Tirzepatide is a novel dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist that has gained significant attention in the medical field for its metabolic benefits. This synthetic polypeptide was approved by the US Food and Drug Administration (FDA) in May 2022 for treating type 2 diabetes mellitus (T2DM).

Tirzepatide acts by activating both GIP and GLP-1 hormone receptors, which helps control appetite and blood sugar levels. This dual-action mechanism provides enhanced effectiveness compared to medications that target only one receptor pathway.

Semaglutide dosages range from 0.25mg per week to 1mg per week. This peptide is typically injected subcutaneously (in the abdominal area), but an oral option also exists. It is important to remember that Semaglutide has a long half-life, which means that starting off with too much can lead to a very rough week for you. Unless instructed differently by a physician, start off at the minimum dosage.

The journey of semaglutide began in the 1970s with groundbreaking research on incretin hormones by scientists Jens Juul Holst, Joel Habener, and Svetlana Mojsov. Holst discovered that gut hormones affected insulin secretion, while Habener and Mojsov used emerging recombinant DNA technology to identify and characterize GLP-1 (glucagon-like peptide-1). Their research revealed that GLP-1 stimulated insulin secretion but had an extremely short half-life of only 1-2 minutes in the bloodstream, limiting its therapeutic potential. These discoveries established the scientific foundation for developing GLP-1-based medications that would eventually transform diabetes and obesity treatment.

Building on this foundation, scientists at Novo Nordisk, led by Lotte Bjerre Knudsen, began developing modified versions of GLP-1 with extended half-lives. They first created liraglutide in 1998, then pursued the development of semaglutide as a once-weekly alternative. Semaglutide's design incorporated several critical modifications: an amino acid substitution to prevent enzymatic degradation and a C18 fatty diacid attachment that enhanced albumin binding and reduced renal clearance, extending its half-life to approximately seven days. After extensive testing of roughly 4,000 molecular variations, researchers finalized semaglutide's structure, achieving the optimal balance between potency and extended duration.

Clinical trials for semaglutide began with a Phase II study in 2008, followed by the comprehensive SUSTAIN clinical trial program across multiple countries. The FDA approved injectable semaglutide (Ozempic) for type 2 diabetes in December 2017 based on seven clinical trials involving over 4,000 patients. Further research demonstrated semaglutide's effectiveness for weight management, leading to the approval of a higher-dose formulation (Wegovy) in June 2021—the first new drug approved for chronic weight management since 2014. Subsequent trials showed cardiovascular benefits, resulting in additional FDA approval for reducing cardiovascular risks. Novo Nordisk also developed an oral formulation (Rybelsus), expanding treatment options and making semaglutide one of the most significant therapeutic advances in metabolic health in recent decades.

‍

Tirzepatide offers multiple significant benefits:

1. Improved Glycemic Control: Clinical data demonstrates that tirzepatide is superior to placebo in improving hemoglobin A1c (HbA1c) levels, with the SURPASS-5 clinical trial showing a -2.11% reduction at 5 mg per week dosing.
2. Weight Management: Patients on Zepbound (tirzepatide) showed remarkable weight loss in clinical trials - 16.1 kg (35.5 lb) on average with 5 mg weekly, 22.2 kg (48.9 lb) with 10 mg weekly, and 23.6 kg (52.0 lb) with 15 mg weekly over 72 weeks. At week 72, the majority (89% to 91%) of participants receiving 10-mg or 15-mg doses achieved at least 5% weight reduction, which is considered the threshold for clinically meaningful effect.
3. Cardiovascular Benefits: Benefits were observed with respect to changes in waist circumference, systolic and diastolic blood pressure, fasting insulin level, and lipid levels.
4. Metabolic Improvements: At week 72, most (95.3%) of the participants with prediabetes at baseline in the tirzepatide groups had reverted to normoglycemia, compared with 61.9% of participants in the placebo group.

‍

The most common tirzepatide side effects (affecting 5% or more patients) include abdominal pain, burping, constipation, diarrhea, dyspepsia, fatigue, gastroesophageal reflux disease, hair loss, hypersensitivity reactions, injection site reactions, nausea, and vomiting.

More serious potential side effects include:

• Risk of thyroid C-cell tumors
• Pancreatitis
• Gallbladder problems
• Acute kidney injury due to dehydration
• Hypoglycemia (especially when used with insulin or sulfonylureas)

Tirzepatide is a novel dual GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist that has gained significant attention in the medical field for its metabolic benefits. This synthetic polypeptide was approved by the US Food and Drug Administration (FDA) in May 2022 for treating type 2 diabetes mellitus (T2DM).

Tirzepatide acts by activating both GIP and GLP-1 hormone receptors, which helps control appetite and blood sugar levels. This dual-action mechanism provides enhanced effectiveness compared to medications that target only one receptor pathway.