From the Guidelines
DPP-4 inhibitors are associated with a low risk of hypoglycemia and augment insulin secretion, but are less effective than metformin for lowering HbA1c and do not promote significant weight loss. The mechanism of action of DPP-4 inhibitors involves inhibiting the enzyme dipeptidyl peptidase-4, which breaks down incretin hormones like GLP-1 and GIP, thereby enhancing glucose-dependent insulin secretion from pancreatic beta cells and suppressing glucagon release from alpha cells 1. According to the most recent evidence, DPP-4 inhibitors are generally weight-neutral rather than promoting weight loss, and they primarily affect insulin secretion rather than insulin resistance 1. Some key points about DPP-4 inhibitors include:
- They do not increase the risk for hypoglycemia when used as monotherapy or with other agents that don't independently cause hypoglycemia 1
- They are less effective than metformin at lowering HbA1c, typically reducing it by 0.5-0.8% compared to metformin's 1-1.5% reduction 1
- They are generally well-tolerated and effective for glycaemic control in patients with mild-to-moderate hyperglycaemia 1
- Their glucose-dependent mechanism of action means they stimulate insulin only when blood glucose is elevated, explaining their low risk of hypoglycemia when used as monotherapy or with other agents that don't independently cause hypoglycemia 1. Overall, DPP-4 inhibitors are a useful treatment option for patients with type 2 diabetes, particularly those who are at risk for hypoglycemia or have renal impairment, but metformin remains the first-line therapy due to its efficacy and safety profile 1.
From the FDA Drug Label
Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the DPP-4 enzyme within minutes GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production. In patients with type 2 diabetes mellitus, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved Saxagliptin is a competitive DPP-4 inhibitor that slows the inactivation of the incretin hormones, thereby increasing their bloodstream concentrations and reducing fasting and postprandial glucose concentrations in a glucose-dependent manner in patients with type 2 diabetes mellitus. In patients with type 2 diabetes mellitus, administration of saxagliptin inhibits DPP-4 enzyme activity for a 24-hour period. After an oral glucose load or a meal, this DPP-4 inhibition resulted in a 2- to 3-fold increase in circulating levels of active GLP-1 and GIP, decreased glucagon concentrations, and increased glucose-dependent insulin secretion from pancreatic beta cells
The correct answer is:
- they augment insulin secretion: DPP-4 inhibitors increase glucose-dependent insulin secretion from pancreatic beta cells.
- they do not increase the risk for hypoglycemia: Although the label does not explicitly state this, DPP-4 inhibitors are known to have a low risk of hypoglycemia due to their glucose-dependent mechanism of action. The other options are not supported by the provided text. 2
From the Research
DPP-4 Inhibitors Characteristics
- They are associated with a low risk of hypoglycemia 3, 4, 5, 6
- They do not increase the risk for hypoglycemia 3, 4, 5, 6
- They are weight neutral, meaning they do not cause significant weight gain or loss 3, 4, 7, 5
- They augment insulin secretion by increasing the active levels of incretin hormones in the body 4, 5, 6
- They reduce glucagon secretion, thereby lowering glucose levels 4, 5, 6
Comparison with Metformin
- DPP-4 inhibitors are less effective than metformin for lowering HbA1c 3, 7
- They have a similar glucose-lowering effect as metformin, but with better gastrointestinal tolerability 3