Antidiabetic Agents

Question 1

Sulfonylureas

Answer 1

Examples: glimeperide (amaryl), glipizide (glucotrol), glyburide

MOA: Binds to sulfonylurea receptor on beta cells, stimulating insulin release

Efficacy: -1 to 2%

Benefits: Extensive experience, improved microvascular outcomes in studies; low cost; daily dosing

Risks: hypoglycemia, weight gain, may impede ischemic preconditioning

Question 2

Meglitinides (Non-sulfonylurea insulin secretagogues)

Answer 2

Examples: repaglinide (prandin), nateglinide (starlix)

MOA: Binds to sulfonylurea receptor on beta cells, stimulating insulin release

Efficacy: -1 to 1.5%

Benefits: Targets post-prandial glucose; mimics physiological insulin secretion

Risks: hypoglycemia; weight gain; no long-term experience; expensive; frequent dosing

Question 3

Biguanides

Answer 3

Examples: metformin (glucophage)

MOA: decreases hepatic glucose production

Efficacy: -1 to 2%

Benefits: weight loss or weight neutrality; no hypoglycemia; extensive experience; improved macrovascular outcomes in studies; daily dosing available

Risks: diarrhea; lactic acidosis; many contraindications to consider prior to prescribing; lowers vitamin B-12 levels (but no apparent effects on hematological indices)

*preferred initial agent in Type 2 DM

Question 4

alpha glucosidase inhibitors

Answer 4

Examples: acarbose (precose), miglitol (glyset)

MOA: retards gut carbohydrate absorption

Efficacy: -0.5%

Benefits: targets post-prandial glucose; weight neutral; no hypoglycemia; non-systemic

Risks: intestinal gas; expensive; frequent dosing

Question 5

thiazolidinediones

Answer 5

Examples: rosiglitazone (avandia), pioglitazone (actos)

MOA: activates PPAR-y, increasing peripheral insulin sensitivity

Efficacy: -1 to 1.5%

Benefits: addresses primary defect of Type 2 DM; no hypoglycemia; lipid and other “non-glycemic” vascular benefits; potential anti-atherosclerotic properties (pioglitazone); potential for beta cell preservation; daily dosing

Risks: edema; HF in predisposed individuals; weight gain; inc in bone fx in women; slow onset of action; expensive; liver monitoring still advised; rosiglitazone may increase risk of MI

*contraindicated in NYHA Class III and IV patients

Question 6

DPP-4 Inhibitors

Answer 6

Examples: sitagliptin (januvia), saxagliptin (onglyza)

Efficacy: 0.6 to 0.8%

MOA: inhibits enzyme that deactivates endogenous incretins, GLP-1 and GIP, thereby increasing glucose-dependent insulin release and suppressing glucagon secretion

Benefits: low incidence of SE; no hypoglycemia; daily dosing; potential beta cell preservation

Risks: expensive; limited clinical experience; urticaria and angioedema reported; pancreatitis recorded

Question 7

Bile acid sequestrants

Answer 7

Examples: colesevelam (welchol)

Efficacy: -0.4 to 0.5%

MOA: unknown

Benefits: LDL reduction; non-systemic

Risks: constipation; increases triglycerides; multiple pills per day; expensive

Question 8

dopamine-2 agonists

Answer 8

Examples: bromocriptine (cycloset)

MOA: alters hypothalamic neurotransmitter tone and may reduce hepatic glucose production

Efficacy: -0.4 to 0.7%

Benefits: no hypoglycemia; daily dosing

Risks: orthostatic hypotension; dizziness; syncope; exacerbation of psychotic illness; nausea; vomiting; fatigue

Question 9

GLP-1 Mimetics

Answer 9

Examples: exenatide (Byetta), lyraglutide (Victoza)

Efficacy: -1%

MOA: glucose-dependent stimulation of insulin release; suppresses glucagon; retards gastric emptying; enhances satiety

Benefits: weight loss; no hypoglycemia; potential beta cell preservation

Risks: injectable; nausea; expensive; pancreatitis reported

Question 10

amylinomimetics

Answer 10

Examples: pramlintide (symlin)

Efficacy: -0.4 to 0.6%

MOA: suppresses glucagon release; retards gastric emptying; enhances satiety

Benefits: targets post prandial glucose; weight loss

Risks: injectable; nausea; expensive

Question 11

insulin

Answer 11

Efficacy: “no ceiling”

MOA: increases insulin supply

Benefits: extensive experience; rapidly effective in all circumstances; no contraindications; improved microvascular outcomes in studies; mortality benefits in acute settings; low cost

Risks: hypoglycemia; weight gain; injections and more frequent glucose monitoring required; increases complexity of management; “stigma”

Question 12

Rapid acting insulin

Answer 12

lispro (humalog), aspart (novolog), glulisine (apidra)

onset: 10-15min
peak: 1-2hrs
duration: 3-5hrs

Question 13

short acting insulin

Answer 13

regular insulin

onset: 30min-1hr
peak: 2-4hr
duration: 4-8hr

Question 14

intermediate acting insulin

Answer 14

NPH

onset: 1-3hr
peak: 4-10hr
duration: 10-18hr

Question 15

long acting insulin

Answer 15

glargine (lantus) and detemir (levemir)

onset: Lantus: 2-3hr
	   Levemir: 1hr
peak: none
duration: Lantus: 24+hrs
		Levemir: up to 24hrs