GLP-1 agonist · type 2 diabetes
An injectable drug for type 2 diabetes, lixisenatide belongs to the GLP-1 receptor agonist class. It mimics GLP-1, a gut hormone that helps control blood sugar after meals. In the US it was approved both on its own (Adlyxin) and in a fixed combination with the long-acting insulin glargine (Soliqua).
Like natural GLP-1, lixisenatide activates GLP-1 receptors. This increases insulin release in a glucose-dependent way, meaning more insulin when blood sugar is high, and reduces glucagon, the hormone that tells the liver to release sugar1. It also slows stomach emptying, which blunts the rise in blood sugar after a meal1. That same slowing can delay absorption of oral medicines taken around the same time, which is why the Soliqua label advises spacing certain drugs, such as oral contraceptives, some antibiotics and acetaminophen, relative to it1.
In Soliqua, it is paired with a basal insulin that lowers glucose by moving it into muscle and fat and by curbing sugar output from the liver1.
In ELIXA, 6,068 people with type 2 diabetes and a recent heart attack or hospitalization for unstable angina were randomized to lixisenatide or placebo and followed for a median of 25 months. Major cardiovascular events occurred at nearly identical rates (13.4% vs 13.2%): the drug did not significantly change cardiovascular risk. Heart-failure hospitalization, deaths, severe hypoglycemia, pancreatitis and serious adverse events were also similar to placebo3. Beyond diabetes, and after neuroprotective signals in a mouse model, the Phase 2 LIXIPARK trial gave lixisenatide or placebo to 156 people with early Parkinson's disease for 12 months. Motor scores held steady on the drug and worsened by about three points on placebo; the authors said longer and larger trials are needed. Nausea affected 46% and vomiting 13% of those on lixisenatide4.
The FDA approved lixisenatide in 2016, as Adlyxin and as Soliqua (with insulin glargine), to improve blood-sugar control in adults with type 2 diabetes alongside diet and exercise1,2. It is not approved for weight loss or for Parkinson's disease.
In the Soliqua label, the most common side effects are low blood sugar, nausea, diarrhea, headache, and nose, throat and upper-airway infections. Warnings include anaphylaxis and other serious allergic reactions (reported in lixisenatide trials), pancreatitis, severe digestive reactions, kidney injury from fluid loss, antibodies that can weaken blood-sugar control, gallbladder disease and aspiration under anesthesia. Insulin-related warnings include overdose from mix-ups between insulin products and low potassium1.
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