Emerging Treatments of Diabetes Complications

Coordinators:

Stephan Herzig | Annette Peters | Julia Szendrödi | Robert Wagner

Members of the Academy

Ferruh Artunc, IDM
Alexander Bartelt, LMU
Mauricio Berriel Diaz, HMGU
Matthias Blüher, Leipzig
Gidon Bönhof, DDZ
Bilgen Ekim Üstünel, Heidelberg
Anastasia Georgiadi, HMGU
Martina Guthoff, IDM
Christian Herder, DDZ
Stephan Herzig, HMGU
Susanna Hofmann, HMGU
Andrea Icks, DDZ
Natalie Krahmer, HMGU
Katharina Laubner, Freiburg
Haifa Maalmi, DDZ
Timo Müller, HMGU
Annette Peters, HMGU
Maria Rohm, HMGU
Sabrina Schlesinger, DDZ
Tim Julius Schulz, DIfE
Matthias Schulze, DIfE
Annette Schürmann, DIfE
Jochen Seufert, Freiburg
Bilal Sheikh, HMGU
Sabine Steffens, HMGU
Alexander Strom, DDZ
Alba Sulaj, Heidelberg
Julia Szendrödi, Heidelberg
Barbara Thorand, HMGU
Robert Wagner, DDZ
Rui Wang-Sattler, HMGU
Siegfried Ussar, HMGU
Eleftheria Zeggini, HMGU

Complications of diabetes impair quality of life and increase mortality. DZD researchers are developing evidence-based strategies to specifically prevent, treat or even reverse these complications.

The “Emerging Treatments of Diabetes Complications” Academy investigates the molecular causes of organ damage in diabetes and develops new therapeutic approaches. The aim is to detect complications at an early stage, treat them in a targeted manner or even reverse them. The focus is on personalized risk stratification, innovative lifestyle and drug interventions as well as new disease areas such as pulmonary fibrosis and cancer cachexia.

Key areas of research

  • Identification and risk stratification of people with regard to diabetes-related complications.
  • Development of lifestyle and pharmacological approaches to prevent and reverse these complications.
  • Identification and functional characterization of novel metabolic and organ-specific dysfunctions associated with long-term diabetes.

Identification of biomarkers and genetic risk factors

To achieve its goals, the Academy uses comprehensively characterized clinical and population-based cohorts, preclinical models and advanced technologies. These enable the identification of biomarkers and genetic risk factors for specific patient groups. On this basis, combinatorial peptide and RNA therapeutics as well as lifestyle interventions are being developed. These activities are linked to research in the other DZD academies.

Diabetes subtypes influence the course of the disease

DZD studies have shown that subtypes of patients with newly diagnosed type 2 diabetes (T2D) can be differentiated using an innovative algorithm. This method enables a more precise stratification of central pathophysiological processes and diabetes-related complications in the course of the disease. In addition, it has been shown that certain subtypes are associated with an increased risk of developing clinically relevant depressive symptoms. 

Furthermore, mechanistically stratified genetic risk scores have been developed for T2D. Based on data from over 2.5 million people, these scores showed correlations with complications such as cardiovascular disease and diabetic nephropathy. The results provide new approaches for personalized T2D treatment.

Validation of own peptide polyagonists

Researchers at the Academy are leading in the development of novel polyagonists for the treatment of T2D and its complications. They combined three agonists (GIP:GLP-1:glucagon) in one molecule that simultaneously activates three different receptors. The triple agonist was successfully tested in a clinical study in collaboration with Novo Nordisk. It improved blood glucose control and significantly reduced weight – with unprecedented metabolic efficacy and tolerability approaching that of GLP-1 receptor agonists.

Cancer cachexia – a long-term complication of diabetes

Cancer cachexia is now as common a cause of death in people with diabetes as cardiovascular disease. Following the identification of cancer cachexia as a potential long-term complication of diabetes in 2023 and the realization of the importance of muscle wasting under incretin therapy, Maria Rohm and Stephan Herzig received the DZG Innovation Fund for a cross-DZG research project on “Wasting Metabolism,” which was initiated by the DZD Academy.

Publications

Quarta C et al. GLP-1-mediated delivery of tesaglitazar improves obesity and glucose metabolism in male mice. Nat Metab (2022). https://doi.org/10.1038/s42255-022-00617-6

Schön M et al. Analysis of type 2 diabetes heterogeneity with a tree-like representation. Lancet Diabetes Endocrinol (2024). https://doi.org/10.1016/S2213-8587(23)00329-7

Suzuki K et al. Genetic drivers of heterogeneity in type 2 diabetes pathophysiology. Nature (2024). https://doi.org/10.1038/s41586-024-07019-6

von Rauchhaupt E et al. Glucose Load Following Prolonged Fasting Increases Oxidative Stress-Linked Response. Diabetes Care (2024). https://doi.org/10.2337/dc24-0209

Kaltenecker D et al. Functional liver genomics identifies hepatokines promoting wasting in cancer cachexia. Cell (2025). https://doi.org/10.1016/j.cell.2025.06.039