Summary :
- The Food and Drug Administration (FDA) has approved a novel first-in-class drug to treat type 2 diabetes. The drug is called tirzepatide.
- It has a dual effect, lowering blood sugar and supporting weight loss better than currently available drugs for this condition.
- The most common side effects are nausea, diarrhea, and vomiting, which appear to lessen with time. There were also a few reports of severe low blood sugar in clinical trials.
- Eli Lilly has won another another battle with diabetes. The US Food and Drug Administration granted tirzepatide, a once-weekly dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, Priority Review approval.
About Tirzepatide
Tirzepatide Structure
- Tirzepatide activates the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors, which both play a role in blood sugar control, and is administered via injection once-weekly.
- Doses can be adjusted to meet individual patients’ blood sugar goals while 3 doses (5 mg, 10 mg, and 15 mg) were assessed in the 5 clinical trials supporting the approval.
Mechanism of Action
Glucagon-like peptide-1 (GLP-1) receptors (GLP-1R) are expressed throughout the body, including pancreatic beta-cells and the gastrointestinal tract. It is importantly implicated in the pathophysiology of type II diabetes mellitus as GLP-1R signalling is involved in glucose control by enhancing glucose-stimulated insulin secretion, delaying gastric transit, decreasing plasma glucagon levels, and reducing body weight by activating anorexigenic pathways in the brain. Both glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 are peptide hormones involved in glucose homeostasis: they promote glucose-stimulated insulin secretion from the pancreatic beta-cells. However, GIP is the main incretin hormone that exerts insulinotropic effects in response to food intake.
Tirzepatide MOA
The mechanism of action of tirzepatide has not been fully elucidated; however, glycemic and weight control effects of this drug are understood to arise from its dual agonism at GIP and GLP-1R. Studies demonstrated that co-administration of GIP and a GLP-1R agonist more significantly increased insulin response and suppressed glucagon secretion compared to separate administration of either hormone alone.3 Tirzepatide binds to GIP and GLP-1R with high affinity. In vitro, tirzepatide has a comparable GIP receptor binding affinity to native GIP and five times lower GLP-1R affinity than that of native GLP-1. Tirzepatide potently activates the GLP-1R signalling pathway to stimulate glucose-dependent insulin secretion through activity at either the GIP receptor (GIPR) or the GLP-1R. However, the role of GIPR agonism in the drug’s mechanism of action requires further investigation, as evidence of GIPR agonism on glycemic and weight control in preclinical and clinical studies are conflicting.
- Protein binding :Tirzepatide binds to Albumin
- Half-life :The half-life is approximately five days.
T2D is the most common form of the disease and currently affects over 30 million Americans. “Today’s FDA approval underscores our commitment to the discovery and development of new treatment pathways, and we are thrilled to bring this new and innovative treatment option to people living with T2D,” said Mike Mason, president, Lilly Diabetes, in a statement.
T2D is the most common form of the disease and currently affects over 30 million Americans. “Today’s FDA approval underscores our commitment to the discovery and development of new treatment pathways, and we are thrilled to bring this new and innovative treatment option to people living with T2D,” said Mike Mason, president, Lilly Diabetes, in a statement.
Tirzepatide activates the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors, which both play a role in blood sugar control, and is administered via injection once-weekly. Doses can be adjusted to meet individual patients’ blood sugar goals while 3 doses (5 mg, 10 mg, and 15 mg) were assessed in the 5 clinical trials supporting the approval.
Tirzepatide’s efficacy was compared with a placebo, the GLP-1 receptor agonist semaglutide, and 2 long-acting insulin analogues. Those randomized to 15 mg of the study treatment as a standalone therapy exhibited a 1.6% lower glycated hemoglobin (A1C) on average compared with those who received a placebo. When compared with those who received a placebo plus a long-acting insulin, A1C decreased by 1.5% on average among those taking tirzepatide.
Common adverse effects associated with tirzepatide include nausea, vomiting, diarrhea, and decreased appetite, among others. As the treatment was shown to cause thyroid C-cell tumors in rats, its indication precludes treatment for patients with a family history of medullary thyroid cancer or those with Multiple Endocrine Neoplasia syndrome type 2.
Study participants had an average body mass index of 32 to 34 kg/m2, while those randomized to 15 mg tirzepatide alone saw an average weight loss of 15 pounds more than placebo. When taken with insulin, those taking tirzepatide saw an average loss of 23 pounds more than those on placebo and insulin, while patients receiving insulin without tirzepatide tended to gain weight throughout the study period.
In addition, average weight loss with 15 mg of tirzepatide “was 12 pounds more than semaglutide, 29 pounds more than insulin degludec and 27 pounds more than insulin glargine.”
