GLP-3: A New Frontier in Obesity Treatments
Recently, “GLP-3” has emerged as a term creating buzz within the weight loss community, with some suggesting it could elevate obesity medications beyond their current capabilities. GLP-1 (glucagon-like peptide-1) drugs are already well-known for mimicking hormones in our bodies that help control blood sugar and hunger.
However, GLP-3 refers to an innovative triple agonist drug that targets three different hormones: GLP-1, GIP (glucose-dependent insulinotropic polypeptide), and the glucagon receptor. Eli Lilly’s letaltortide is noted as the most developed of these drugs, according to various clinical trials.
The New England Journal of Medicine published findings from the 2023 phase 2 letaltortide trial, highlighting “significant weight loss” after 48 weeks of treatment. Participants receiving a weekly 12 mg injection lost an average of 24.2% of their body weight and continued to shed pounds even after the study concluded.
Reported side effects appear similar to those associated with GLP-1 medications, mainly involving gastrointestinal issues such as nausea, vomiting, and diarrhea, with some participants experiencing increased heart rates depending on dosage.
What Sets GLP-3 Apart?
Unlike GLP-1, which mimics a single hormone, letaltortide affects three hormones from the body. The hormones GIP and GLP-1 instruct the pancreas to release insulin post-meal, helping slow digestion and making individuals feel fuller. Additionally, the glucagon hormone boosts metabolism and assists the body in breaking down fat cells for energy, while regulating liver sugar production to prevent spikes in blood sugar.
This additional metabolic boost is thought to enhance the effects of GIP and GLP-1, likely leading to more significant weight loss. In December, Eli Lilly shared insights from its Phase 3 trial, known as TRIUMPH-4, focusing on letaltortide’s weight loss outcomes and other health benefits.
Participants battling obesity and knee arthritis who received the 12 mg dose lost an average of 71.8 pounds (28.7%) over 68 weeks. Furthermore, pain levels—measured using the Western Ontario and McMaster Universities Osteoarthritis Index—dropped by 75.8%, along with noted improvements in comfort and physical function.
Interestingly, over one in eight study participants reported their knee pain as “completely gone” by the trial’s end. Seven additional Phase 3 trials for letaltortide are slated for completion in 2026, with potential FDA approval anticipated by 2027.
“The results from TRIUMPH-4 are promising, as they underscore letaltortide’s substantial impact on weight, pain, and physical function,” said Dr. Kenneth Castor from Lilly Cardiometabolic Health. The ongoing research suggests letaltortide could offer significant benefits to patients with weight management needs and accompanying conditions like knee osteoarthritis.
Experts, including GoodRx, propose that while data on this drug remains limited, it may also address other issues such as type 2 diabetes, kidney disease, cardiovascular risks, and metabolic disorders.
Medical analysts note that Lilly’s Zepbound and Mounjaro target two pathways—GLP-1 and GIP—that already facilitate weight loss, diminish hunger, and enhance insulin function. The introduction of a third receptor agonist in letaltortide aims to boost satiety even further.
Side effects of GLP-3 drugs mainly include gastrointestinal symptoms, though there are rare reports of more serious issues like pancreatitis and gallstones. Overall, the developments surrounding GLP-3 injections are certainly something to watch in the realm of obesity treatments.
