From the Guidelines
GLP-1 medications do not cause high insulin levels; instead, they help regulate insulin in a glucose-dependent manner. These medications, including semaglutide, liraglutide, dulaglutide, and tirzepatide, work by stimulating insulin release only when blood glucose levels are elevated, as noted in the 2024 standards of care in diabetes 1. This means they trigger insulin production when you need it after eating, but don't cause insulin spikes when blood sugar is normal.
Key Points
- GLP-1 medications stimulate insulin secretion and reduce glucagon secretion in a glucose-dependent manner, improving satiety and promoting weight loss, as reported in the 2018 consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) 1.
- They have minimal risk for hypoglycemia, but may increase the hypoglycemic potential of insulin and sulfonylureas when combined with those medications, as stated in the 2020 KDIGO clinical practice guideline for diabetes management in chronic kidney disease 1.
- GLP-1 medications actually help prevent hypoglycemia (low blood sugar) because they stop stimulating insulin when glucose levels normalize.
- They also slow gastric emptying, reduce glucagon secretion (a hormone that raises blood sugar), and promote satiety, which helps with weight management, as discussed in the 2024 standards of care in diabetes 1.
Benefits
- Improve blood sugar control without the risk of insulin-induced hypoglycemia that can occur with some other diabetes medications.
- Have additional benefits over insulin and sulfonylureas, specifically lower risk for hypoglycemia and favorable weight, cardiovascular, and kidney endpoints, as noted in the 2024 standards of care in diabetes 1.
From the FDA Drug Label
Exenatide is a GLP-1 receptor agonist that enhances glucose-dependent insulin secretion by the pancreatic beta-cell, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying. Exenatide has acute effects on pancreatic beta-cell responsiveness to glucose leading to insulin release predominantly in the presence of elevated glucose concentrations.
GLP medications, such as exenatide, enhance glucose-dependent insulin secretion. This means that they increase insulin levels, but only when glucose levels are elevated.
- Key points:
- GLP medications increase insulin secretion in response to high glucose levels
- Insulin secretion subsides as blood glucose concentrations decrease and approach euglycemia
- GLP medications do not impair the normal glucagon response to hypoglycemia 2
- GLP medications, such as liraglutide, have been shown to have similar effects on glucose-dependent insulin secretion 3
From the Research
GLP-1 Medications and Insulin Levels
- GLP-1 receptor agonists have been shown to enhance insulin release and reduce glucagon release in a glucose-dependent manner, which leads to improved glycemic control with a low risk of hypoglycemia 4, 5.
- The mechanism of action of GLP-1RAs involves activating GLP-1 receptors in the pancreas, which leads to increased insulin secretion and decreased glucagon secretion 5, 6.
- GLP-1RAs have been found to improve glycemic parameters, reduce body weight, and have a low risk of hypoglycemia, making them a useful tool for managing type 2 diabetes 4, 7, 5, 6.
- The effects of GLP-1RAs on insulin levels are glucose-dependent, meaning that they only increase insulin secretion when glucose levels are high, which reduces the risk of hypoglycemia 5, 6.
Comparison of GLP-1RAs
- Short-acting GLP-1RAs (exenatide and liraglutide) offer improved coverage of postprandial hyperglycemia, while longer-acting GLP-1RA formulations (exenatide extended-release, dulaglutide, and albiglutide) further improve fasting plasma glucose 7, 6.
- Reductions in body weight and blood pressure appear similar among individual GLP-1RA agents, and small increases in heart rate are of unknown clinical relevance 6.
- Gastrointestinal adverse events are less frequent with longer-acting GLP-1RAs, and hypoglycemia incidence is low but increased when GLP-1RAs are used with insulin secretagogues or insulin 7, 6.
Clinical Use of GLP-1RAs
- GLP-1RAs are recommended as a preferred add-on agent to existing metformin monotherapy, as first-line therapy if metformin is contraindicated or poorly tolerated, and for use in combination with other oral glucose-lowering agents or basal insulin 7, 6.
- Selection of the most appropriate GLP-1RA treatment for individual patients is important, taking into account clinical characteristics, therapeutic goals, and patient preference 7, 8.