Somatostatin Receptor Inhibitors for Sustaining Muscle and Bone Mass Following Pharmacologically Induced Weight Loss

Obesity affects 1 in 6 adults in Europe, driving demand for therapy.

Agonists of the Glucagon Like Peptide 1 Receptor (GLP1RAs) such as semaglutide (Novo Nordisk) and tirzepatide (Eli Lilly) have led to substantial weight loss in millions of patients. However, a large fraction of lost weight is attributed to loss of lean mass: muscle and bone. A reduction in lean mass increases the risk for sarcopenia and osteoporosis loss of muscle and bone.

Our analysis of 748,667 patients using GLP1RAs has shown that most are women, over the age of 50: a population already at risk for muscle and bone loss.

Sarcopenia and osteoporosis cause pain, fatigue, limit the ability of patients to perform daily activities, and increase their risk for fractures.

With millions of GLP1RA users and an annual direct cost of 5000USD/osteoporosis patient, loss of lean mass can cost billions to health care systems.Growth Hormone (GH) is the natural signal in adults for sustaining lean mass. Results from our ERC project identified pathways that may sustain GH signaling during and after weight loss.

We propose to develop novel molecules that will lead to an increase in natural GH secretion.

We will test the efficacy and safety of a library molecules we designed for their ability to maintain lean mass during GLP1RA-induced weight loss.

The results will secure the intellectual property surrounding the novel molecules and their use.By addressing the underlying causes of muscle and bone loss, we aim to develop a comprehensive solution to the obesity crisis.

Our innovative biochemical approach targets the aging population struggling with obesity and has the potential to prevent disease in millions of patients and alleviate a significant burden from healthcare systems.