29
Table 14. Noninsulin Therapies for Hyperglycemia in
Type 2 Diabetes (continued)
Properties of selected glucose-lowering drugs that may guide
individualization of therapy
Class Compound(s) Mechanism Action(s) Advantages Disadvantages Cost
GLP-1 receptor
agonists
(incretin mimetics)
• Exenatide
• Liraglutide
Activate GLP-1
receptors (β-cells/
endocrine pancreas;
brain/autonomous
nervous system)
• Insulin secretion ↑
(glucose-
dependent)
• Glucagon
secretion ↓
(glucose-
dependent)
• Slows gastric
emptying
• Satiety ↑
• Weight reduction
• Potential for improved
β-cell mass/function
• GI side effects (nausea, vomiting, diarrhea)
• Cases of acute pancreatitis observed
• C-cell hyperplasia/medullary thyroid tumors
in animals (liraglutide)
• Injectable
• Long-term safety unknown
High
DPP-4 inhibitors
(incretin
enhancers)
• Sitagliptin
• Saxagliptin
• Linagliptin
Inhibit DPP-4 activ-
ity, prolongs survival
of endogenously
released incretin
hormones
• Active GLP-1
concentration ↑
• Active GIP
concentration ↑
• Insulin secretion ↑
• Glucagon
secretion ↓
• No hypoglycemia
• Weight "neutrality"
• Occasional reports of urticaria/angioedema
• Cases of pancreatitis observed
• Long term safety unknown
High
Sodium-glucose
co-transporter 2s
(SGLT2)
• Canagliflozin
• Dapagliflozin
Inhibit
sodium-glucose
co-transporter 2
• Reabsorption of
filtered glucose ↓
• Urinary glucose
excretion ↑
• No hypoglycemia
• ↓ HbA1C
• ↓ FPG and PPG
• Weight reduction
• ↓BP
• Female genital mycotic infections
• Nasopharyngitis
• Urinary tract infection
• Increased urination
High
Bile acid
sequestrants
• Colesevelam Binds bile acids/
cholesterol
• Unknown • No hypoglycemia
• LDL-C ↓
• Constipation
• Triglycerides ↑
• May interfere with absorption of other
medications
High
Dopamine-2
agonists
• Bromocriptine Activates dopami-
nergic receptors
• Alters
hypothalamic
regulation of
metabolism
• Insulin sensitivity ↑
• No hypoglycemia • Dizziness/syncope
• Nausea
• Fatigue
• Rhinitis
• Long-term safety unknown
Medium
Adapted with permission from Silvio Inzucchi, Yale University.
