Semaglutide vs Tirzepatide: Differences and Similarities

What is Semaglutide?

Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 сахарный диабет (T2D) and chronic weight management. It mimics the action of endogenous GLP-1, a hormone that regulates insulin secretion, glucagon suppression, and appetite. Semaglutide’s prolonged half-life (∼1 week) allows for once-weekly subcutaneous administration, making it a convenient option for long-term use.

How Does Semaglutide Work?

Semaglutide binds to GLP-1 receptors in the pancreas, brain, and gastrointestinal tract. Its mechanisms include:

1. Insulin Secretion: Glucose-dependent stimulation of insulin release.
2. Glucagon Suppression: Reduces hepatic glucose production.
3. Gastric Emptying: Slows digestion, promoting satiety.
4. Appetite Regulation: Acts on hypothalamic receptors to reduce hunger.

Semaglutide for Weight Loss

In the STEP clinical trials, semaglutide demonstrated significant weight loss efficacy. Participants receiving 2.4 mg weekly lost ~15% of body weight over 68 недели, в сравнении с 2.4% with placebo. Weight loss is attributed to reduced caloric intake via appetite suppression and delayed gastric emptying.

Semaglutide Mechanism of Action

As a selective GLP-1 analog, semaglutide enhances insulin sensitivity and promotes beta-cell proliferation. Its structure includes a fatty acid side chain, enabling albumin binding for extended activity.

Semaglutide Weight Loss Dosage Chart

Semaglutide Side Effects

Common: Nausea (44%), diarrhea (30%), vomiting (24%).
Rare: Acute pancreatitis, gallbladder disease, diabetic retinopathy.
Black Box Warning: Thyroid C-cell tumors in rodents; contraindicated in personal/family history of medullary thyroid carcinoma (MTC).

What is Tirzepatide?

Tirzepatide is a first-in-class dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist. It targets both receptors, enhancing insulin secretion and appetite regulation beyond single GLP-1 agonists. Approved for T2D in 2022, it shows superior efficacy in weight loss compared to semaglutide.

Tirzepatide Mechanism of Action

Tirzepatide activates GLP-1 and GIP receptors:

1. GIP Receptor: Enhances insulin secretion and adipose tissue glucose uptake.
2. GLP-1 Receptor: Mirrors semaglutide’s effects (appetite, insulin, glucagon).
   Synergistic action improves glycemic control and weight loss.

Tirzepatide for Weight Loss

In SURMOUNT-1, participants lost up to 22.5% of body weight (15 mg dose) над 72 недели. Dual agonism may amplify satiety signals and lipolysis, outperforming single GLP-1 agonists.

Tirzepatide Side Effects

Common: Nausea (33%), diarrhea (23%), запор (12%).
Rare: Hypoglycemia (when combined with insulin/sulfonylureas), pancreatitis.
Warning: Similar thyroid tumor risk as semaglutide.

Semaglutide vs Tirzepatide: Differences

1. Mechanism:
   • Semaglutide: Single GLP-1 agonist.
   • Tirzepatide: Dual GIP/GLP-1 agonist.
2. Efficacy:
   • Потеря веса: Tirzepatide (15–22.5%) > Semaglutide (10–15%).
   • HbA1c Reduction: Tirzepatide (-2.3%) > Semaglutide (-1.8%).
3. Дозировка:
   • Semaglutide: Максимум 2.4 mg/week.
   • Tirzepatide: Максимум 15 mg/week.
4. Molecular Structure:
   • Semaglutide: Modified GLP-1 with fatty acid side chain.
   • Tirzepatide: Synthetic 39-amino acid peptide with C18 diacid.

Semaglutide vs Tirzepatide: Similarities

1. Administration: Both are weekly subcutaneous injections.
2. Appetite Suppression: Central action on brain receptors.
3. Побочные эффекты: GI disturbances dominate; thyroid tumor warnings.
4. Indications: T2D and obesity (off-label for tirzepatide pending approval).

Clinical Use and Precautions

Target Populations:

• Semaglutide: Patients with BMI ≥27 (comorbidities) or ≥30. Suitable for those needing moderate weight loss.
• Tirzepatide: Patients with BMI ≥30 or inadequate response to GLP-1 agonists.

Меры предосторожности:

• Avoid in pregnancy (Category C).
• Monitor for pancreatitis, gallbladder disease, and renal impairment.
• Contraindicated in personal/family history of MTC or Multiple Endocrine Neoplasia syndrome.

Ссылки

1. Davies, М., и др.. (2021). Semaglutide 2.4 mg Once a Week in Adults with Overweight or Obesity. NEJM, 384(11), 989–1002.
2. Frías, Дж. P., и др.. (2021). Tirzepatide versus Semaglutide Once Weekly in Type 2 Диабет. NEJM, 385(6), 503–515.
3. FDA (2021). Wegovy (semaglutide) Prescribing Information. Retrieved fromFDA.gov.
4. Lilly (2022). Mounjaro (tirzepatide) Prescribing Information. Retrieved fromMounjaro.com.
5. Jastreboff, А. М., и др.. (2022). Tirzepatide Once Weekly for the Treatment of Obesity. NEJM, 387(3), 205–216.