Understanding Ozempic

“Ask your doctor if Ozempic is right for you”

In the past 24 hours, I have seen Ozempic on TV commercials, advertised behind home plate at a baseball game, on a billboard for medically supervised weight loss, and in pop-culture articles following new celebrity trends. It seems like overnight, Ozempic is everywhere, and it represents only one brand name of several available versions of the generic drug semaglutide.

What is semaglutide? Who takes semaglutide? How could it impact your patient care? Let’s examine the facts.

What is semaglutide?

Semaglutide is commonly referred to as an incretin based therapy. Incretin hormones, GIP and GLP-1, are released when nutrients (especially glucose and starches) meet special cells in the intestine as food clears the stomach. The job of incretin hormones is to communicate with the pancreas, to help regulate the release of insulin and glucagon [1].

Semaglutide is a GLP-1 receptor agonist (GLP-1 RA). Stimulating this receptor increases the release of insulin and inhibits the release of glucagon, leading to decreases in blood glucose [2]. Semaglutide is also believed to stimulate GLP-1 receptors in the brain (hypothalamus) which decreases appetite. This, combined with its ability to delay gastric emptying, can lead to beneficial effects on body weight. It is typically administered subcutaneously, with a time-to-peak onset of 24 hours and a half-life of 5.7 to 6.7 days [2].

FDA-approved semaglutide products

Who takes semaglutide

There are currently three general indications for GLP-1 RAs:

1. Glycemic management in patients with type 2 diabetes
2. Reducing the risk of major adverse cardiovascular events in patients with type 2 diabetes
3. As a weight loss aid for patients who are obese or overweight with cardiovascular risk factors

Semaglutide is one of a number of GLP-1 RAs recommended in the management of type 2 diabetes. Typically, this class of drug is considered when blood glucose control is inadequate with metformin [3]. Semaglutide is recommended ahead of other GLP-1 RAs (such as dulaglutide and tirezpatide) for its very high efficacy in lowering blood sugars. Semaglutide is typically administered subcutaneously on a weekly basis; however, a once-daily oral form has also been approved [4].

The management of diabetes complications has typically been guided by the three pillars of managing blood sugar, blood pressure and cholesterol. A fourth pillar, agents with cardiovascular and kidney benefit, has recently been added [5]. GLP-1 RAs are generally more effective in thrombotic events; however, other drugs appear more effective in treating heart failure and kidney failure [6]. The SUSTAIN-6 trial demonstrated reductions in both non-fatal MI and CVA [7]. One theory is that GLP-1 may have anti-inflammatory properties, and may lead to less plaque development and more stable plaques. The drug is also associated with a mild decrease in blood pressure [2]. This means semaglutide may be administrated to patients with history of atherosclerotic cardiovascular disease, even if their blood glucose is well controlled [2,5].

In 2021, the FDA approved the semaglutide formulation Wegovy for weight loss, based largely on the STEP trial that demonstrated a 12.4% average loss in body weight over the course of a year [8-9]. It is administered weekly by subcutaneous injection, starting at 0.25 mg and increasing monthly to a maximum of 2.4 mg, to minimize the adverse effects on the GI system reported by 73% of patients [10]. As discussed, GLP-1 decreases appetite and makes patients feel full longer, which leads to weight loss. Additionally, it is theorized that obesity may cause a decrease in the normal secretion of GLP-1 with eating, leading to an increase in the beneficial effects of semaglutide on body weight [1].

Prehospital considerations

There are three things to consider in patients taking semaglutide:

1. Check the blood sugar. In patients taking semaglutide alone, the risk of hypoglycemia is relatively low (0-3.8%). The risk of hypoglycemia increases as the dose increases, and increases again when dual therapy is being used. Hypoglycemia occurred most often in patients taking 1 mg of Ozempic with sulfonylurea (24.4%) or with insulin (29.8%) (11).
2. Don’t ignore GI symptoms. Some of the most common side effects to semaglutide are GI symptoms. Nausea (16-20%), vomiting (5-9%), diarrhea (7-6%), abdominal pain (9%) and constipation (3-5%) have all been reported and tend to be dose dependent [11]. Most of these can be considered mild and transient, and are typically managed with medications like proton pump inhibitors as well as counseling patients on changing behaviors (e.g., eating smaller meals more often, avoiding spicy food) [2]. However, there have been reports of pancreatitis (including fatalities) associated with semaglutide use. Patients with severe abdominal pain, pain which radiates to the back, with or without vomiting should be assessed for pancreatitis [11].
3. Check the drug label. There are relatively few examples of semaglutide overdose; however, recently, a number of unintentional dosing errors occurred when the drug provided did not come from the manufacturer. In two cases, the drug was obtained from a mail order pharmacy, and one received the drug in an aesthetic spa. Symptoms were generally related to nausea, vomiting and decreased intake lasting for a few days, with some including weakness, abdominal pain or diarrhea. All of the cases resolved with fluid and anti-emetics [12]. This, combined with the drug shortages and increasing public attention, has prompted an FDA warning about the risks of obtaining compounded versions of semaglutide which may contain untested versions of the drug or other inappropriate additives [13]. No generic form of semaglutide has been approved, so this possibility should be considered if the drug did not come from a licensed pharmacy or was not administered in the pen provided by the manufacturer.

References

1. Nauck MA, Meier JJ. Incretin hormones: Their role in health and disease. Diabetes Obes Metab. 2018;20 Suppl 1:5-21. doi:10.1111/dom.13129
2. 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
3. ElSayed NA, Aleppo G, Aroda VR, et al. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes-2023. Diabetes Care. 2023;46(Suppl 1):S140-S157. doi:10.2337/dc23-S009
4. United States Food and Drug Administration. FDA approves first oral GLP-1 treatment for type 2 diabetes. September 20, 2019.
5. ElSayed NA, Aleppo G, Aroda VR, et al. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2023 [published correction appears in Diabetes Care. 2023 Jan 26;:]. Diabetes Care. 2023;46(Suppl 1):S158-S190. doi:10.2337/dc23-S010
6. ElSayed NA, Aleppo G, Aroda VR, et al. 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes-2023. Diabetes Care. 2023;46(Suppl 1):S191-S202. doi:10.2337/dc23-S011
7. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, Lingvay I, Rosenstock J, Seufert J, Warren ML, Woo V, Hansen O, Holst AG, Pettersson J, Vilsbøll T; SUSTAIN-6 Investigators. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016 Nov 10;375(19):1834-1844. doi: 10.1056/NEJMoa1607141. Epub 2016 Sep 15. PMID: 27633186.
8. United States Food and Drug Administration. FDA approves new drug treatment for chronic weight management, first since 2014. June 04, 2021
9. 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):989-1002. doi: 10.1056/NEJMoa2032183. Epub 2021 Feb 10. PMID: 33567185.
10. Wegovy (semaglutide) for injection: Full prescribing information. NovoNordic Inc (Revised 06/2021).
11. Ozempic (semaglutide) for injection: Full prescribing information. NovoNordic Inc (Revised 03/2023).
12. Lambson JE, Flegal SC, Johnson AR. Administration errors of compounded semaglutide reported to a poison control center-Case series. J Am Pharm Assoc (2003). 2023 Jun 29:S1544-3191(23)00231-5. doi: 10.1016/j.japh.2023.06.017. Epub ahead of print. PMID: 37392810.
13. United States Food and Drug Administration. Medications Containing Semaglutide Marketed for Type 2 Diabetes or Weight Loss 05/31/2023