Antidiabetic tandem
By combining the molecules of two antidiabetic drugs, scientists have increased their effectiveness
A study by scientists from Duke University has shown that the effectiveness of combination therapy using two well-known drugs against type 2 diabetes increases if these drugs are not just administered to the patient at the same time, but their molecules are connected by a thermosensitive bond.
The drugs in this study were glucagon-like peptide-1 (GLP-1) and fibroblast growth factor 21 (FGF21). GLP-1 is usually produced by the human intestine after eating. It enhances the release of insulin from the pancreas and promotes weight loss. But high doses of this substance, which are necessary in some cases of diabetes to maintain normal blood sugar levels, sometimes cause gastrointestinal upset. Therefore, scientists are looking for combined methods to minimize side effects by combining GLP-1 with other drugs.
"FGF21 operates by a different mechanism than GLP-1, and we assumed that these two drugs would complement each other well," says Caslin Gilroy, one of the authors of the work. – GLP-1 increases insulin secretion by the pancreas, while FGF21 enhances the body's response to insulin. GLP-1 reduces food intake, and FGF21 helps burn more calories."
But the researchers did not just inject two drugs into mice at the same time, but tried to combine GLP-1 and FGF21 into a single molecule. The link between them was an elastin-like polypeptide. When injected under the skin, it forms a gel that slowly dissolves and releases molecules of both substances. The effect of one injection on laboratory mice with diabetes lasted more than a week, the experimental drug provided glucose control and weight loss. "Binding drugs to an elastin–like peptide allows us to create a compound that is liquid at room temperature, but forms a gel-like depot after injection," explains Gilroy. "It dissolves for at least a week, slowly and regularly releasing the drug."
In the experimental group of mice, the concentration of the drug in the blood remained stable, and the sugar level decreased to normal for 10 days after a single dose. Mice treated with the GLP-1/FGF21 combination drug stabilized their sugar levels faster after glucose injection compared to those who received the drugs individually or only one of the two drugs. They were also the only test group that lost weight during the experiment.
The authors of the study believe that such a method can be effective in the treatment of other diseases.
The results are published in the journal Science Advances (Gilroy et al., Sustained Release of a GLP-1 and FGF21 Dual Agonist from an Injectable Depot Protects Mice from Obesity and Hyperglycemia).
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