The recent uptick of prescribing glucagon-like peptide 1 (GLP-1) agonists has created market shortages due to unprecedented demands. Liraglutide, dulaglutide, tirzepatide and semaglutide are indicated to improve glycemic control in type 2 diabetes mellitus. In addition, tirzepatide and semaglutide have separate indications under different trade names for chronic weight management for qualifying individuals. Tirzepatide differs from the others in that it has an additional mechanism of action as a glucose-dependent insulinotropic polypeptide (GIP) receptor agonist. This does not differ the side effect profile significantly, so the following monitoring recommendations still apply. Manufacturers expect shortages throughout 2024, but demand and prescribing trends show no signs of slowing. With the rising popularity off these agents, it is important that health care professionals and patients be aware of monitoring parameters and potential adverse effects. While generally well tolerated, there are minor and severe side effects to be aware of and proactively monitor. Injection site reactions, hypoglycemia, acute kidney injury, pancreatitis, and worsening diabetic retinopathy are potential complications.
GLP-1 agonists are injected subcutaneously. As with all injections, this comes with potential for injection site reactions including rash and erythema. Supportive care is usually sufficient and rotating injection sites can lessen discomfort. Hypoglycemia, a common diabetic problem, can be exacerbated in some populations. Close blood glucose monitoring is particularly necessary when a patient is treated with a GLP-1 agonist in combination with a sulfonylurea or insulin. Blood glucose monitoring is patient specific and should be tailored to their individual situation. Considering their concurrent medications and blood glucose trends can determine the frequency of daily readings needed. Hemoglobin A1C is recommended twice yearly in stable patients who meet their treatment goals. For patients with dose changes and not yet reaching treatment goals more frequent HbA1C monitoring is suggested quarterly.
Renal function and pancreatitis are always of concern in diabetic population, and this class of medication is no exception. Baseline renal function upon initiation and with dose changes is recommended. Acute kidney injury was not clinically linked to previous underlying kidney disease, but was often correlated with nausea, vomiting, diarrhea, and dehydration. Pancreatitis and acute gallbladder disease have no preventive monitoring recommendations for this class of medications. Any concerning signs of pancreatitis or cholelithiasis in a patient such as severe abdominal pain should be investigated with further workup.
Along with kidney and pancreatic function, eye health is a top priority in patients with diabetes. Diabetic retinopathy was found at clinical trials at increased incidence compared to placebo. However, the risk for retinopathy complications was correlated with a baseline diagnosis of diabetic retinopathy. Thus, appropriate monitoring with eye exams is indicated for patients with a prior history of diabetic retinopathy. ADA guidelines already recommend yearly eye exams for diabetic patients as part of their standard of care, so for most patients this will not constitute a change.
Perhaps the most concerning finding of the clinical trials was the increase in incidence of thyroid c-cell tumors at clinical doses of GLP-1 agonists in mice and rats. Human correlation has not been determined. Of note, this class of medications is contraindicated in individuals with a family history of medullary thyroid carcinoma. History of papillary, follicular, and anaplastic thyroid cancer does not constitute a contraindication. At this time, routine monitoring of serum calcitonin and thyroid imagine is not recommended. Further evaluation is warranted if nodules are detected on a patient.
Glucagon-like peptide 1 agonists are a popular and effective class of medication for improving glycemic control in patients with type 2 diabetes or as an adjunct for weight loss in qualifying populations, depending on the product specific indication approval. Many patients will have success reaching their glucose and weight goals, but health care professionals must be vigilant in the necessary patient monitoring. While many of the recommended monitoring parameters are already part of the standard of care for a patient with diabetes, this will be new ground for patients without diabetes using GLP-1 for weight loss. As new data is collected with the increased prescribing of this class of medications, we will be sure to see updated monitoring recommendations and guidelines.
