Retatrutide vs tirzepatide vs semaglutide, what are the differences between them?
Obesity has become a global epidemic, and the incidence rate of obesity continues to soar in countries around the world. According to the World Health Organization (WHO), 13% of adults worldwide suffer from obesity. More importantly, obesity will further cause metabolic syndrome and various complications, such as type 2 diabetes, hypertension, nonalcoholic steatohepatitis (NASH), cardiovascular disease and cancer.
In June 2021, the FDA approved the marketing of Semaglutide, a weight loss drug developed by Novo Nordisk, under the brand name Wegovy. Due to its excellent weight loss effect, good safety, and the influence of celebrities such as Musk, semaglutide has become popular all over the world, even leading to the phenomenon of difficulty in finding a drug. According to the 2022 financial report released by Novo Nordisk, the sales of semaglutide in 2022 reached a staggering $12 billion.
Tirzepatide and Retatrutide, which are also about to be launched for weight loss? However, what are the differences between them?
Semaglutide: GLP-1 receptor agonist, pioneering the world of miracle drugs
What is GLP-1 receptor?
GLP-1 is an incretin secreted by L cells in the intestinal system, which affects insulin secretion under various complex effects, thereby affecting blood glucose and digestion, producing a series of effects. Weight loss is just one of them, and its indications are extending to liver disease and even Alzheimer’s disease. Its full name is Glucagon like peptide-1 receptor agonists, GLP-1 RA, which stands for GLP-1 glucagon like peptide-1 receptor.
There are 184 GLP-1 target pipelines under development worldwide, including 97, 60, 21, and 6 drugs for single target, dual target, triple target, and multi-target, respectively. The so-called dual targets and multiple targets refer to drugs with multiple target mechanisms, such as GLP-1/GIP dual targets and GLP/GIP/GCGR triple targets.
Semaglutide is a GLP-1 receptor agonist developed by Novo Nordisk, a leader in the field of diabetes treatment. This drug can increase glucose metabolism by stimulating pancreatic beta cells to secrete insulin. It inhibit pancreatic alpha cells from secreting glucagon, thereby reducing fasting and postprandial blood glucose. In addition, it can also reduce food intake by lowering appetite and slowing down stomach digestion, ultimately reducing body fat, which is beneficial for weight loss.
Tirzepatide: GLP-1/GIP dual target agonist
GIP and GLP-1 are both hormones secreted by the intestine. They both constitute the majority of the gut stimulating effect. They promoting insulin secretion and playing an indispensable role in controlling sugar and weight.
The MOA of GIP and GLP-1 are not completely identical, but complement each other. Therefore, GLP-1/GIP dual target agonists can effectively exert the synergistic effect of the two receptors in reducing blood sugar and controlling body weight.
The weight loss drug developed by Lily, tirzepatide, mimics the effect of natural GIP on GIP receptors. It shows a bias towards cAMP production rather than β – inhibin recruitment on GLP-1 receptors. Compared with GLP-1, tizepaide has a weaker ability to drive GLP-1 receptor internalization. This drug combines synthetic mimetics of GLP-1 and GIP hormones. Those are naturally released from the intestines after consumption, making people feel full.
Retatrutide: a peptide drug with three targets GLP-1R/GCGR/GIPR
Retatrutide (LY3437943) is a peptide drug developed by Eli Lilly based on the GIP peptide sequence, targeting GLP-1R/GCGR/GIPR. Its average half-life in humans is up to 6 days, and its half-life in mice is 21 hours (0.47mg/kg).
Retatrutide is a single peptide modified from the GIP peptide backbone. It containing 39 amino acids, and can achieve triple agonist activity in GCGR, GIPR, and GLP-1R. The peptide backbone sequence contains three non coding amino acid residues at positions 2, 20, and 13. Among them, Aib2 (α – aminoisobutyric acid) helps to improve stability against degradation by dipeptidyl peptidase-4 (DPP4); Aib20 helps optimize GIP activity, pharmacokinetic properties, and exploitability; α MeL13 (α – methyl-L-leucine) helps optimize glucagon (GCG) and GIP activity. The skeleton is coupled to a C20 fatty acid moiety through a linker located at the 17th lysine residue, which extends the half-life through albumin binding and provides the desired pharmacological properties.
What are the difference in weight loss effects among retatrutide VS tirzepatide VS semaglutide ?
Semaglutide has reduced weight by at least 20% in one-third of obese individuals.
More than half of obese individuals have lost at least 20% of their weight with Tirzepatide
At 48 weeks of treatment, participants who received weekly injections of 12mg retatrutide experienced an average weight loss of 24.2%. This surpassing the previous record for weight loss achieved by Eli Lilly’s own Tirzepatide.
