Incretins for blood sugar control and management
The term "incretin" to describe gut-stimulated
hormones that communicate with
the pancreas was proposed well before these hormones were ultimately isolated.1
These incretin hormones, known as glucose-dependent insulinotropic polypeptide (GIP)
and GLP-1, are released with food intake and play an essential role in
stimulating the pancreatic ß cell to provide insulin for glucose metabolism.2 So
far, GLP-1 has proven to be a better target for drug development than GIP,
primarily because GLP-1, unlike GIP, suppresses meal-stimulated elevations of
glucagon, which has also been shown to improve appetite control. Within minutes
of food reaching the gut, GLP-1 is secreted by L cells within the ileum and
colon, rapidly signaling the beta cell. In addition to its role in stimulating
insulin release, GLP-1 has been associated with regulating gastric emptying and
promoting ß-cell proliferation and neogenesis.
In type 2 diabetes mellitus, two new classes of drugs have been developed that
affect signaling between the gut and the pancreatic ß cell. One drug from each
of these classes, dipeptidyl peptidase IV (DPP-IV) inhibitors and glucagon-like
peptide-1 (GLP-1) mimetics, are now available for clinical use.
After hospitalization
Post hospital discharge management of diabetic patients is a challenge because
of the availability of a wide variety of oral antidiabetes agents, including
metformin, sulfonylureas, and thiazolidinediones, each with distinct therapeutic
and adverse event profiles. Incretin-based therapies offer a potentially useful
option for post-discharge therapy, and possibly for inpatient diabetes
treatment. Incretins thus far appear to be well-tolerated; they are easier for
patients to use compared with insulin injections (eg, continual glucose
monitoring is not required); and they may provide long-term improvement of
cardiovascular parameters and beta-cell function.
The Incretin Effect in Diabetic control
DPP-IV inhibitors and GLP-1 mimetics act on a novel therapeutic target. Both
affect the activity of incretin hormones, which communicate between the gut and
the ß cell.