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SEMAGLUTIDE & TIRZEPATIDE

GLP-1 agonists were approved by the FDA for weight loss in late 2014. It’s a newer class of drugs better known for its ability to improve blood-sugar control. These medications  were actually designed to treat type II diabetes, but some have also been FDA approved to treat weight loss. The GLP-1 agonists we work with are called Semaglutide & Tirzepatide (coming Soon!). Semaglutide is also known Ozempic or Wegovy. Tirzepatide is known as Mounjaro.

Benefits of GLP-1 Agonists

  • Helps slow food leaving your stomach
  • Helps prevent your liver from making too much sugar
  • Helps the pancreas produce more insulin when your blood sugar levels are high
  • Can help control blood glucose
  • Can reduce hyperglycemia, especially after meals
  • Can reduce fasting insulin and fasting glucose
  • Can reduce hemoglobin A1c
  • Can decrease appetite and caloric intake, while inhibiting weight gain
  • Has been shown to lower triglyceride levels and oxidative stress from high LDL
  • Has been shown to help induce weight loss in obese patients with higher dosing
  • Helps decrease leptin and increase leptin sensitivity
  • Can increase the conversion of white fat to brown fat

The addition of GLP-1 agonists to calorie restriction significantly augmented weight loss and improved insulin resistance, systolic blood pressure, glucose, and triglyceride concentration in this population at high risk for development of type 2 diabetes and cardiovascular disease.

What is Semaglutide & Tirzepatide?

These medications fall into the GLP-1 agonist class of drugs. GLP-1 stands for Glucagon-like peptide 1. GLP-1 is secreted when we consume carbohydrates and fats. It stimulates release of insulin, suppression of glucagon, slower gastric emptying, and increased satiety (fullness). Tirzepatide is also knows as a glucose-dependent insulinotropic polypeptide (GIP).  

Both of those hormones are released when we eat food. When eat carbs or sugar our body recognizes these nutrients and it releases the GLP-1 and GIP hormones that then stimulate our pancreas to release insulin. The appetite center in the brain also recognizes this and turns on the "sense of fullness" sensation so we stop eating. 

Both Semaglutide & Tirzepatide affect these receptors and causes changes to various hormones involved in regulating appetite and body weight: insulin, glucagon, and leptin.

Leptin

Leptin is a hormone that is produced by your body's fat cells. It is supposed to tell your brain that — when you have enough fat stored — you don't need to eat and can burn calories at a normal rate. Leptin's main role is long-term regulation of energy, including the number of calories you eat and expend, as well as how much fat you store in your body. People who have a lot of excess weight also have high levels of leptin.

Our brains should know that we have plenty of energy stored. Sometimes our leptin signaling doesn’t work and we develop leptin resistance. This is when we have an abundance of leptin, but the brain doesn't see or recognize it. When your brain doesn't receive the leptin signal, it mistakenly thinks that your body is starving even though it has plenty of energy stored. This condition is now believed to be one of the main biological contributors to obesity.

Leptin can determine if you lose weight and how much. GLP-1 agonists like Semaglutide and Tirzepatide can help lower leptin resistance. It does this by helping to change the biochemistry of the body and at the same time decrease the rise in leptin resistance once you start losing weight. This helps to naturally reduce your appetite, increase your metabolism and increase fat burning capacity. Correcting this allows for weight loss to occur and more importantly helps you keep off the weight that you have lost. 

Insulin

Semaglutide and Tirzepatide also help reduce insulin resistance. Insulin resistance is when cells in your body start resisting or ignoring the signal that insulin is trying to send out—which is to help glucose enter our cells from the bloodstream. Insulin is also a very important hormone involved in weight loss. High insulin levels make it almost impossible for your body to burn fat.

Insulin blocks an enzyme called hormone-sensitive lipase (HSL). This hormone is responsible for the mobilization of fatty acids from fat cell stores. If levels of insulin are high, it blocks this enzyme. Studies show that HSL is decreased in patients with type 2 diabetes mellitus, and this may be a consequence of elevated insulin levels. Excess insulin also has the added problem of promoting fat storage. 

​Semaglutide and Tirzepatide help sensitize the body to insulin levels and helps to lower blood glucose levels. It also helps reduce fasting insulin and glucose levels. Once insulin levels are stabilized to normal levels this may also improve other hormone imbalances (testosterone for example) which will naturally result in weight loss and a reduction in symptoms associated with those imbalances.

GLP-1 agonists like Semaglutide and Tirzepatide help reduce insulin resistance and lower blood sugar. This then activates hormone-sensitive lipase and results in more fat burning activity over time. 

Glucagon

Glucagon helps increase blood sugar levels while insulin lowers blood sugar levels. They are opposites. For hormone-sensitive lipase (fat burning enzyme) to be activated, insulin and glucagon (from glycogen stores) need to be at relatively low levels. High glucagon can also interfere with normal glucose control which in turn can alter how your body burns energy. ​

Semaglutide and Tirzepatide and other GLP-1 agonists help reduce glucagon levels while simultaneously reducing insulin resistance. Both of these changes promote more normal blood glucose levels and help promote proper liver metabolism of glucose and help adipose tissue burn fat. ​Glucagon is just as important in the regulation of glucose levels in the body. Treating both insulin and glucagon leads to normal glucose levels and weight loss.

Semaglutide and Tirzepatide helps naturally improve your metabolism over time, probably through its effects on leptin levels. Leptin feeds back to your hypothalamus and helps set your body set point - the number of calories your body burns which in terms alters your appetite.

Remember, our body is constantly trying to match the number of calories you burn to the number of calories that you consume. 

Dosing: 

Tirzepatide is dosed at 5-15mg per week

Semaglutide is dosed at 0.5-2.4mg per week

What's important is when to increase your dose, how often you increase the dose, and when to dose the medication. The benefits listed above are only achieved at a certain minimum dose and this dose is different for each person. 

The medications come in a multi dose vial and is injected into your body daily or weekly depending on which one you take. We will work with you to reach the correct dose.

Side Effects of GLP-1 Agonists

In clinical trials, the most common side effects observed in patients treated with these medications were nausea, low blood sugar, diarrhea, constipation, vomiting, headache, decreased appetite, upset stomach, fatigue, dizziness, and abdominal pain.

In addition, some patients who took these medications reported other side effects including pancreatitis, gallbladder disease and renal impairment. You should stop taking it if you notice an increase in your resting heart rate that continues over time.

Check out our Weightloss Packages!

References

Dushay J, Gao C, Gopalakrishnan GS, et al. Short-term exenatide treatment leads to significant weight loss in a subset of obese women without diabetes. Diabetes Care. 2012;35(1):4-11. doi:10.2337/dc11-0931

Dushay J, Gao C, Gopalakrishnan GS, et al. Short-term exenatide treatment leads to significant weight loss in a subset of obese women without diabetes. Diabetes Care. 2012;35(1):4-11. doi:10.2337/dc11-0931

Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, McGowan BM, Rosenstock J, Tran MTD, Wadden TA, Wharton S, Yokote K, Zeuthen N, Kushner RF; STEP 1 Study Group. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10. PMID: 33567185.

Wadden TA, Bailey TS, Billings LK, Davies M, Frias JP, Koroleva A, Lingvay I, O'Neil PM, Rubino DM, Skovgaard D, Wallenstein SOR, Garvey WT; STEP 3 Investigators. Effect of Subcutaneous Semaglutide vs Placebo as an Adjunct to Intensive Behavioral Therapy on Body Weight in Adults With Overweight or Obesity: The STEP 3 Randomized Clinical Trial. JAMA. 2021 Apr 13;325(14):1403-1413. doi: 10.1001/jama.2021.1831. PMID: 33625476; PMCID: PMC7905697.

O'Neil PM, Birkenfeld AL, McGowan B, Mosenzon O, Pedersen SD, Wharton S, Carson CG, Jepsen CH, Kabisch M, Wilding JPH. Efficacy and safety of semaglutide compared with liraglutide and placebo for weight loss in patients with obesity: a randomised, double-blind, placebo and active controlled, dose-ranging, phase 2 trial. Lancet. 2018 Aug 25;392(10148):637-649. doi: 10.1016/S0140-6736(18)31773-2. Epub 2018 Aug 16. PMID: 30122305.

Gallwitz B, Giorgino F. Clinical Perspectives on the Use of Subcutaneous and Oral Formulations of Semaglutide. Front Endocrinol (Lausanne). 2021 Jun 29;12:645507. doi: 10.3389/fendo.2021.645507. PMID: 34267725; PMCID: PMC8276717.

Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, Liu B, Cui X, Brown K; SURPASS-2 Investigators. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021 Aug 5;385(6):503-515. doi: 10.1056/NEJMoa2107519. Epub 2021 Jun 25. PMID: 34170647.

Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216. doi: 10.1056/NEJMoa2206038. Epub 2022 Jun 4. PMID: 35658024.

Heise T, Mari A, DeVries JH, Urva S, Li J, Pratt EJ, Coskun T, Thomas MK, Mather KJ, Haupt A, Milicevic Z. Effects of subcutaneous tirzepatide versus placebo or semaglutide on pancreatic islet function and insulin sensitivity in adults with type 2 diabetes: a multicentre, randomised, double-blind, parallel-arm, phase 1 clinical trial. Lancet Diabetes Endocrinol. 2022 Jun;10(6):418-429. doi: 10.1016/S2213-8587(22)00085-7. Epub 2022 Apr 22. PMID: 35468322.

GLP-1 agonists: Diabetes drugs and weight loss

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