Glucagon-like peptide-1 receptor agonists (GLP-1 agonists) is a class of antidiabetic medications that have become increasingly popular in the treatment of obesity. Treatment with GLP-1 drugs has been shown to improve glucose control and reduce hemoglobin A1C in individuals with diabetes. These medications also slow digestion, provide cardiovascular benefits and promote weight loss.
The first drug approved in this class was Byetta™ in 2005 which is dosed twice daily, every day. As products dosed once weekly became available and research demonstrated weight loss and cardiovascular benefits, competitors such as as Ozempic®, Trulicity®, Wegovy®, Saxenda® and Mounjaro™ have gained attention, with a notable increase in demand in recent years. Common side effects reported with this drug class include constipation, bloating and indigestion. Typically, higher doses result in the greatest glucose control and weight loss but may also lead to a more notable side-effect experience. As a result, patients are started on a low dose and are slowly titrated up to the highest available dose they can tolerate. Patients are advised to follow their prescribed dosing schedule and check in with their provider with any questions or concerns.
With growing popularity, several safety and availability concerns have arisen regarding the GLP-1 drugs. In September 2023, the FDA updated Ozempic®’s label to include a warning of intestinal blockage, known as ileus. This warning already existed on the labels for Wegovy® and Mounjaro™. Ileus is a rare but potentially serious side effect. To date, there have been 33 reported cases of ileus and 2 deaths thought to be caused by the use of a GLP-1 drug. Due to the risk of developing ileus, it is important for a patient’s medical history to be reviewed prior to initiation of a GLP-1 drug to determine if the potential benefits of a GLP-1 agonist outweigh the associated risks.
As newer GLP-1 products have seen a rise in off-label utilization for weight loss without type-2 diabetes, there has been a recent increase in demand and industry-wide shortages, reducing access for some patients with diabetes. This can create a barrier to medication adherence for these patients and interfere with their dosing escalation schedule. Others have also expressed a reluctance to begin a GLP-1 medication because they do not want to be affected by these shortages. Diabetic patients should be informed that alternative GLP-1 drug options are available should a patient choose to switch to a different medication or if their current medication is not available. Manufacturers have taken note of this and are working to increase supplies available to meet demand. Recently, on November 2, 2023, Eli Lilly announced their expansion to increase Mounjaro™ supply and availability. Inventory at wholesalers in the United States has improved, and all six strengths are currently available. Mounjaro™ is only approved for the treatment of diabetes, but Eli Lilly has just received FDA approval for Zepbound™, a product that contains the same active ingredient and is indicated for weight loss. Eli Lilly recognizes that this additional product and indication will lead to a significant increase in demand and are working to provide a sufficient supply of both medications following this approval.