Diabetes Drugs

Question 1

Biguanide - Metformin

1) Clinical Indication?
2) Mechanism of Action?
3) Hypoglycemia? Weight gain?
4) Clinical Benefits? Mortality Benefits?

Answer 1

1) Should be the #1 choice unless there are contraindications
2) Decreases glucose production in the liver
- -Insulin sensitizer and lowers insulin and lipid levels
3) No hypoglycemia or weight gain
4) Improves cardiovascular outcomes in overweight and newly diagnosed type 2 diabetics
- - decreases mortality!!!

Question 2

Biguanide - Metformin

1) Any clinical indications for special populations?
2) Category in Pregnancy?
3) Used in any other disease?

Answer 2

1) Only oral medication for use in children and adolescents
2) Category B in pregnancy
3) Used for polycystic ovary disease

Question 3

Biguanide - Metformin

1) Use with caution in which population? and which diseases?
2) You must stop Metformin before which kinds of procedures? and how long?
3) What GFR can you continue metformin? Do not initiate metformin below what GFR?
4) What vitamin deficiency do you check for?

Answer 3

1) Use with caution in the elderly (> 65), renal dysfunction, cardiopulmonary disorders (OK with stable CHF), and hepatic disease
– BUT: decreased mortality in heart failure, kidney and liver disease
2) Stop prior to IV contrast and 48 hours after** (angiography/pyelography)
- Must check creatinine prior to use*
3) New data suggests that it can be renal dosed if
GFR > 30 mL/min)
– Do not initiate if GFR < 45 mL/min
4) Check for B12 deficiency** (no defined interval)

Question 4

Thiazolidinediones
Pioglitazone (Actos)
1) Mechanism of Action?
2) Caution with which kind of disorders? and why?
3) Which labs do you order for monitoring?

Answer 4

1) Insulin sensitizers** (decrease insulin resistance)*
– ↓ gluconeogenesis (increase hypoglycemia)
2) Caution in cardiopulmonary disorders (fluid retention–volume overload)*
– Black Box warning for class III or IV heart failure
3) Monitor LFTs, avoid in hepatic dysfunction, but can be useful in nonalcoholic
steatohepatitis

Question 5

Thiazolidinediones
Pioglitazone (Actos)
1) Do not use in..?
2) Increase risk of which cancers?

Answer 5

1) Decrease bone density and increase fractures (don’t use in osteoporosis)
2) Increased risk of pancreatic, bladder, prostate cancers

Question 6

Sulfonylureas:
– Glipizide (Glucotrol)
– Glyburide
– Glimepiride (Amaryl)

1) Mechanism of action?
2) Hypoglycemia? Weight gain/loss/neutral?
3) Which one the three do you avoid in elderly?

Answer 6

1) Stimulate pancreatic beta cells to release insulin
2) Weight gain and hypoglycemia
3) Can be used in low doses in the elderly (avoid glyburide)

Question 7

Sulfonylureas:
– Glipizide (Glucotrol)
– Glyburide
– Glimepiride (Amaryl)

1) Any renal precautions?
2) Any cardiopulmonary precautions?
3) Gestational Diabetes?
4) May increase… in women?

Answer 7

1) OK in mild renal dysfunction (except glyburide has an active
metabolite eliminated by the kidneys)*
2) OK in cardiopulmonary comorbidities (sleep apnea, CHF)
3) Glyburide in and out of favor in gestational diabetes
4) May increase fractures (especially hip) in women

Question 8

Meglitinides:
– Repaglinide (Prandin)
– Nateglinide (Starlix)

1) Mechanism of action?
2) Can it be used in elderly? renal failure? cardiopulmonary disorders?
3) Why would you use this drug?

Answer 8

1) Rapid-acting (half-life <1 hr) insulin secretagogues
2) May be used in elderly, renal failure, and cardiopulmonary
disorders
3) Helpful for erratic eating schedules (i.e. old ladies who get hypoglycemic who don’t eat regularly. take this pill with meal)

Question 9

Alpha-Glucosidase Inhibitors:
– Acarbose (Precose)
– Miglitol (Glyset)

1) Mechanism of action?
2) Any CVS benefits?
3) Monitor which labs?
4) Can it be used in renal failure? cardiopulmonary disorders?
5) Weight loss/gain/neutral?

Answer 9

1) Delay carbohydrate absorption in gut—decrease peak glucose levels, no
hypoglycemia as monotherapy
2) Reduces risk of cardiovascular events* (STOP NIDDM)
3) Monitor LFTs; avoid in cirrhosis, GI disease
4) Not for use in renal dysfunction (creatinine > 2)*
5) Weight neutral

Question 10

GLP-1 Receptor Agonists:
– Exenatide (Byetta)
– Liraglutide (Victoza)
– Albiglutide (Tanzeum)
– Dulaglutide (Trulicity)
– Lixisenatide (Adlyxin)

1) Mechanism of Action?
2) Side Effects?
3) Increased which cancer risk?
4) Can it be used in renal failure? If so, which one of the above can be used?

Answer 10

1) Potentiate insulin secretion
– Suppress postprandial glucagon secretion
– Slow gastric emptying
– Promote satiety (no weight gain)
2) Nausea, vomiting, diarrhea, weight loss**
– Pancreatitis*
– Hypoglycemia (with sulfonylurea)
3) Thyroid C-cell tumor risk
4) Decrease dose in renal failure (except liraglutide). Avoid if creatinine clearance < 30 mL/min

Question 11

DPP-4 Inhibitors:
– Sitagliptin (Januvia) 
– Saxagliptin (Onglyza) 
– Alogliptin (Nesina) 
– Linagliptin (Tradjenta) 

1) Mechanism of action?
2) Which diabetes drug can it not be combined with??
3) Weight loss/gain/neutral?

Answer 11

1) Block dipeptidyl peptidase 4 (enzyme that breaks down natural incretins)
• Better insulin release and blood sugar control, particularly postprandial
2) Don’t add to sulfonylurea in the elderly*
• Linagliptin not renally excreted and good choice in elderly
3) Weight neutral

Question 12

SGLT2 Inhibitors:
– Canagliflozin (Invokana), Can use to GFR<45
– Dapagliflozin (Farxiga), Can use to GFR <60, Has been used in type 1
diabetes
– Empagliflozin (Jardiance), Can use to GFR<45, For advanced renal disease

1) Mechanism of action?
2) Any CVS benefits?
3) Weight loss/gain/neutral?
4) Adverse effects?

Answer 12

1) Block reabsorption of glucose in the kidney
– Increase urinary excretion of glucose
2) Decrease risk of MI, stroke, cardiovascular
death
3) Decrease weight
4) B12 deficiency
– May predispose to DKA
– Increase fractures and risk of foot
amputation
– Increased UTIs and genital infections