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Dulaglutide vs. Semaglutide: Differences and Similarities Between the Two Medications

Written on September 12, 2023 by Sendra Yang, PharmD, MBA. To give you technically accurate, evidence-based information, content published on the Everlywell blog is reviewed by credentialed professionals with expertise in medical and bioscience fields.

Table of contents

The class of medications known as GLP1 drugs has been in the news lately.[1,2] GLP1s, or glucagon-like peptide-1 receptor agonists, are also called GLP-1 receptor agonists, incretin mimetics, or GLP-1 analogs.[3,4] There are several medications in the GLP1 drug class. The two medications that will be the focus of this article are dulaglutide and semaglutide. Continue reading to understand the differences and similarities between dulaglutide vs. semaglutide.

FDA-Approved Indications

Dulaglutide and semaglutide are both currently marketed in the United States but have different approval dates. Dulaglutide was initially approved by the U.S. Food and Drug Administration (FDA) in 2014 for treating type 2 diabetes under the brand name Trulicity®.[5,6] Semaglutide was FDA-approved to treat type 2 diabetes and marketed as Ozempic® (approved in 2017) and Rybelsus® (approved in 2019).[7-10] Additionally, Trulicity® and Ozempic® are approved to reduce the risk of major cardiovascular events (such as heart attack and stroke) in adults with type 2 diabetes who have established cardiovascular disease.[6,8] Both dulaglutide and semaglutide medications are indicated to be used in combination with diet and exercise in type 2 diabetics.[6,8,10]

Then, in 2021, semaglutide, under the brand name Wegovy®, became the first drug since 2014 to be approved by the FDA for chronic weight management in obese and overweight patients with diet and exercise.[7,11] Overweight patients must have at least one weight-related condition, such as high blood pressure or type 2 diabetes. Wegovy® is also approved for use in pediatric patients 12 years and older who are overweight.[11] Currently, dulaglutide is not FDA-approved for weight management.[6]

Dosage and Administration

There are similarities and differences in dosage and administration with dulaglutide vs. semaglutide. Dulaglutide is only available at this time as a once-weekly subcutaneous injection.[6] Semaglutide is available as once-weekly subcutaneous injections (Ozempic® and Wegovy®) and an oral daily tablet (Rybelsus®).[8,10,11] Both dulaglutide and semaglutide require a starting initial dose, with dose increases to reach a recommended dose. The dulaglutide and semaglutide injection formulations will involve a dose increase weekly based on the indication until the appropriate dose is reached. The semaglutide oral formulation requires a dose increase 30 days after the starting dose, and the dose can be increased further if additional glucose control is needed after at least 30 days.

Mechanism of Action

Dulaglutide and semaglutide are both GLP1 drugs synthesized and manufactured in the lab and thus work primarily the same.[6,8,10,11] Both of these medications mimic the GLP1 naturally produced in the human body. A difference between the two medications is in the genetic pattern of the synthesized medications. Dulaglutide has 90% similar genetic makeup to the human GLP-1, while semaglutide has 94%. They work by activating GLP1 receptors in the body to increase insulin release from the pancreatic beta-cells, decrease the breakdown of glucose stores from the liver, and slow gastric emptying.[6,8,10,11] Additionally, semaglutide can affect appetite and caloric intake by involving different pathways in the brain.[11]

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Safety Information

The side effects between dulaglutide and semaglutide are similar.[6,8,10,11] The most common side effects seen in patients taking either medication are nausea, diarrhea, vomiting, and abdominal pain. Both drugs have a boxed warning, or a serious FDA safety warning, for the risk of thyroid C-cell tumors. Dulaglutide and semaglutide should be avoided in patients with a personal or family history of certain thyroid cancers. Additional warnings and precautions include pancreatitis, gall bladder disease, kidney damage, increased heart rate, and low blood glucose levels and eye disorder in type 2 diabetics. Additionally, dulaglutide and semaglutide should be avoided if you have a hypersensitivity reaction to the medication.[6,8,10,11] You should avoid using semaglutide with other products that contain the medication or in combination with other GLP-1 drugs.[10,11]

Clinical Trial: Dulaglutide Vs. Semaglutide in Type 2 Diabetic Adult Patients

In a clinical trial, semaglutide showed superiority over dulaglutide to improve glucose control and weight loss greater than 5% in type 2 diabetic adult patients.[12] The study was randomized and open-label, meaning the participants knew what medication they received. It was conducted at 194 hospitals in 16 countries with 1201 patients assigned to semaglutide 0.5 mg, semaglutide 1 mg, dulaglutide 0.75 mg, or dulaglutide 1.5 mg. Participants reported gastrointestinal disorders as the most frequent adverse event in all the groups.

GLP-1 Medications and At-Home Lab Testing With Everlywell

Both GLP-1 drugs, dulaglutide and semaglutide, are available with a prescription from a healthcare provider.[6,8,10,11] If you have questions and want to discuss your weight loss goals, you can consider a telehealth option with Everlywell through the Virtual Care Visit platform. A Weight Care+ program is available that pairs online GLP-1 prescriptions with regular clinical care, lab testing, and support for related conditions. Access to GLP-1 prescriptions are available if you are a qualified candidate. The program also offers regular one-on-one virtual visits with a licensed healthcare provider to help support you on your weight loss journey. You can also get support for conditions like high cholesterol and prediabetes.

Everlywell also has an HbA1c at-home lab test that helps monitor your blood sugar levels to better understand your body’s blood sugar control. This particular test takes a look at your average blood sugar levels over the past three months. You can collect your sample for the test from the comfort of your own home and mail it to a certified lab for testing.

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  1. Kolata G. We know where new weight loss drugs came from, but not why they work. The New York Times. https://www.nytimes.com/2023/08/17/health/weight-loss-drugs-obesity-ozempic-wegovy.html. August 17, 2023. Accessed August 25, 2023.
  2. Bloomberg. www.bloomberg.com/news/articles/2023-08-18/glp-1-drugs-are-coming-and-they-could-change-everything#xj4y7vzkg. Accessed August 25, 2023.
  3. Latif W, Lambrinos KJ, Rodriguez R. Compare and Contrast the Glucagon-Like Peptide-1 Receptor Agonists (GLP1RAs) [Updated 2023 Mar 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK572151/
  4. Collins L, Costello RA. Glucagon-Like Peptide-1 Receptor Agonists. [Updated 2023 Jan 13]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551568/
  5. Press announcements - FDA approves Trulicity to treat type 2 diabetes. Archive. https://wayback.archive-it.org/7993/20170112023822/http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm415180.htm. Accessed August 25, 2023.
  6. DailyMed - trulicity- dulaglutide injection, solution. U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=463050bd-2b1c-40f5-b3c3-0a04bb433309. Accessed August 25, 2023.
  7. FDA approves new drug treatment for Chronic Weight Management, first since 2014. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-new-drug-treatment-chronic-weight-management-first-2014. Accessed August 25, 2023.
  8. DailyMed - OZEMPIC®- semaglutide injection, solution. U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=adec4fd2-6858-4c99-91d4-531f5f2a2d79. Accessed August 25, 2023.
  9. FDA approves first oral GLP-1 treatment for type 2 diabetes. U.S. Food and Drug Administration. https://www.fda.gov/news-events/press-announcements/fda-approves-first-oral-glp-1-treatment-type-2-diabetes. Accessed August 25, 2023.
  10. DailyMed - Rybelsus®- oral Semaglutide Tablet. U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=27f15fac-7d98-4114-a2ec-92494a91da98. Accessed August 25, 2023.
  11. DailyMed - Wegovy®- semaglutide injection, solution. U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b. Accessed August 25, 2023.
  12. Pratley RE, Aroda VR, Lingvay I, Lüdemann J, Andreassen C, Navarria A, Viljoen A; SUSTAIN 7 investigators. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol. 2018;6(4):275-286. doi: 10.1016/S2213-8587(18)30024-X
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