808
U N I T 9
Endocrine System
impaired hepatic and renal function who are taking the
longer-acting sulfonylureas.
The meglitinides (repaglinide) and related drugs (nat-
eglinide) are shorter-acting insulin secretagogues (termed
glinides) that target post-prandial glucose elevation.
These agents, which are rapidly absorbed from the gas-
trointestinal tract, are taken shortly before meals. Both
drugs can produce hypoglycemia; thus, proper timing
of meals in relation to drug administration is essential.
Biguanides.
Metformin, the only currently available
biguanide, inhibits hepatic glucose production and
increases the sensitivity of peripheral tissues to the
actions of insulin. Secondary benefits of metformin
therapy include weight loss and improved lipid profiles.
This medication does not stimulate insulin secretion;
therefore, it does not produce hypoglycemia. However,
it confers an increased risk for lactic acidosis, and is
contraindicated in people with elevated serum creati-
nine levels, clinical and laboratory evidence of severe
liver disease, or conditions associated with hypoxemia
or dehydration.
32
α
-Glucosidase Inhibitors.
The
α
-glucosidase inhibitors
(acarbose, miglitol) block the action of intestinal brush
border enzymes that break down complex carbohy-
drates.
32
By delaying the breakdown of complex carbohy-
drates, the
α
-glucosidase inhibitors delay the absorption
of carbohydrates from the gut and blunt the postprandial
increase in plasma glucose and insulin levels. Although
not a problem with monotherapy or combination therapy
with a biguanide, hypoglycemia may occur with concur-
rent sulfonylurea treatment. If hypoglycemia does occur,
it should be treated with glucose (dextrose) and not
Impaired insulin secretion
Excessive glucagon secretion
Carbohydrate absorption
Intestines
Pancreas
Liver
Fat cells
Skeletal muscle
Decreased insulin-stimulated
glucose uptake
Increased basal hepatic
glucose production
Type 2
Diabetes
A
B
Insulin
secretion
Major effect
Minor effect
Glucagon
secretion
Glucose absorption
Peripheral glucose
uptake
Hepatic glucose
output
Biguanides
Biguanides
Thiazolidinediones
Thiazolidinediones
α
-Glucosidase inhibitors
Amylin analogs
Insulin
secretagogues
Incretins
Amylin analogs
Incretins
Type 2
Diabetes
FIGURE 33-8.
(A)
Mechanisms
of elevated blood glucose in type
2 diabetes mellitus.
(B)
Action
sites of hypoglycemic agents
and mechanisms of lowering
blood glucose in type 2 diabetes.
The incretins are the dipeptidyl
peptidase-4 (DPP-4) inhibitors
and glucagon-like peptide-1
(GLP-1) agonists.
