Obesity is a chronic disease and a global health challenge across all ages and socioeconomic backgrounds. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), has shown promising results for obesity management.
Initially, an injectable form of this medication was introduced under the name Ozempic to treat type 2 diabetes mellitus (T2DM). This was followed by the approval of the first oral GLP-1 RA, known as Rybelsus, by the U.S. Food and Drug Administration (FDA) in 2019. Subsequently, in 2021, the FDA approved the use of this medication for weight loss under the name Wegovy.1 Another GLP-1 RA called tirzepatide received FDA approval in 2023. In addition to GLP-1, tirzepatide also activates another hormone receptor called glucose-dependent insulinotropic polypeptide or GIP. Tirzepatide is available under the proprietary names Mounjaro for T2DM and Zepbound for weight loss.
Apart from treating T2DM, semaglutide is also approved for managing chronic obesity in patients with a BMI greater than 30, or with a BMI higher than 27 and comorbidities such as hypertension, dyslipidemia, or diabetes mellitus. Semaglutide has demonstrated significant efficacy compared to both placebos and other GLP-1 receptor agonists, like liraglutide, in multiple randomized trials, sparking interest among physicians in prescribing semaglutide.2
While semaglutide and similar GLP-1 RA are primarily used in outpatient settings and not on most hospitals’ formularies, hospitalists should familiarize themselves with its uses and adverse effects.
GLP-1 RAs have several positive effects on the body. They increase insulin secretion, reduce the release of glucagon, inhibit the production of glucose by the liver, and improve insulin sensitivity. One of their most important effects is slowing down the movement of food in the stomach and sending signals of fullness to the brain, which helps patients feel full after eating a small meal and reduces their overall calorie intake.
GLP-1 RAs are usually prescribed by endocrinologists, obesity medicine specialists, and primary care physicians (PCPs). However, with increased evidence of these drugs reducing cardiovascular mortality in patients with T2DM and a recent randomized controlled trial showing improved symptoms (compared to placebo) in patients with heart failure with preserved ejection fraction and obesity, semaglutide is being prescribed by cardiologists as well.3
Many weight-loss clinics and medical spas also dispense a compounded formulation of semaglutide which is not produced by the original manufacturer. Patients may choose this option because prescription semaglutide is not covered by their insurance. The FDA allows compounders to prepare a compounded version of a drug if it is in short supply, and injectable semaglutide was in short supply for most of 2023. However, the FDA does not review compounded versions of these drugs for safety, quality, or effectiveness.1 Similarly, patients may be obtaining semaglutide online with absolutely no checks and these sources may have too little, too much, or no active drug at all.
As with any GLP-1 RA, major adverse effects of semaglutide include nausea, vomiting, diarrhea, and constipation. Some less common side effects are pancreatitis, bowel obstruction, and gastroparesis. Given the popularity of GLP-1 RAs, it’s essential for hospital staff to conduct a comprehensive medication reconciliation and history for patients who present with the mentioned complaints. This is particularly important because patients may have been prescribed semaglutide from medical spas or other sources not linked to their electronic health records (EHRs).
For patients presenting with nausea, vomiting, or constipation, these adverse effects are self-limiting, and holding the GLP-1 RA, hydration with IV fluids, and bowel rest should be enough for most patients. Hence, extensive diagnostic testing in the form of endoscopies and imaging studies should be avoided for these patients.
Patients presenting with acute pancreatitis should be managed on the same lines as you would manage pancreatitis. Semaglutide is, however, contraindicated in patients with acute pancreatitis, and it should not be resumed after discharge.3
There have been reports of increased risk of aspiration pneumonia during anesthesia in patients taking semaglutide. This is due to delayed gastric emptying and since semaglutide has a long half-life, the American Society of Anesthesiologists recommends holding semaglutide for one week prior to elective procedures.4 For semi-urgent or urgent procedures, you should share the concern of a possible full stomach with the patient, anesthesiologist, and surgeon or proceduralist so they can be appropriately prepared during the surgery. Also, semaglutide should not be prescribed or discontinued in patients with advanced diabetic gastroparesis, history of bowel obstruction, or severe constipation.
It is imperative to educate patients about the chronicity of obesity and that semaglutide is not a quick fix. The STEP 1 Extension trial showed that one year after stopping semaglutide and lifestyle intervention, the patients regained a mean of two-thirds of their initial weight loss. The same randomized controlled trial revealed that improvement in cardiometabolic profile also started to diminish after one year of holding semaglutide.5
The initiation of GLP-1 agonists like semaglutide in the acute inpatient setting for weight loss is uncommon. Use by the hospitalist for the management of T2DM-related hyperglycemia is more likely, either as continuation of outpatient therapy, or initiated near discharge as part of a transition management plan if the patient is eating, has no contraindications to initiation or continuation of therapy, and glucose levels are well controlled.
However, routine use during an acute hospitalization is uncommon, owing to issues around the availability of formulary, cost to the system, lack of widespread insurance coverage, and availability. Further, national guidelines such as those from the Endocrine Society recommending the use of insulin therapy rather than non-insulin therapies for glycemic management may also limit its routine use in the acute setting.6 Hospitalists are more likely to encounter such drugs in individuals already receiving them in the ambulatory arena who present with an acute issue, highlighting the importance of understanding its side effect profile.
Key Points
- Hospitalists should be aware of semaglutide’s minor side effects like abdominal pain, constipation, nausea, and vomiting, and its major side effects like bowel obstruction and pancreatitis.
- It is crucial to perform a thorough medication reconciliation and be aware that patients may be taking medications in the compounded form which may not show on the EHR.
- Hospitalists should educate themselves about this medication class so they can counsel patients about considering GLP-1RAs and referring them to their PCPs or endocrinologists.
Dr. Singh
Dr. Mgbojikwe
Dr. Adhikari
Dr. Modha
Dr. Singh is a hospitalist and associate staff in the department of hospital medicine at Cleveland Clinic Community Care in Mayfield Heights, Ohio. Dr. Mgbojikwe is an associate chief medical officer, associate professor, and hospitalist at Fox Chase Cancer Center in Philadelphia. Dr. Adhikari is a hospitalist with the Franciscan Alliance in Lafayette, Ind. Dr. Modha is a staff physician in the department of hospital medicine at the Cleveland Clinic, and an assistant professor of medicine at Cleveland Clinic Lerner College of Medicine of Case Western Reserve University of Medicine in Cleveland.
References
- U.S. Food & Drug Administration. Medications containing semaglutide marketed for type 2 diabetes or weight loss. FDA website. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/medications-containing-semaglutide-marketed-type-2-diabetes-or-weight-loss. Published January 10, 2024. Accessed July 5, 2024.
- Phillips A, Clements JN. Clinical review of subcutaneous semaglutide for obesity. J Clin Pharm Ther. 2022;47(2):184-93.
- Kosiborod MN, Abildstrøm SZ, et al. Semaglutide in patients with heart failure with preserved ejection fraction and obesity. N Engl J Med. 2023;389(12):1069-84.
- Joshi GP, Abdelmalak BB, et al. American Society of Anesthesiologists consensus-based guidance on preoperative management of patients (adults and children) on glucagon-like peptide-1 (GLP-1) receptor agonists. American Society of Anesthesiologists website. https://www.asahq.org/about-asa/newsroom/news-releases/2023/06/american-society-of-anesthesiologists-consensus-based-guidance-on-preoperative. Published June 29, 2024. Accessed July 5, 2024.
- Wilding JPH, Batterham RL, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-64.
- Korytkowski MT, Muniyappa R, et al. Inpatient hyperglycemia guideline resources. Endocrine Society website. https://www.endocrine.org/clinical-practice-guidelines/inpatient-hyperglycemia-guideline-resources. Published June 12, 2022. Accessed July 5, 2024.