New study reassesses long-term safety and efficacy of GLP-1 agonists in type 2 diabetes

A new review of evidence, published in the Diabetes, Metabolic Syndrome and Obesity Dove Press journal, has looked at the long-term management of type 2 diabetes with different glucagon-like peptide-1 (GLP-1) receptor agonists.
GLP-1 receptor agonists (GLP1-RAs) are part of a novel class of blood sugar-lowering medications. They work by helping to increase insulin secretion and inhibit the release of glucagon in order to lower post-meal blood sugar levels.
They are generally prescribed to patients with or without insulin after other oral treatments, such as metformin or sulphonylureas, have failed.
The review pooled together findings from the latest long-term (a year-and-a-half long and over) phase 3 controlled and uncontrolled studies conducted on a number of GLP-1RAs approved in the US and the EU.
These include Eperzan (albiglutide), Trulicity (dulaglutide), Byetta (exenatide twice daily), Bydureon (exenatide once weekly), Victoza (liraglutide) and Lyxumia (lixisenatide).
Available data showed efficacy and tolerability for up to three years of treatment with many of them. But, how GLP-1RAs fare after the three-year mark was largely unknown.
According to the new findings, the longest study to date suggests Bydureon leads to continuous HbA1c reductions and weight loss over a seven-year period. Only minor cases of hypoglycemia were reported due to concomittant use of a sulphonylurea.
Eperzan leads to a modest reduction in HbA1c and weight after two years and has been associated with possible cases of pancreatitis.
Low- and high-dose Trulicity effectively reduced HbA1c and body weight in a two-year study comparing it to the dipeptidyl peptidase-4 (DPP-4) inhibitor Januvia (sitagliptin). However, cases of severe hypoglycemia occurred and one participant died of stroke.
Byetta was found to be superior to the sulphonylurea Amaryl (glimepiride) in four-year data and provides greater weight loss results than most other GLP-1 in less than two years. A high incidence of mild hypoglycemia was however reported.
Available data on Victoza mostly come from mid-term studies showing significant HbA1c reductions and weight loss results after two years, but a propensity to cause major hypoglycemic events or chronic pancreatitis, which resulted in the death of a patient.
Finally, Lyxumia allows satisfying blood glucose control for patients uncontrolled on metformin after a year and a half of treatment with little to no adverse events related to hypoglycemia or pancreatitis, compared to other GLP-1RAs.
Overall, research on long-term implications of GLP-1RAs is insufficient to conclusively say that they can be durably tolerated. Studies comparing various GLP-1RAs head-to-head for cardiovascular outcomes are especially lacking.