On 10 September, at the European Association for the Study of Diabetes (EASD) 60th Annual Meeting 2024, Eli Lilly and Co announced the most recent trial results for mazdutide, its dual glucagon-like peptide-1 receptor (GLP-1R)/glucagon receptor (GCGR) agonist. According to GlobalData, targeting glucagon receptor agonism might be the next trend in obesity treatment, to tackle energy expenditure.
Eli Lilly has been co-dominating the obesity market with Novo Nordisk with the entrance of Mounjaro/Zepbound (tirzepatide) in the space. The company has no intention of giving up its power in this market anytime soon, and it has in fact a few drugs in clinical development that may assure its long-lasting domination into the space. Companies seem to be investing into dual agonists targeting the GLP-1 and the glucagon receptors, and Eli Lilly is of course developing its own candidate for this drug class.
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Today in Madrid, Eli Lilly announced the Phase I trial (NCT05623839) results of mazdutide regarding changes in body weight, central adiposity, and fasting metabolic markers.
Mazdutide caused a 19%–21% bodyweight reduction in patients after 20 weeks of treatment. Central adiposity, measured by waist circumference, decreased by 12%–17% in mazdutide-treated patients versus 0.7% in the placebo group.
Lipid profiles of drug-treated patients improved, with a consistent decrease in cholesterol, low-density lipoprotein (LDL), very low-density lipoprotein (VLDL), high-density lipoprotein (HDL), and triglycerides.
Mazdutide also increased hepatic fatty acids oxidation via GCG receptor signalling and decreased HbA1c levels by 3.7mmol/mol to 4.9mmol/mol and fasting glucose by 10.34% on average, improving glycemic control. In some cases, mazdutide also decreased insulin markers.
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By GlobalDataKey opinion leaders (KOLs) interviewed by GlobalData mentioned that the introduction of GCG receptor agonism into the space looks very promising. In fact, at EASD 2024, glucagon receptor targeting is a hot topic. When referring to dual and triple agonists, a European KOL said: “Glucagon opens the possibility to have some effect on energy expenditure that, at the moment, we do not have with the GLP-1 receptor agonist or also with the GIP receptor agonism. Of course, the effect of glucagon needs to be evaluated. Because, you know, also, you can have some problem with heart rate. So we need to wait for the results. But the introduction of glucagon agonists is a very interesting additional tool. I can imagine the use of these drugs in patients with a very low energy expenditure, in which the control of eating intake is less important, is less relevant. People that are already restraining a lot, but they have very low energy expenditure. So, there is space for the drugs.”
In conclusion, mazdutide results on cardiovascular risk biomarkers are promising, showing that this dual GLP-1R/GCGR agonist does not negatively impact the cardiovascular system, but on the contrary, it improves it. Experts are enthusiastic about targeting GCG receptors as this type of drug is thought to convey additional benefits for obesity patients, mainly relating to increased energy expenditure.
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