbacks. Out of 36 patients who were administered the drug, 3 (about 8%) showed some intolerance and dropped out of the trial. Scientists are now investigating the side effects. Furthermore, as 92% of the patients were of white background, a bigger study should be conducted to evaluate the efficacy of LY in a broader population. However, the study is a big step ahead in the search for a single drug that could improve the life of metabolic syndrome sufferers.