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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. 

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 the development of type 2 diabetes and cardiovascular disease.

WHAT ARE GLP-1 Agonists?

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 the release of insulin, suppression of glucagon, slower gastric emptying, and increased satiety (fullness). 

Both of those hormones are released when we eat food. When eating 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 affect these receptors and causes changes to various hormones involved in regulating appetite and body weight: insulin, glucagon, and leptin.

 

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.

REFERENCES

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.

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.

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.

Nauck, M.A., D‘Alessio, D.A. Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes with unmatched effectiveness regrading glycaemic control and body weight reduction. Cardiovasc Diabetol 21, 169 (2022). https://doi.org/10.1186/s12933-022-01604-7

GLP-1 agonists: Diabetes drugs and weight loss

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