Semaglutide and Tirzepatide

Year/Period

Event/Discovery

1906

Concept of incretins (gut hormones that affect insulin) first proposed.

1921

Insulin discovered; incretin research largely ignored thereafter.

1960s

Scientists find that oral glucose causes more insulin release than IV glucose, reviving interest in gut hormones.

1986

GLP-1 (Glucagon-Like Peptide-1), a key incretin, discovered.

1990s

GLP-1 tested and found to increase insulin and lower blood sugar, but unstable in the body.

2000s

Novo Nordisk begins work on GLP-1-based drugs for diabetes and obesity.

2010

Liraglutide (first GLP-1-based daily injection) introduced; caused nausea in many users.

Mid-2010s

Semaglutide, a weekly GLP-1 injection, developed to improve effectiveness and reduce side effects.

2021

Semaglutide approved in the US for obesity treatment after showing 15% weight loss.

2022–2023

Studies confirm semaglutide's benefits for heart, liver, and overall mortality reduction.

2023–2024

Tirzepatide, a dual-action drug (GLP-1 + GIP), found to result in 20% weight loss and approved for sleep apnoea.

2024–2025

Clinical trials begin for newer drugs:

1. GLP-1 (Glucagon-Like Peptide-1): 
   1. Made in the small intestine.
   2. Main functions:
      1. Stimulates insulin release from the pancreas (helps lower blood sugar).
      2. Suppresses glucagon (a hormone that increases blood sugar).
      3. Slows stomach emptying, leading to slower glucose absorption.
      4. Reduces appetite by signaling the brain to feel full.
   3. Used in: Diabetes and obesity treatment (e.g., semaglutide, liraglutide).

GIP (Gastric Inhibitory Polypeptide or Glucose-Dependent Insulinotropic Polypeptide)

1. Made in the small intestine.
2. Main functions:
   1. Enhances insulin secretion in response to food.
   2. May help regulate fat metabolism.
   3. When combined with GLP-1 action (as in Tirzepatide), it enhances weight loss and glucose control.
3. Research ongoing to fully understand its role in appetite and metabolism.

Component

Type

Function

Role in Drugs

GLP-1

Natural incretin hormone

 Boosts insulin, lowers glucagon- Slows stomach emptying- Reduces appetite

Mimicked by semaglutide and tirzepatide

GIP

Natural incretin hormone

 Increases insulin secretion- may improve fat metabolism

Also mimicked by tirzepatide

Semaglutide

Synthetic drug (GLP-1 receptor agonist)

Acts like GLP-1 only- Used to treat type-2 diabetes and obesity

Mimics only GLP-1

Tirzepatide

Synthetic dual agonist

 Mimics both GLP-1 and GIP- More effective in weight loss and sugar control

Mimics GLP-1 + GIP

Domain

Significance

1. Medical

Major non-surgical breakthrough in treating obesity and type-2 diabetes.

Offers 15–20% body weight loss, comparable to bariatric surgery.

2. Cardiovascular

Reduces heart attack and stroke risk by 20%.

Lowers heart failure risk by 69%. -

Decreases mortality by 19% from any cause.

3. Liver Health

Clears fat from liver in 63% of patients.

Improves liver fibrosis (tissue hardening) in 37% of cases.

4. Neurological

Early research suggests potential to reduce risk of Alzheimer’s and dementia, marking a neurological benefit.

5. Psychological

Suppresses appetite and cravings, especially for sugar and alcohol.

May support mental well-being through better eating behaviour.

6. Endocrine Function

Increases insulin secretion.

Decreases glucagon levels, reducing blood sugar spikes.

Stabilizes blood sugar via incretin mimicry.

7. Digestive Regulation

Slows gastric emptying, preventing post-meal sugar spikes and helping with satiety.

8. Healthcare Systems

Could reduce reliance on surgery and chronic disease management costs.

Allows preventive care for multiple conditions with a single drug.

9. Public Health Impact

Shows promise for mass-scale lifestyle disease control. Encourages integrated metabolic health solutions.

Challenges

Way Forward

1. High cost of GLP-1 and GIP-based drugs, limiting access in low-income populations.

Encourage generic versions and price controls for equitable access.

2. Long-term safety and side effects are still being studied.

Continue post-marketing surveillance and long-term studies.

3. Overdependence on medication for weight loss may ignore root causes like lifestyle.

Integrate with diet, counselling, and physical activity programs.

4. Limited public awareness and healthcare provider knowledge in rural areas.

Invest in medical education and awareness campaigns.

5. Risk of misuse or overuse for cosmetic purposes rather than health needs.

Strict regulatory guidelines and prescription protocols needed.

6. Current drugs are injectable, posing inconvenience.

Fast-track development and approval of oral formulations.

Ensure IAS Mains Question:

Q. The emergence of GLP-1 and GIP-based therapies like Semaglutide and Tirzepatide marks a breakthrough in the management of lifestyle-related diseases. Discuss the medical and public health significance of these drugs. What challenges do they pose in the Indian context, and how can they be effectively addressed? (250 words)

Ensure IAS Prelim Question:

Q. Consider the following statements with respect to incretin-based drugs:

1. Semaglutide is a GLP-1 receptor agonist approved for obesity treatment in 2021, resulting in approximately 15% weight loss.
2. Tirzepatide mimics both GLP-1 and GIP hormones, achieving up to 20% weight loss in clinical trials.
3. Incretin hormones were first discovered in the 1960s, with GLP-1 identified in 1986.

How many of the above statements are correct?

(A) Only one
(B) Only two
(C) All three
(D) None

Ans: B
Explanation:

Statement 1 is correct: Semaglutide, a GLP-1 receptor agonist, was approved for obesity in 2021 and results in 15% weight loss.

Statement 2 is correct: Tirzepatide, a dual GLP-1 and GIP agonist, achieves 20% weight loss.

Statement 3 is incorrect: The incretin concept was proposed in 1906, not the 1960s, though interest was revived in the 1960s, and GLP-1 was identified in 1986.