GLP-1 medications and exercise used together for type 2 diabetes: what to know

Written on February 22, 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.

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Table of contents

• About diabetes
• Type 2 diabetes
• GLP-1 medications
• How GLP-1 medications work
• Examples of GLP-1 medications
• Combination of GLP-1 medications and exercise
• Do GLP-1 agonists have cardiovascular benefits?
• Adverse reactions and potential safety issues of GLP-1 medications
• Key points
• Virtual care and questions about GLP-1 medications
• Related content

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About diabetes

Diabetes is a chronic disease where your body does not make enough or cannot use insulin, leading to high sugar levels in your blood [1]. Insulin is a hormone your pancreas produces to help uptake sugar into your cells for energy. The two most common types of diabetes are type 1 and 2.

The National Diabetes Statistics Report from the Centers for Disease Control and Prevention estimates that approximately 37 million people in the United States have diabetes [2]. Of these 37 million people, up to 95% have type 2 diabetes [3].

Type 2 diabetes

Type 2 diabetes is known as adult-onset diabetes because it is more common in adults, but it can also occur in children and young adults [4]. In type 2 diabetes, your body is not able to use insulin well and cannot sufficiently take sugar into your cells to use for energy.

Signs and symptoms of type 2 diabetes can develop over time. You may be living with type 2 diabetes and not know it. Signs and symptoms include [4]:

• Increased thirst
• Frequent urination
• Increased hunger
• Unintended weight loss
• Fatigue
• Blurred vision
• Slow healing sores
• Frequent infections
• Numbness or tingling in the hands or feet
• Areas of darkened skin, usually in the armpits and neck

Currently, there is no cure for type 2 diabetes [4,5]. Strategies for managing type 2 diabetes include losing weight, eating a well-balanced diet, and exercising [4]. However, sometimes changing your diet and exercising may not be enough to manage the condition. You may also need diabetes medications to help bring your sugars within a healthy range. Though there are many types of medications available, one drug class that can help you manage your type 2 diabetes is GLP-1 medications [5].

GLP-1 medications

GLP-1 medications are also known as glucagon-like peptide-1 (GLP-1) agonists, GLP-1 receptor agonists, incretin memetics, or GLP-1 analogs [5,6].

GLP-1 receptor agonists (GLP-1 RAs) are a category of medications used to treat type 2 diabetes in adults [5,6]. The first GLP-1 medication, exenatide, was approved by the US Food and Drug Administration (FDA) in April 2005 for the treatment of type 2 diabetes [7]. Though GLP-1 RAs are not first-line therapies, this class of medications is suggested for adult type 2 diabetics with cardiovascular risks, is preferred to insulin when possible, and is recommended in combination therapy with insulin if insulin must be used [6].

How GLP-1 medications work

GLP-1 medications act like naturally producing GLP-1 hormones in the body [6,8]. GLP-1 helps to regulate glucose or sugar levels in the body. Carbohydrates and fats in the diet stimulate the release of GLP-1 hormones. GLP-1 binds and activates the GLP-1 receptors to enhance insulin secretion and synthesis from the pancreas by promoting beta cells, suppressing glucagon secretion, slowing gastric emptying, and reducing food intake by decreasing appetite. Thus, GLP-1 RAs help improve blood sugar control and can reduce weight in type 2 diabetics.

Examples of GLP-1 medications

Most GLP-1 medications or GLP-1 RAs are injectables [5-8]. The only approved oral GLP-1 RA is semaglutide, a once-a-day pill.

The available GLP-1 RA injectables are short or long-acting, and include [5,8-14]:

• Dulaglutide: Long-acting, once weekly
• Exenatide: Short-acting, twice a day
• Exenatide extended release: Long-acting, once weekly
• Liraglutide: Long-acting, once a day
• Lixisenatide: Short-acting, once a day
• Semaglutide: Long-acting, once weekly

Combination of GLP-1 medications and exercise

Non-medication management strategies for type 2 diabetes involve lifestyle modifications like diet and exercise. Exercise or physical activity is essential as part of the therapy for managing type 2 diabetes. Moderate-intensity activities, such as brisk walking, for about 150 minutes per week have shown beneficial effects on type 2 diabetes [15].

Combining GLP-1 medications with exercise has a synergistic effect to help lower glucose levels in the body. GLP-1 medications are approved for use with diet and exercise to treat type 2 diabetes [9-14]. Exercise in combination with GLP-1 medications appears to enhance the GLP-1 function leading to better sugar control in type 2 diabetics, though the exact way it works is not clear [16]. A 16-week study found that liraglutide combined with exercise achieved close to normal hemoglobin A1c levels with a reduction in weight when compared to placebo and exercise [17].

Do GLP-1 agonists have cardiovascular benefits?

If you have type 2 diabetes, you have an elevated risk of developing cardiovascular diseases, such as myocardial infarction or heart attack, heart failure, peripheral artery disease, stroke, and cardiovascular death [18-20]. Cardiovascular diseases are the most prevalent cause of morbidity and mortality among patients with type 2 diabetes [19, 20]. Globally, approximately 32% of people with type 2 diabetes are affected by cardiovascular diseases [21].

According to the American Diabetes Association recommendations, GLP-1 medications with demonstrated beneficial cardiovascular effects are dulaglutide, semaglutide, and liraglutide [5]. These three GLP-1 medications are also currently FDA-approved based on clinical studies to reduce cardiovascular risks in adults with type 2 diabetes [9-14]. Multiple large clinical trials report significant reductions in cardiovascular events in adults with type 2 diabetes [5,22]. A meta-analysis study of 8 clinical trials, including over 60,000 patients with a primary outcome of major adverse cardiovascular events, found an overall GLP-1 medication reduction rate of 14% [22]. Additional results of the meta-analysis showed GLP-1 medications reduced all-cause mortality by 12% and hospital admission for heart failure by 11% in type 2 adult patients. The meta-analysis reported several limitations since it included multiple studies.

Adverse reactions and potential safety issues of GLP-1 medications

GLP-1 RAs have a preferable safety profile in terms of improved weight loss and low risk for hypoglycemia [7]. However, GLP-1 medications also have different adverse reactions and contraindications. Common adverse reactions of GLP-1 medications are nausea, vomiting, and diarrhea [6]. Other adverse reactions include dizziness, mild tachycardia, infections, headaches, and dyspepsia. In longer-acting GLP-1 medications, injection-site pruritus and erythema are also common. Safety concerns include pancreatitis, thyroid cancer, and severe gastrointestinal issues, and GLP-1 medications should be avoided in people with a history of these conditions [7].

Key points

• Diabetes impacts about 37 million people in the United States, approximately 11.3% of the population
• Type 2 diabetes accounts for up to 95% of people with diabetes
• GLP-1 medications are also known as glucagon-like peptide-1 (GLP-1) agonists, GLP-1 receptor agonists, incretin memetics, or GLP-1 analogs
• GLP-1 medications lower blood sugars by binding and activating the GLP-1 receptors to enhance insulin secretion and synthesis from the pancreas by promoting beta cells, suppressing glucagon secretion, slowing gastric emptying, and reducing food intake by decreasing appetite
• GLP-1 medications used in combination with exercise can synergistically work together to lower blood sugar levels
• GLP-1 agonists, specifically dulaglutide, semaglutide, and liraglutide, have demonstrated cardiovascular reduction benefits based on large clinical trials

Virtual care and questions about GLP-1 medications

If you have type 2 diabetes and want to learn more about GLP-1 medications, consider speaking with a healthcare provider. Everlywell provides access to a virtual telehealth option for weight management online where you can schedule a meeting with a certified, licensed provider to discuss your health and GLP-1 medication. Everlywell also works with a network of labs to get you access to various tests. Learn more about Everlywell and what is available for you.

Related content

What are the GLP-1 drugs?

How does GLP-1 work for weight loss?

Do you need a prescription for GLP-1?

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References

1. What is diabetes? Centers for Disease Control and Prevention. URL. Published July 7, 2022. Accessed February 20, 2023.
2. National Diabetes Statistics Report. Centers for Disease Control and Prevention. URL. Published June 29, 2022. Accessed February 20, 2023.
3. Type 2 diabetes. Centers for Disease Control and Prevention. URL. Published December 30, 2022. Accessed February 20, 2023.
4. Type 2 diabetes. Mayo Clinic. URL. Published November 19, 2022. Accessed February 20, 2023.
5. ElSayed NA, Aleppo G, Aroda VR, et al. Pharmacologic approaches to glycemic treatment: standards of care in diabetes-2023. American Diabetes Association. URL. Published December 12, 2022. Accessed February 20, 2023.
6. Glucagon-like peptide-1 receptor agonists. NCBI BOOKSHELF. URL. Accessed February 20, 2023.
7. Sheahan KH, Wahlberg EA, Gilbert MP. An overview of GLP-1 agonists and recent cardiovascular outcomes trials. Postgrad Med J. 2020;96(1133):156-161. doi:10.1136/postgradmedj-2019-137186. URL.
8. Elsevier drug class overview: Glucagon-like peptide-1 (GLP-1) receptor agonists. Elsevier. URL. Accessed February 20, 2023.
9. DailyMed - trulicity- dulaglutide injection, solution. US National Library of Medicine. URL. Accessed February 20, 2023.
10. DailyMed - byetta- exenatide injection. US National Library of Medicine. URL. Accessed February 20, 2023.
11. DailyMed - Bydureon- exenatide injection, suspension, extended release bydureon- Exenatide Kit. US National Library of Medicine. URL. Accessed February 20, 2023.
12. DailyMed - victoza- liraglutide injection. U.S. National Library of Medicine. URL. Accessed February 20, 2023.
13. DailyMed - ADLYXIN- lixisenatide kit adlyxin- lixisenatide injection, solution. US National Library of Medicine. URL. Accessed February 20, 2023.
14. DailyMed - OZEMPIC- semaglutide injection, solution. U.S. National Library of Medicine. URL. Accessed February 20, 2023.
15. ElSayed NA, Aleppo G, Aroda VR, et al. Prevention or delay of type 2 diabetes and associated comorbidities: Standards of care in Diabetes-2023. American Diabetes Association. URL. Published December 12, 2022. Accessed February 20, 2023.
16. Hamasaki H. Exercise and glucagon-like peptide-1: Does exercise potentiate the effect of treatment? World J Diabetes. 2018;9(8):138-140. doi:10.4239/wjd.v9.i8.138. URL.
17. Mensberg P, Nyby S, Jørgensen PG, et al. Near-normalization of glycaemic control with glucagon-like peptide-1 receptor agonist treatment combined with exercise in patients with type 2 diabetes. Diabetes Obes Metab. 2017;19(2):172-180. doi:10.1111/dom.12797. URL.
18. Marx N, Husain M, Lehrke M, Verma S, Sattar N. GLP-1 receptor agonists for the reduction of atherosclerotic cardiovascular risk in patients with type 2 diabetes. Circulation. 2022;146(24):1882-1894. doi: 10.1161/CIRCULATIONAHA.122.059595. URL.
19. Matheus AS, Tannus LR, Cobas RA, Palma CC, Negrato CA, Gomes MB. Impact of diabetes on cardiovascular disease: an update. Int J Hypertens. 2013;2013:653789. doi:10.1155/2013/653789. URL.
20. Del Olmo-Garcia MI, Merino-Torres JF. GLP-1 receptor agonists and cardiovascular disease in patients with type 2 diabetes. J Diabetes Res. 2018;2018:4020492. doi:10.1155/2018/4020492. URL.
21. Einarson TR, Acs A, Ludwig C, Panton UH. Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007-2017. Cardiovasc Diabetol. 2018;17(1):83. doi:10.1186/s12933-018-0728-6. URL.
22. Sattar N, Lee MMY, Kristensen SL, et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol. 2021;9(10):653-662. doi:10.1016/S2213-8587(21)00203-5. URL.