Pharmacotherapy
• Oral Hypoglycemic
Agents (OHA)
• Antihyperglycemic agents
• Used only in type 2
diabetes, with diet and
exercise
• CDA Clinical Practice Guidelines
“Pharmacologic Management of
Type 2 Diabetes, p S53
Pharmacotherapy
Class: Biguanides (Insulin Sensitizer)
Generic
Brand
Advantages
Disadvantages
Metformin
Glucophage,
Glumetza
-Weight neutral -GI side effects
-low risk of
(nausea, bloating,
hypoglycemia
diarrhea, decreased
appetite)
A1C ↓
1-2%
Mechanism of Action:
↓ hepatic glucose production and intestinal glucose absorption, ↑glucose uptake and
insulin sensitivity, lowers basal and post-prandial blood glucose levels
Comments:
-first line agent in type 2
-good as initial therapy especially if overweight
-best to gradually increase dose to ↓ GI side effects
-Contraindicated if CrCl/eGFR <30 mL/min or hepatic failure
-Caution with renal insufficiency (eGFR<30ml/min)
-lactic acidosis may be precipitated by renal impairment,
excessive alcohol intake, hepatic disease, acute CHF
Pharmacotherapy
Class: Sulfonylureas and Meglitinides
(Insulin Secretagogues)
Generic
Brand
Advantages
Disadvantages
A1C ↓
Glyburide*
Diabeta
-rapid effect
1-2%
Gliclazide
Diamicron
-weight gain, risk of
hypoglycemia,
dizziness, headache,
nausea, weakness
Glimepiride
Amaryl
Repaglinide
Gluconorm
-expensive
Mechanism of Action:
Stimulates functional β cells in pancreas to release insulin, ↓ glucose output from liver
Comments:
-take with food
-hypoglycemia and weight gain are especially common with glyburide*
-caution with patients at high risk of hypoglycemia (e.g. the elderly, renal/hepatic
failure)
Pharmacotherapy
Class: Alpha-glucosidase inhibitors
Generic
Brand
Advantages
Acarbose
Glucobay
-Weight neutral -GI side effects
-low risk of
(diarrhea, gas,
hypoglycemia
cramps, liver
dysfunction)
Prandase
Disadvantages
A1C ↓
0.5-0.75 %
Mechanism of Action:
Delays digestion of CHO and gastrointestinal absorbtion of glucose. Inhibits pancreatic
amylase and membrane bound intestinal α-glucoside hydrolase.
Comments:
-Take with food (first bite of meal)
-Takes up to 8 weeks for maximum efffect
-Not recommended as initial therapy in people with marked
hyperglycemia (A1C >9.0%)
Pharmacotherapy
Class: Tiazolidinidediones (TZD)
or
Glitazones
(Insulin
sensitizers)
Generic
Brand
Advantages
Disadvantages
A1C ↓
Pioglitazone
Actos
Rosiglitazone
Avandia
-improved lipid
profile, low risk of
hypoglycemia,
potential decrease
in MI (pio)
-Slow onset, fluid
retention, weight
gain, bone fractures,
expensive, potential
increase in MI (rosi)
0.5-2%
Mechanism of Action:
↓ insulin resistance, improves target cell response to insulin, ↓ hepatic glucose
production
Comments:
-may induce ovulation
-only covered by blue cross through special authorization –must be intolerant to
metformin
-take at same time everyday
-some blood pressure lowering
Pharmacotherapy
Class: Glucacon Like Peptide 1 (GLP-1)
(Incretins)
Generic
Brand
Advantages
Disadvantages
A1C ↓
Liraglutide
Victoza
Exenatide
Byetta
-weight loss,
low risk of
hypoglycemia
-injection, expensive, 0.5-1.5%
long-term safety not
established, GI side
effects
Mechanism of Action:
Glucagon Like Peptide 1 (GLP-1) receptor agonists act to ↑ insulin release in the
presence of ↑ glucose, ↓ glucagon secretion and delay gastric emptying
Comments:
-may be beneficial for weight loss
-may delay gastric emptying and impact absorption of oral meds (caution with
antibiotics and contraceptives)
-caution with patients at high risk of hypoglycemia
(e.g. the elderly, renal/hepatic failure)
Pharmacotherapy
Class: Dipeptidylpeptidase 4 (DPP-4) Inhibitors
(Incretin)
Generic
Brand
Advantages
Disadvantages
Sitagliptin
Januvia
Saxagliptin
Onglyza
-weight neutral, -expensive, longlow risk of
term safety not
hypoglycemia
established
A1C ↓
0.5-0.75%
Mechanism of Action:
DPP-4 is an enzyme that breaks down the incretin hormones GIP and GLP-1 to help
increase the release of insulin and decrease glucagon levels in the circulation
Comments:
-Better post prandial glucose control
Pharmacotherapy
Insulin
• Rapid Acting
– Humalog (lispro)
• Short Acting
– Humulin R
– Novolin
• Intermediate Acting
– Humulin N
• Long Acting
– Lantus
– Levemir