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Tirzepatide, Semaglutide: A Break-Through for Weight Loss… but how?

Introduction

Weight control has been a struggle for many of us. From sedentary lifestyles, and increased stress, to the standard American diet we are set up for failure in our quest to achieve the healthy weight we dream of. Historically there have not been the treatment options we need to finally lose weight and keep it off. Many of the treatments included major side effects, many contraindications, and promises of modest results at best. That changed with Semaglutide and just when we thought it couldn’t get any better Tirzepatide came on board and increased the ante. We will explore in this article how tirzepatide works and what it means to us as we face our weight loss journey.

Understanding GLP-1 and GIP

GLP-1: GLP-1 or Glucagon-like peptide-1 are well known today for their ability to promote weight loss. They achieve this by increasing satiety, slowing gastric emptying, and reducing food intake. Combining this with their ability to improve glucose homeostasis makes it the most effective weight loss medication in history. However, like all medications, with the positives comes the negatives in the form of side effects. These side effects include nausea, vomiting, constipation and diarrhea.

GIP: GIP Glucose-dependent insulinotropic polypeptide is another hormone that is not as widely known. This hormone helps to increase the secretion of insulin and improves the metabolism. Additionally, it helps to facilitate the storage of dietary lipids (fats) in white adipose tissue (WAT) and enhances lipid buffering capacity in these tissues.

That was a lot of technical jargon!

Simply put, it helps your body release and use insulin better which helps to control your blood sugar. Additionally, it supports your body in healthily storing fat preventing it from building up around places that can cause problems such as your liver.

How do these peptides help with weight loss

GLP-1

Satiety: GLP-1 in the body is one of the hormones responsible for telling your body you’re full and to stop eating. This reduces hunger which in turn reduces how much you eat leading to weight loss.

Gastric Emptying: Additionally, this hormone slows down how quickly food leaves your body (gastric emptying) helping to control spikes in your blood sugar and helping you feel full longer after eating.

Insulin Secretion: Lastly, GLP-1 improves our blood sugar by improving our output of insulin in response to blood sugar.

GIP

Fat Storage and Buffering: GIP on the other hand healthily helps your body store fat reducing the fat building up around organs which can lead to problems over time.

Insulin Sensitivity: GIP also helps your body utilize insulin better helping to control the insulin resistance that is so prevalent in weight gain.

CNS Effects: Lastly GIP acts on the central nervous system helping to aid in the regulation of appetite and further reducing body weight.

Synergistic Effects

When combined, these peptides create something greater than expected. This results in greater weight loss, better glucose control, better insulin sensitivity, and better overall metabolic health.

Lastly, what we find is that the side effects that have prevented some from finding success on GLP-1 medications such as semaglutide are reduced. Meaning more people can use the medication and stay on them longer.

Weight Loss of Semaglutide vs Tirzepatide

Tirzepatide: This dual GIP/GLP-1 receptor agonist has shown superior efficacy in weight loss compared to GLP-1RAs alone. In a 26-week trial, tirzepatide not only significantly reduced HbA1c levels but also promoted greater weight loss than dulaglutide, a GLP-1RA​​.

 

Semaglutide vs. Tirzepatide: Recent studies have highlighted the comparative weight loss effects of semaglutide, a potent GLP-1RA, and tirzepatide.

In a 40-week clinical trial, patients treated with semaglutide (2.4 mg) experienced an average weight loss of approximately 14.9% of their body weight.

In contrast, patients treated with tirzepatide (15 mg) achieved an even greater average weight loss of about 21.4%​​. This significant difference underscores the enhanced efficacy of tirzepatide, likely due to the synergistic action of GIP and GLP-1.

Conclusion

We are just beginning to scratch the surface of what these medications do and how they can help us to lose weight. Finding the right medication often comes down to how much you need to lose, underlying disease processes such as insulin resistance that may benefit from the enhanced effects of tirzepatide vs semaglutide, and your body’s ability to handle the side effects of the medications. When combined with the proper diet, exercise, stress reduction, and sleep promotion lifestyle changes it’s possible to find lasting success with the aid of these state-of-the-art treatments for weight loss.

References

  1. Samms RJ, Coghlan MP, Sloop KW. How May GIP Enhance the Therapeutic Efficacy of GLP-1? Trends Endocrinol Metab. 2020;31(6):410-418. doi:10.1016/j.tem.2020.02.006.
  2. Finan B, Ma T, Ottaway N, et al. Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans. Sci Transl Med. 2013;5(209):209ra151. doi:10.1126/scitranslmed.3007218.
  3. Frias JP, Nauck MA, Van J, et al. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: A randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet. 2018;392(10160):2180-2193. doi:10.1016/S0140-6736(18)32260-8.
  4. Kim SJ, Nian C, McIntosh CH. Activation of lipoprotein lipase by glucose-dependent insulinotropic polypeptide in adipocytes: A role for a protein kinase B, LKB1, and AMP-activated protein kinase cascade. J Biol Chem. 2007;282(12):8557-8567. doi:10.1074/jbc.M610579200.
  5. Rosenstock J, Wysham C, Frías JP, et al. Efficacy and Safety of Tirzepatide in Patients with Type 2 Diabetes. N Engl J Med. 2021;385(6):502-514. doi:10.1056/NEJMoa2107519.