TIRZEPATIDE

Source: INDIANEXPRESS

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Context

• Tirzepatide, a groundbreaking medication by Eli Lilly and Company, is on the verge of transforming obesity treatment in India.
• Already approved for managing type 2 diabetes and obesity in the US and Europe, tirzepatide has shown promising results in clinical trials.
• The recent recommendation by an expert committee of India’s drug regulator signifies a potential approval for commercial availability in India soon.

Details

Tirzepatide

• Tirzepatide is a novel medication designed to improve glycemic control in adults with type 2 diabetes mellitus.
• It acts as a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist, making it unique among diabetes medications.

Mechanism of Action

• Tirzepatide combines the effects of two incretin hormones, GIP and GLP-1, which play significant roles in regulating glucose metabolism.
• GIP Agonism: GIP promotes insulin secretion from pancreatic beta cells and inhibits glucagon secretion from alpha cells in a glucose-dependent manner.
• GLP-1 Agonism: GLP-1 also stimulates insulin secretion and inhibits glucagon release. Additionally, it slows gastric emptying and promotes satiety, aiding in weight reduction.
• By targeting both receptors, tirzepatide enhances glucose-dependent insulin secretion, suppresses postprandial glucagon levels, and reduces appetite, leading to improved glycemic control and potential weight loss.

Clinical Trials

• Tirzepatide has undergone several clinical trials, demonstrating its efficacy in improving glycemic control and inducing weight loss in individuals with type 2 diabetes.
• SURPASS Program:
  • SURPASS-1: Tirzepatide as monotherapy showed significant reductions in HbA1c and body weight compared to placebo.
  • SURPASS-2: Compared to semaglutide, tirzepatide demonstrated superior glycemic control and greater weight loss.
  • SURPASS-3: When added to metformin, tirzepatide provided substantial HbA1c and weight reductions compared to insulin degludec.
  • SURPASS-4: Evaluated cardiovascular outcomes, showing favorable effects on HbA1c, body weight, and cardiovascular risk factors.

Dosage and Administration

• Tirzepatide is administered once weekly via subcutaneous injection.
• It is available in different dosages, typically starting at a lower dose and titrated upwards based on the patient's response and tolerability.

Comparison with Semaglutide

Both semaglutide and tirzepatide are effective for weight loss and diabetes management:

• Semaglutide: Targets GLP-1 receptors only.
• Tirzepatide: Targets both GLP-1 and GIP receptors, potentially offering enhanced effects.

Clinical trials have shown that tirzepatide can result in greater weight loss compared to semaglutide.

Obesity in India

Prevalence and Trends: 

• Obesity has become a significant public health concern in India, with recent data indicating that approximately one in four Indians is overweight.
• According to the National Family Health Survey (NFHS-5) conducted in 2019-21, the prevalence of obesity has risen from the previous survey period (2015-16).
• Specifically, obesity rates among men aged 15-49 increased from 19% to 23%, and among women in the same age group, it rose from 21% to 24%.

Age and Gender Correlation: 

• Obesity tends to increase with age for both men and women.
• Younger individuals (ages 15-19) show lower obesity rates compared to older individuals (ages 40-49).

Urban-Rural Divide: 

• Urban areas exhibit higher obesity rates compared to rural areas.
• About 30% of men in urban areas are overweight, compared to 19% in rural regions.
• Similarly, 41% of men aged 40-49 in urban areas are obese, versus 32% in rural areas.

Wealth and Obesity: 

• Obesity prevalence correlates with household wealth.
• As household wealth increases, the proportion of obese individuals also rises. For example, 10% of women in the lowest wealth quintile are obese, compared to 39% in the highest quintile.

State-wise Variations: 

• States such as Delhi and Tamil Nadu show higher obesity rates, with 38% and 37% of men being obese, respectively.
• Among women, Puducherry and Chandigarh have the highest obesity rates at 46% and 44%, respectively.

Initiatives, Policies, and Programs

• National Programme for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases and Stroke (NPCDCS):This program aims to tackle non-communicable diseases, including obesity, through health promotion, early diagnosis, and management. It focuses on lifestyle interventions, creating awareness, and improving healthcare facilities for early detection and treatment.
• Fit India Movement:Launched in 2019, this initiative encourages people to incorporate physical activity and sports into their daily lives. The movement includes various programs and campaigns to promote a healthy lifestyle and fitness among all age groups.
• Poshan Abhiyaan (National Nutrition Mission):This mission aims to reduce malnutrition and address the issues of undernutrition, anemia, and obesity. It promotes balanced nutrition and encourages healthy eating practices, particularly among children and women.
• Ayushman Bharat:Under this scheme, Health and Wellness Centers (HWCs) provide comprehensive primary healthcare services, including preventive measures and health promotion activities related to lifestyle diseases like obesity.
• School Health Program:Part of the Ayushman Bharat scheme, this program focuses on the health and well-being of school children. It includes periodic health check-ups, nutritional assessments, and promoting physical activities in schools.

Challenges

• Awareness and Education:Despite the various initiatives, there is a need for increased awareness and education about the health risks associated with obesity and the importance of maintaining a healthy lifestyle.
• Access to Healthcare:Ensuring access to healthcare facilities, particularly in rural areas, remains a challenge. Strengthening primary healthcare systems to manage and prevent obesity effectively is crucial.
• Policy Implementation:Effective implementation of policies and programs at the grassroots level is necessary to address the growing obesity epidemic. Continuous monitoring and evaluation of these programs can help in making necessary adjustments and improvements.
• Research and Data Collection:Ongoing research and data collection are essential to understand the changing trends in obesity and to develop targeted interventions. This includes studying the impact of various socio-economic factors on obesity prevalence.
• By addressing these challenges and continuing to promote healthy lifestyles through various initiatives, India can work towards reducing the obesity burden and improving overall public health.

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Sources:

INDIANEXPRESS

PRACTICE QUESTION Q: With reference to tirzepatide, consider the following statements: Tirzepatide is a dual GIP and GLP-1 receptor agonist. It is primarily used to manage type 2 diabetes. Tirzepatide is administered orally. Which of the statements given above is/are incorrect? (a) 1 and 2 only (b) 3 only (c) 1 and 3 only (d) 1, 2, and 3 Answer: (b)