GLP-1 medications like Ozempic (semaglutide) and Mounjaro (tirzepatide) have recently been gaining popularity and media attention for their beneficial effects in treating diabetes and promoting weight loss. This article will provide a comprehensive guide from a pharmacist to anyone on a GLP-1 medication or thinking about starting one.
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What are GLP-1 medications?
GLP-1 is an abbreviation for Glucagon-Like Peptide-1 receptor agonist, which is a class of medications commonly used to treat diabetes and to assist with weight loss in patients with or without diabetes. This class of medications contains the popular semaglutide (Ozempic®, Wegovy®, Rybelsus®), tirzepatide (Mounjaro®, Zepbound®), liraglutide (Victoza®, Saxenda®), dulaglutide (Trulicity®), and exenatide (Byetta®, Bydureon®). Only semaglutide, tirzepatide, and liraglutide are FDA approved for weight loss, but all of these medications are approved to treat type 2 diabetes.
How do GLP-1 medications work?
GLP-1 medications have multiple different mechanisms in the body that help with diabetes and weight loss, including:
- Increasing the amount of insulin made by the pancreas, which helps control blood sugar in patients with diabetes
- Decreasing the amount of excess sugar made by the pancreas, which helps control blood sugar in patients with diabetes
- Slowing down digestion from the stomach, which results in feeling full for longer after eating
- Signaling to your brain that you are full after eating, which helps suppress appetite and control cravings
Tirzepatide contains an extra mechanism of action that other GLP-1 medications do not, known as GIP (glucose-dependent insulinotropic polypeptide) agonism. This extra mechanism provides the following benefits:
- Greater appetite suppression and glucose control due to additive effects when combined with GLP-1 agonism
- Improving how fat cells respond to insulin, which provides more effective blood sugar control
- Promoting the breakdown of fat cells resulting in more effective weight loss
How effective are GLP-1 medications?
All GLP-1 medications have been proven to be effective for diabetes, and some have been studied and proven to be effective for weight loss as well. Below are details regarding their effectiveness in clinical trials.
GLP-1s for Weight loss
GLP-1s were studied for weight loss in patients 18 years old or older who are obese (BMI > 30 kg/m2) or overweight (BMI > 27 kg/m2) with at least one weight-associated condition, such as cardiovascular disease, high cholesterol, high blood pressure, obstructive sleep apnea, or type 2 diabetes.
In a study of 1,961 patients assigned to take either semaglutide or placebo for 68 weeks, 86.4% of the patients on semaglutide achieved at least 5% weight loss. In addition, 69.1% achieved at least 10% weight loss, and 50.5% achieved at least 15% weight loss. The most frequently reported side effects in this study were mild to moderate nausea, diarrhea, vomiting, and constipation.
In a study of 2,539 patients assigned to take either tirzepatide or placebo for 72 weeks, the average weight loss achieved for patients taking tirzepatide 5 mg was 15%. Patients taking tirzepatide 10 mg achieved an average of 19.5% weight loss, and patients taking tirzepatide 15 mg achieved an average of 20.9% weight loss. The most frequently reported side effects were mild to moderate nausea, diarrhea, and constipation.
In a study of 3,731 patients assigned to take either liraglutide or placebo, 63.2% of patients taking liraglutide lost at least 5% of their body weight and 33.1% of patients lost at least 10% of their body weight. The most frequently reported side effects were mild to moderate nausea and diarrhea.
In a study comparing the effects of semaglutide and tirzepatide for weight loss, those receiving tirzepatide were more likely to achieve 5% or greater, 10% or greater, and 15% or greater weight loss and experienced larger reductions in body weight at 3, 6, and 12 months. Rates of reported side effects were similar between the two groups.
GLP-1s for Diabetes
While the American Diabetes Association (ADA) recommends personalized goals for the care of diabetes, all GLP-1 medications have shown to be effective. The 2024 Standards of Care in Diabetes does emphasize use of certain GLP-1 medications over others for certain goals. Semaglutide, liraglutide, and dulaglutide have all shown to reduce the occurrence of major cardiovascular events like heart attack, stroke, and death in patients with diabetes, while tirzepatide is currently being studied for the same. Semaglutide, tirzepatide, and high dose dulaglutide have been deemed to have very high likelihood of achieving adequate blood sugar control, while other GLP-1s have been deemed highly likely. GLP-1 medications are recommended in the ADA Standards of Care for those with cardiovascular disease, heart failure, and/or kidney disease to reduce the risk of adverse events due to these conditions. GLP-1s are also recommended for blood sugar control in those who have a goal of weight loss in addition to managing their diabetes.
Who should not take GLP-1 medications?
GLP-1 medications should not be taken by anyone with a personal history or family history of medullary thyroid cancer, as development of these tumors were noted during early animal studies. These medications should also be avoided in anyone with multiple endocrine neoplasia syndrome type 2 due to increased risk. GLP-1 medications should be stopped if pancreatitis develops, and should likely be avoided in anyone with pre-existing gastroparesis.
What are the side effects of GLP-1 medications?
The most commonly reported side effects of GLP-1 medications are gastrointestinal symptoms like nausea, abdominal pain, and constipation. These are usually observed at the beginning of treatment and after dose increases, but typically go away with time. Acute pancreatitis, gallbladder disease, and stomach paralysis have also been rarely reported with GLP-1 use.
How are GLP-1 medications taken?
Most GLP-1 medications are given via subcutaneous injection, which means an injection under the skin but not in the muscle. Most injectable GLP-1s are given once per week, while liraglutide is given once per day. Semaglutide is also available as a once-daily oral capsule (Rybelsus®) for the treatment of diabetes.
Lifestyle tips to get the best results
For the best results while taking any GLP-1 medication, a healthy diet and adequate exercise are recommended. The American Heart Association specifically recommends consuming a diet that emphasizes intake of vegetables, fruits, whole grains, legumes, and healthy protein. They also recommend limiting intake of saturated fat, sweets, sugar-sweetened beverages, and red meat. For exercise, the American Heart Association recommends three to four 40-minute sessions of moderate to vigorous intensity exercise per week for most adults. These lifestyle modifications will help with both weight loss and diabetes in addition to GLP-1s.
Conclusion
GLP-1 medications have proven to be effective for management of diabetes as well as for weight loss in those without diabetes, especially when combined with a healthy diet and adequate exercise. GLP-1 medications should not be taken by people with a history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2. GLP-1s are generally well tolerated, with most gastrointestinal side effects subsiding over time.
If you have additional questions on GLP-1 medications or just want more information on diabetes or weight loss treatment in general you can connect with a licensed pharmacist on-demand using Medidex Connect.
References
- Min T, Bain SC. The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials. Diabetes Ther. 2021 Jan;12(1):143-157. doi: https://doi.org/10.1007/s13300-020-00981-0
- Pirro V, Roth KD, Lin Y, et al. Effects of Tirzepatide, a Dual GIP and GLP-1 RA, on Lipid and Metabolite Profiles in Subjects With Type 2 Diabetes. J Clin Endocrinol Metab. 2022 Jan 18;107(2):363-378. doi: https://doi.org/10.1210/clinem/dgab722
- Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021 Mar 18;384(11):989-1002. doi: https://doi.org/0.1056/NEJMoa2032183
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216. doi: https://doi.org/10.1056/NEJMoa2206038
- Pi-Sunyer X, Astrup A, Fujioka K, et al. A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management. N Engl J Med. 2015 Jul 2;373(1):11-22. doi: https://doi.org/10.1056/NEJMoa1411892
- Rodriguez PJ, Goodwin Cartwright BM, Gratzl S, et al. Semaglutide vs Tirzepatide for Weight Loss in Adults With Overweight or Obesity. JAMA Intern Med. 2024;184(9):1056–1064. doi: https://doi.org/10.1001/jamainternmed.2024.2525
- American Diabetes Association Professional Practice Committee. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2024. Diabetes Care. 2024 Jan 1;47(Suppl 1):S158-S178. doi: https://doi.org/10.2337/dc24-S009
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