The GLP-1 analogues tirzepatide in Mounjaro and semaglutide in Wegovy and Ozempic are available from LondonSwissMedical. Dr Philip Kelly describes how they benefit patients, help weight loss, diabetes and glucose control, lipids and overall cardiovascular health. #CardiovascularDisease #Diabetes #WeightManagement

Wegovy and Ozempic are the brand names for semaglutide, and Mounjaro is the brand name for tirzepatide.

Semaglutide is a GLP-1 (glucagon like peptide 1) agonist and tirzepatide is a dual-agnoist for GLP-1 and GIP (gastric inhibitory polypeptide, also known as glucose dependant insulinotropic polypeptide).

**What do GLP-1 agonists do?**

GLP-1 (glucagon-like peptide-1) agonists are a class of medications primarily used to treat type 2 diabetes and, more recently, obesity. They mimic the action of the natural hormone GLP-1, which is involved in the regulation of blood sugar levels and appetite. Here’s how they work:

  1. **Stimulate Insulin Secretion**: GLP-1 agonists enhance the secretion of insulin from the pancreas in response to meals, this helps to lower blood glucose levels and store protein, dietary fats, minerals and micronutrients effectively.

  2. **Inhibit Glucagon Release**: They reduce the release of glucagon; glucogon is a hormone that raises blood sugar levels by promoting the release of glucose from the liver. In health, glucagon and insulin acts in balance with each other.

  3. **Slow Gastric Emptying**: Slowing stomach emptying helps to reduce the rate glucose enters the bloodstream, leading to better post-meal blood glucose control.

  4. **Promote Satiety**: GLP-1 agonists adjust the communication from the gut to the brain to promote a feeling of fullness, this can help with weight loss.

Overall, these effects help to improve blood glucose control and reduce body weight in individuals with type 2 diabetes or obesity.

**How is a dual agonists, like tirzepatide in Mounjaro, different?**

Tirzepatide and semaglutide both help manage type 2 diabetes and promote weight loss, but they have distinct mechanisms of action and effects due to their different molecular targets:

1. **Dual Receptor Agonism**: - **Tirzepatide**: Acts as a dual agonist for both the GLP-1 receptor and the GIP receptor. This dual agonism may provide additional benefits in glucose control and weight loss by leveraging the complementary actions of both incretin hormones. - **Semaglutide**: Acts solely as a GLP-1 receptor agonist.

2. **Glucose Control**: - Both medications lower blood glucose, but the dual action of tirzepatide on GLP-1 and GIP receptors may offer superior glucose control for some patients.

3. **Weight Loss**: - Clinical studies have suggested that tirzepatide may lead to greater weight loss than semaglutide; this is likely due to its dual mechanism which enhances satiety and reduces appetite more effectively.

4. **Insulin Sensitivity**: - Tirzepatide has been shown to improve insulin sensitivity more than semaglutide, possibly due to the combined effects of GLP-1 and GIP receptor activation.

5. **Gastrointestinal Side Effects**: - While both medications can cause gastrointestinal side effects such as nausea, vomiting, and diarrhea, the specific profile and severity of these side effects may vary between the two drugs. Some patients may tolerate one better than the other.

In summary, tirzepatide's dual receptor agonism offers potential advantages in glucose control, weight loss, and insulin sensitivity over semaglutide, which targets only the GLP-1 receptor.

**What is the average weight loss with semaglutide?**

The average weight loss with Wegovy/ semaglutide, based on clinical trial data, is:

- **Around 15% of initial body weight**: In the *Once-Weekly Semaglutide in Adults with Overweight or Obesity* trial, participants taking Wegovy lost an average of 15% of their initial body weight over a 68-week period.

- **Approximately 15-20 kg (33-44 lb)**: This corresponds to an average weight loss of about 15 to 20 kg (33 to 44 lb), depending on that patient's initial weight.

Wegovy can be a highly effective treatment for obesity, leading to substantial weight loss when combined with lifestyle changes such as diet and exercise.

**What is the average weight loss with tirzepatide?**

The average weight loss with Mounjaro/ tirzepatide based on clinical trial data, is: has shown *SURMOUNT-1 - Tirzepatide Once Weekly for the Treatment of Obesity* trial. The average weight loss with tirzepatide varies based on the dosage and the duration of treatment. Here are the key findings:

**Around 15 - 18% of initial body weight*: - In the *Tirzepatide Once Weekly for the Treatment of Obesity* trial, participants taking Mounjaro lost and average of between 15 - 18% of their initial body weight over a 72-week period.

**Weight Loss in kilogram (Pounds)**: - In the same trial, the weight loss ranged from about 8.2 kg (18 lb) for the 5 mg dose to 11.3 kg (25 lb) for the 15 mg dose.

**Higher Doses and Longer Duration**: - In the SURMOUNT-1 trial, The average weight loss for those on the highest dose (15 mg) was up to 22.5% of their initial body weight over 72 weeks, which equates to an average loss of about 24 kg (53 lb).

These results indicate that tirzepatide can lead to substantial weight loss, often exceeding the results seen with other medications for weight management, including semaglutide. The dual action on GLP-1 and GIP receptors likely contributes to these significant outcomes.

These drugs are exciting, already helping very many patients under the care of Dr Philip Kelly and Dr Martin Whyte at LondonSwissMedical. We work closely with specialist dieticians, experienced in the close supervision which has helped patients make the most of these medications. We are also supported by excellent laboratories in London, and across the UK, to help you understand how these medications would work for you, whether that is your weight and body mass index (BMI - height in kilogram, divided by the square of your height in meters), waist circumferance, HbA1c and plasma glucose, cholesterol and lipids, liver fat and enzymes in metabolic dysfunction associated liver disease (MASLD - previously called non-alcoholic steatohepatitis/ NASH), your sleep, libido and erections, or your periods and fertility. There is so much more to your health, and we look after the whole of you.

If you want to know more about your health book an appointment.

Your Health is Our Concern.

Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med 2021; 384:989-1002

Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022; 387:205-216

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