Dear Dr. Roach: In your recent column, you addressed a situation concerning insulin resistance, including weight gain. You mention that although there are drugs that work directly with insulin resistance, drugs in the glucagon-like peptide-1 agonist class (such as liraglutide and semaglutide) reduce risk of heart disease, promote weight loss and protect against serious complications. However, after investigating these two drugs, I found many side effects and warnings. Could you please address this?
S.T.
In Type 2 diabetes, GLP-1 treatments (including GLP-1 agonists like semaglutide and liraglutide, but also dual-acting GLP-1 and GIP agents like tirzepatide) have several benefits as well as some downsides. In many patients, the benefits outweigh the potential harms.
Heart disease remains a critical issue in men and women with diabetes. Both semaglutide and liraglutide injections showed improvements not only in diabetes control (they reduce the A1C test, a marker for blood sugar, by 1 to 1.5 percentage points), but in death due to heart disease and in death due to any cause, compared to a placebo treatment.
Since keeping our patients alive and free from heart disease are major goals, this is a very strong reason to prescribe these types of drugs in people at high risk for heart disease. Unlike some other types of medicines for diabetes, such as the thiazolidinediones (TZDs, which work more directly on insulin resistance than the GLP-1 agonists), liraglutide and semaglutide does not increase heart failure. Weight loss is common with GLP-1 agonists, but to me, that side effect is much less important than the beneficial effects on heart disease and overall mortality that the medicine can provide.
Nausea, vomiting and diarrhea are common side effects, but these can usually be managed by slowly increasing the dosages. Pancreatitis has been reported, so I do not use these medicines in a person with a history of pancreatitis. Further, gallbladder attacks are reported more frequently with this class of drugs, but many medicines that causes rapid weight loss may sometimes cause gallstone attacks. It is unclear whether kidney damage is more common. Kidney function should be monitored.
GLP-1 agonists are a valuable class of agents, particularly in people at high risk for heart disease who have not gotten good diabetes control with other treatments. The first-line treatment remains a healthy diet (your registered dietitian or nutritionist is a great resource for dietary advice) and regular exercise. If medication is needed, metformin remains the preferred initial treatment for most people with Type 2 diabetes who are overweight.
Dr. Roach regrets that he is unable to answer individual letters, but will incorporate them in the column whenever possible. Readers may email questions to [email protected]
