New Drugs: Breakthrough in the Treatment of Obesity...

New Drugs: Breakthrough in the Treatment of Obesity and Diabetes

A new generation of drugs (polyagonists) represents a decisive breakthrough in the treatment of obesity and type 2 diabetes. Instead of costly surgery, polyagonists help overweight people to significantly reduce their weight and improve their blood sugar levels.

In Germany, well over half of all adult men and women are now overweight. Around 19 million people are even morbidly overweight (obese). Excessive weight is one of the most significant risk factors for type 2 diabetes and cardiovascular disease. For people who are morbidly overweight, stomach reduction surgery has so far often been the only option for losing weight in a targeted manner. An innovative generation of drugs may offer a different possibility: Polyagonists not only drastically reduce weight, but also improve blood sugar levels.

Combination of Hormones

Polyagonists combine the effects of several endogenous hormones. The hormones that are combined in twos or threes are GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent insulinotropic polypeptide) and glucagon. They cause an increased release of insulin, curb the appetite and promote fat loss. The combination of hormones influences several metabolic control centers at the same time.

First New Drug Successful

The first representative of this new class of drugs has already been approved in the U.S.A. and Europe for the treatment of type 2 diabetes and obesity. With impressive successes: Depending on the patient group, the drug tirzepatide reduces body weight by up to 22 percent on average and improves blood sugar levels.

DZD and Helmholtz Munich researchers were among those who developed this innovative effective concept. They are currently working on further polyagonists. Triple polyagonists that combine the effects of the hormones GLP-1, GIP and glucagon and show even stronger effects are currently investigated in clinical studies.

Further Drugs in Development

The use of polyagonists might not only revolutionize the treatment of obesity and type 2 diabetes, but might also become relevant for other diseases. Precise coupling of other hormones makes it possible to target the active ingredients to specific organs and thus minimize potential side effects. DZD researchers are currently developing new polyagonists to improve sugar metabolism and cholesterol levels as well as to reduce body weight and fatty degeneration of the liver.

Publications

Finan B., ..., Tschöp MH. Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans. Sci Transl Med. 2013 Oct 30;5(209):209ra151. doi: 10.1126/scitranslmed.3007218. PMID: 24174327.

Finan B, ..., Tschöp MH. A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents. Nat Med. 2015 Jan;21(1):27-36. doi: 10.1038/nm.3761. Epub 2014 Dec 8. PMID: 25485909.

Tschöp MH, ..., Müller TD, DiMarchi RD. Unimolecular Polypharmacy for Treatment of Diabetes and Obesity. Cell Metab. 2016 Jul 12;24(1):51-62. doi: 10.1016/j.cmet.2016.06.021. PMID: 27411008.

El K, ..., Müller TD, Campbell JE. The incretin co-agonist tirzepatide requires GIPR for hormone secretion from human islets. Nat Metab. 2023 Jun;5(6):945-954. doi: 10.1038/s42255-023-00811-0. Epub 2023 Jun 5. PMID: 37277609; PMCID: PMC10290954.

Liskiewicz A, ..., Müller TD. Glucose-dependent insulinotropic polypeptide regulates body weight and food intake via GABAergic neurons in mice. Nat Metab. 2023 Dec;5(12):2075-2085. doi: 10.1038/s42255-023-00931-7. Epub 2023 Nov 9. PMID: 37946085; PMCID: PMC10730394.

Press contact

Birgit Niesing

niesing(at)dzd-ev.de
+49 (0)89 3187-3971

Dr. Astrid Glaser

glaser(at)dzd-ev.de
+49 (0)89 3187-1619

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