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Semaglutide for Weight Loss

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Two new medications have recently entered the limelight of medical weight loss. Championed by celebrities and influencers, everyone is asking their doctor for one or both of these substances to help them lose weight, but are these drugs the right choice for your patients?

The drugs in question are Semaglutide (brand names: Wegovy, Ozempic) & Tirzepatide (brand name: Mounjaro). Both of these drugs are FDA approved medications for Type 2 Diabetes, given as a weekly subQ injection.

Sermorelin & Tirzepatide Side Effects

Nearly all FDA-approved drugs have side-effects, and semaglutide/tirzepatide are no exception:

Semaglutide side effects:

  • Nausea
  • Vomiting
  • Diarrhea
  • Abdominal pain
  • Constipation
  • Heartburn
  • Burping

Tirzepatide side effects:

  • Nausea
  • Vomiting
  • Diarrhea
  • Loss of appetite
  • Stomach pain
  • Constipation
  • Upset stomach

To help their patients with these side effects many physicians are recommending digestive aids such as enzymes and probiotics.

How do they work?

Semaglutide and Tirzepatide work in very similar ways. Both Semaglutide and Tirzepatide are GLP-1 agonists; Tirzepatide is also a GIP agonist.

AGONIST: BIOCHEMISTRY
A substance which initiates a physiological response when combined with a receptor.

GLP-1 (glucagon-like peptide-1) and GIP ( glucose-dependent insulinotropic peptide  ) are normally stimulated by the presence of food in the small intestine. GLP-1 and GIP are both known as incretins, which are defined as gut hormones that can increase the amount of insulin released from the pancreas (Stipanuk & Caudill,510). All incretins control insulin and a satiety signal, and therefore have an impact on adiposity and glucose levels.

Do they work for weight loss?

Double-blind studies (published in the New England Journal of Medicine) appear to show positive effects on weight loss from both Semaglutide and Tirzepatide compared to placebo.

SEMAGLUTIDE resulted in weight reductions of 5% (1047 vs 182), 10% (893 vs 69), & 15% (612 vs 28) for more patients than placebo.

“Nausea and diarrhea were the most common adverse events with semaglutide; they were typically transient and mild-to-moderate in severity and subsided with time. More participants in the semaglutide group than in the placebo group discontinued treatment owing to gastrointestinal events (59 [4.5%] vs. 5 [0.8%])”

Wilding, J. et al. (2021).

TIRZEPATIDE resulted in weight reductions of 5% (89% vs 35%), & 20% (50% vs 3%) for more patients than placebo.

“The most common adverse events with tirzepatide were gastrointestinal, and most were mild to moderate in severity, occurring primarily during dose escalation. Adverse events caused treatment discontinuation in 4.3%, 7.1%, 6.2%, and 2.6% of participants receiving 5-mg, 10-mg, and 15-mg tirzepatide doses and placebo, respectively.”

Jasterboof, A. et al. (2022).

What does Semaglutide cost?

Semaglutide Ozempic injection
Semaglutide Ozempic injection

The average retail (patient) cost of semalutide (Ozempic) and tirezepatide (Mounjaro) is $1,172 for a 4-week supply[depending on dosage] (GoodRx, 2023). While these drugs are approved for treatment of type 2 diabetes, insurance may not cover the cost of these medications for weight loss. Without insurance, semaglutide or tirezepatide could cost a patient over $14,000 per year.

NATURAL ALTERNATIVES TO SEMAGLUTIDE & TIRZEPATIDE

As mentioned previously, the primary mechanism of action of these drugs is to increase activation of GLP-1. GLP-1 is normally activated by the presence of food in the gut, but there are other substances which can influence this incretin such as Momordica charantia and Gymnema Sylvestre.

Momordica charantia (Bitter Gourd) has demonstrated hypoglycemic activity in a number of clinical studies, and is believed to act through a number of pathways, including acting on GLP-1. “Our data provide evidence that BG stimulates GLP-1 secretion which contributes, at least in part, to the antidiabetic activity of BG through an incretin effect” (Huang et al, 2013).

Gymnema Sylvestre has been used in ayurvedic medicine for over 2,000 years where it has been nicknamed the “sugar destroyer”. Part of Gymnema’s sugar destroying ability comes from GLP-1. A 2020 study concluded that Gymnema Sylvestre “has signicant antihyperglycemic activity through stimulation of GLP-1 release and its enhanced proglucagon expression in ileum followed by Insulin Receptor (IR) expression in pancreas” (Kilari et al, 2020).

Have a question about semaglutide for weight loss?

References:

Wilding, J. et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med; 384:989-1002 DOI: 10.1056/NEJMoa2032183 https://www.nejm.org/doi/full/10.1056/NEJMoa2032183

Jasterboof, A. et al. (2022). Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med; 387:205-216 DOI: 10.1056/NEJMoa2206038 https://www.nejm.org/doi/full/10.1056/NEJMoa2206038

Huang, T. N., Lu, K. N., Pai, Y. P., Chin Hsu, & Huang, C. J. (2013). Role of GLP-1 in the Hypoglycemic Effects of Wild Bitter Gourd. Evidence-based complementary and alternative medicine : eCAM2013, 625892. https://doi.org/10.1155/2013/625892

Kilari, Eswar & Putta, Dr. Swathi & Silakabattini, Kotaiah. (2020). Effect of Gymnema sylvestre on Insulin Receptor (IR) and Proglucagon Gene Expression in Streptozotocin Induced Diabetic Rats. Indian Journal of Pharmaceutical Education and Research. 54. s277-s284. 10.5530/ijper.54.2s.84.