Prof. Dr. Sebastian Schmid (University of Lübeck, Germany) spoke at the DGIM Congress in the session "Drug therapy approaches - today and in the future", where obesity was a central topic.
By way of introduction, the endocrinologist stated: "Drug therapy for obesity is currently still very limited. There are few approved substances. In addition, the few approved substances are not reimbursable in the German social security. Under current legislation, obesity is not defined as a disease. "This is a problem that we must continue to address politically," argued Prof. Dr. Schmid.
What does a drug-based obesity therapy accomplish? Regulatory studies for liraglutide at a 3.0mg formula for obesity show a weight loss of about 9% within one year compared with placebo-treated patients. This is true for patients with prediabetes as well as those with a normoglycemic metabolic status. However, it is not only a question of absolute weight loss, but also of weight categories. Here, two-thirds of patients have achieved more than 5% weight loss under therapy. About one-third show a weight loss of more than 10% of the initial weight.
The so-called super responders, i.e. the 15% who respond particularly well, achieve more than 15% weight loss. Conversely, this means that one third does not lose more than 5%. In practice, the physician therefore looks at the course of treatment over three months and if the weight loss remains below 5%, the therapy should be stopped.
Liraglutide as an obesity therapy is currently approved for adults. But initial studies show that the therapy can also be used safely in adolescents. The spectrum of effects and side effects does not differ from that of adults.
Drug therapies in the context of the totality of treatment options
By comparison, the lowest effect strength is seen with conservative therapy. Pharmacotherapy is slightly better, and bariatric surgery clearly shows the highest effect level. In the eyes of the session’s speaker, however, this means that there is a very large space for innovation between the options, where further pharmacological therapies may have a greater space for contribution.
A wide variety of approaches are currently in the research phase. For example, mechanisms and signaling pathways that are addressed in the peripheral nervous system, as well as central nervous targets. Currently under discussion are even more effective GLP1 receptor agonists that can also be combined with other incretin metabolic hormones, so-called dual or triple agonists. One can also focus on other gastrointestinal peptides, such as peptide tyrosine tyrosine or PYY.
For the compound semaglutide, established in type-2 diabetes, pivotal studies for obesity therapy at a dose of 2.4 mg once a week, show a significant weight reduction over one year of 16% from baseline weight. A cardiovascular endpoint study involving 17,000 patients worldwide is underway. Prof. Schmid considers the results relevant in light of the eventual recognition of obesity as a disease.
Other future options include tirzepatide: the peptide hormone can bind to two receptors and is already relatively far along in the approval process. In early clinical studies, no plateau was reached at the dosage of 15mg once a week, i.e. weight loss obviously continued to progress. Very clear effects are to be expected here. It will be interesting to see how drug-based obesity therapy continues to develop.
Source:
DGIM Congress 2021; Prof. Dr. Sebastian Schmid: Drug therapy approaches - today and in the future.