What is GLP-1

Glucagon-like peptide-1 (GLP-1) is a peptide hormone produced in the intestines in response to meals. Semaglutide and Tirzepatide are analogs of human GLP-1 that is modified to have a longer half-life. These analogs have been shown to induce weight loss and reduce blood sugar through: decreasing appetite and food cravings, signaling the pancreas to secrete insulin, and slowing gastric emptying.  GLP-1 injections alone do not cause weight loss. They work at the source by decreasing your appetite and interest in overeating. Tirzepatide stimulates both the GLP-1 receptor and the Gastric Inhibitory Peptide (GIP) receptor which has similar effects.

FDA Approvals

• Semaglutide

  • Ozempic® was approved as a once-weekly injection to treat type 2 diabetes in patients ≥18 yo (2017).

  • Wegovy® was approved for weight loss in patients ≥12 yo with obesity (BMI ≥30) or overweight (BMI ≥27) who also have a weight-related medical issue such as diabetes, hypertension, sleep apnea, high cholesterol (2021).

• Tirzepatide

  • Mounjaro® was FDA approved in the treatment of type 2 diabetes in patients ≥18 yo (2022).

  • Zepbound® was FDA approved in the treatment of obesity (BMI ≥30) or overweight (BMI ≥27) who also have a weight-related medical issue in 2023.

Common benefits of GLP-1 peptides

• Dramatically reduced appetite. GLP-1 analogs reduce cravings for dairy, starchy, salty, and spicy foods. They can also reduce the desire for high-fat, non-sweet foods.

• Average weight loss for overweight or obese adults taking Semaglutide was 14.9% 1

• Average weight loss for overweight or obese adults taking Tirzepatide was 24.0% 2

• Rapid weight loss: ~90% of overweight patients lose 5-25% of their body weight

• Significant decreases in blood sugar, cholesterol, risk of heart attack, and hypertension.

• Reduced need for medications to lower blood pressure, blood sugar, and cholesterol

Other benefits

• Decreased Obstructive Sleep Apnea (66% reduction in severity with Tirzepatide) 3

• GLP-1 agonists can reduce ALT/AST levels and improve liver histology in patients with NAFLD 4

• Improved Kidney Function (eGFR), reduced risk of kidney disease progressing and kidney failure. 5

• Depression: GLP-1RAs induced significant reductions in the depression rating scales compared to control treatments. 6

• Decreased interest in substance use behaviors (alcohol, nicotine, etc.) 7

• Likely benefits in reducing gambling, shopping, emotional eating, and other compulsive behaviours.

1. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183
   (phase-1, placebo controlled, double-blind trial in 1961 adults)

2. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387(3):205-216. doi:10.1056/NEJMoa2206038
   (phase 3 double-blind, randomized, controlled trial in 2539 adults)

3. Malhotra A, Grunstein RR, Fietze I, et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity [published correction appears in N Engl J Med. 2024 Oct 17;391(15):1464. doi: 10.1056/NEJMx240005]. N Engl J Med. 2024;391(13):1193-1205. doi:10.1056/NEJMoa2404881

4. Kalogirou M, Sinakos E. Treating nonalcoholic steatohepatitis with antidiabetic drugs: Will GLP-1 agonists end the struggle?. World J Hepatol. 2018;10(11):790-794. doi:10.4254/wjh.v10.i11.790

5. Badve SV, Bilal A, Lee MMY, et al. Effects of GLP-1 receptor agonists on kidney and cardiovascular disease outcomes: a meta-analysis of randomised controlled trials. Lancet Diabetes Endocrinol. Published online November 25, 2024. doi:10.1016/S2213-8587(24)00271-7

6. Chen X, Zhao P, Wang W, Guo L, Pan Q. The Antidepressant Effects of GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis. Am J Geriatr Psychiatry. 2024;32(1):117-127. doi:10.1016/j.jagp.2023.08.010

7. Martinelli S, Mazzotta A, Longaroni M, Petrucciani N. Potential role of glucagon-like peptide-1 (GLP-1) receptor agonists in substance use disorder: A systematic review of randomized trials. Drug Alcohol Depend. 2024;264:112424. doi:10.1016/j.drugalcdep.2024.112424

Side Effects

• Typically occur when increasing dosages. Many side effects can be limited by staying at lower doses longer.

• The most common side effect is nausea, with about 28% of patients in clinical trials reporting this compared to placebo.

• Less common side effects included. diarrhea, fatigue, constipation, abdominal pain, headache, and acid reflux

• Rare side effects included dizziness, depression, bloating, dry mouth, metallic taste, and heartburn

• Serious side effects are very rare, but can include acute pancreatitis, cholecystitis, ileus (intestinal blockage)

• Patients who should not use Semaglutide and Tirzepatide include people who are not overweight, or who have type-I diabetes, medullary thyroid cancer, a history of allergic reaction to other GLP-1 medications, and those already taking other GLP-1 medications.