26
Standards of Medical Care
Table 14. Noninsulin Therapies for Hyperglycemia in
Type 2 Diabetes
Properties of selected glucose-lowering drugs that may guide
individualization of therapy
Class Compound(s) Mechanism Action(s) Advantages Disadvantages Cost
Biguanides • Metformin Activate
AMP-kinase
• Hepatic glucose
production ↓
• Intestinal glucose
absorption ↓
• Insulin action ↑
• No weight gain
• No hypoglycemia
• Reduction in CV
events and mortality
(UKPDS follow-up)
• Gastrointestinal (GI) side effects
(diarrhea, abdominal cramping )
• Lactic acidosis (rare)
• Vitamin B
12
deficiency
• Contraindications: reduced kidney function
Low
Sulfonylureas (SU)
(2nd generation)
• Glibenclamide/
Glyburide
• Glipizide
• Gliclazide
• Glimepiride
Close K
ATP
channels on
β-cell plasma
membranes
• Insulin secretion ↑
• Generally well
tolerated
• Reduction in CV
events and mortality
(UKPDS follow-up)
• Relatively glucose-independent stimulation
of insulin secretion: Hypoglycemia,
including episodes necessitating hospital
admission and causing death
• Weight gain
• May blunt myocardial ischemic
preconditioning
• Low "durability"
Low
Meglitinides • Repaglinide
• Nateglinide
Close K
ATP
channels on
β-cell plasma
membranes
• Insulin secretion ↑
• Accentuated effects
around meal ingestion
• Hypoglycemia, weight gain
• May blunt myocardial ischemic
preconditioning
• Frequent dosing schedule
Medium
iazolidinediones
(glitazones)
• Pioglitazone Activate the
nuclear tran-
scription factor
PPAR-γ
• Peripheral insulin
sensitivity ↑
• No hypoglycemia
• HDL-C ↑
• Triglycerides ↓
• Weight gain
• Edema
• Heart failure
• Bone fractures
High
• Rosiglitazone As above • As above • No hypoglycemia
• LDL-C ↑
• Weight gain
• Edema
• Heart failure
• Bone fractures
• Increased CV events (mixed evidence)
• FDA warnings on CV safety
• Contraindicated in patients with heart
disease
High
α-Glucosidase
inhibitors
• Acarbose
• Miglitol
Inhibit
intestinal
α-glucosidase
• Intestinal carbohydrate
digestion (and,
consecutively,
absorption) slowed
• Nonsystemic
medication
• PPG ↓
• GI side effects (gas, flatulence, diarrhea)
• Frequent dosing schedule
Medium
