Research has shown that giving obese rodents a recently identified circulating protein called fibroblast growth factor 21 (FGF21) helps improve their metabolism. Now investigators reporting in the Cell Press journal Cell Metabolism reveal that a variant of FGF21 has similar effects in obese people with type 2 diabetes.
"Our findings suggest that FGF21 has the ability to favorably affect body weight and to partially normalize abnormal lipid levels in patients with diabetes. These are substantial issues and unmet medical needs for patients with obesity and type 2 diabetes," says senior author Dr. David Moller, vice president of endocrine and cardiovascular research at Eli Lilly and Company.
Lilly scientists initially identified FGF21 as a novel target for its potential in treating metabolic disorders. Dr. Moller and his colleagues studied the effects of LY2405319 (LY), a variant of FGF21, in a randomized, placebo-controlled, double-blind proof-of-concept trial in 46 patients with obesity and type 2 diabetes. LY treatment led to decreases in LDL cholesterol and triglycerides, increases in HDL cholesterol, and decreases in atherosclerosis-causing lipoproteins.
LY also reduced body weight and fasting insulin, and it increased adiponectin, a hormone produced by fat cells that may augment insulin's effects. While there was only a slight lowering of blood glucose levels in patients treated with LY, the study's results indicate that FGF21 is active in humans and suggest that FGF21-based therapies may be effective for treating metabolic disorders.
"We are encouraged by the potential of FGF21 to produce multiple metabolic effects in people with diabetes and are evaluating further concepts for FGF21-based therapies," says Dr. Moller. He notes that most people with diabetes have other risk factors related to metabolic syndrome, including glucose intolerance, abdominal obesity, elevated triglycerides, low HDL cholesterol levels, and hypertension. No currently available treatment is able to address more than one of these conditions. "Thus, combination therapy is usually prescribed and often leads to tolerability issues, poor patient compliance, and suboptimal outcomes, all of which provide an incentive to continue the search for new therapeutic approaches," Dr. Moller explains.
- Gregory Gaich, Jenny Y. Chien, Haoda Fu, Leonard C. Glass, Mark A. Deeg, William L. Holland, Alexei Kharitonenkov, Thomas Bumol, Holger K. Schilske, David E. Moller. The Effects of LY2405319, an FGF21 Analog, in Obese Human Subjects with Type 2 Diabetes. Cell Metabolism, 2013; 18 (3): 333 DOI: 10.1016/j.cmet.2013.08.005
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