Diabetes Drugs
Insulin
Type/Name Begins Peaks At Stops Lows Occur
Working Working
Humalog 15-20 min. 30-90 min. 3-4 h 2-4 h
Novolog 15-20 min. 40-50 min. 3-4 h 2-4 h
Regular 30-60 min. 80-120 min. 4-6 h 3-7 h
NPH 2-4 h 6-10 h 14-16 h 6-12 h
Lente 3-4 h 6-12 h 16-18 h 7-14 h
UltraLente 4-6 h 10-16 h 18-20 h 12-24 h
Lantus 2-3 h no peak 18-26 h 4-24 h
Adverse: HYPOGLYCEMIA, liposystrophy, allergic reactions (esp. w/ non-human)
Intxns: beta-blockers contribute to hypos by masking catecholamine response to lows
Notes:
general mech:
o glucose is taken up by beta cells in pancreas (does not require insulin)
and is phosphorylated = increase in cellular ATP.
o Increased ATP causes a block in K+ channels = membrane
depolarization (becomes more negative) – leads to Ca++ influx
o increased intracellular Ca++ causes pulsatile exocytosis of insulin
is always used in Type 1 (pancreatic destruction) and used in more advanced
cases of Type 2 (insulin resistance)
absorption is quickest through the abdomen, followed by the arms and legs
more than one insulin type often used to cover daily living and meals (and fun)
Sulfonylureas
Drug Duration Daily Relative Risk of
of Axn Dose Potency Low BG
1st Orinase 6-10 h 500 – 3000 mg 1 < 1%
Gen (tolbutamide)
Tolinase < 4%
(tolazamide)
Diabinase 24-72 h 2.5 – 40 mg 6 4-6%
(chlorpropamide)
2nd Glucotrol 12-24 h 2.5 – 40 mg 75
Gen (glipizide)
Glucotrol XL 2.5 – 20 mg 150
(extended release)
Micronase, Diabeta 18 – 24 h 1.25 – 20 mg 150 4-6%
(glyburide)
Amaryl 24 h 1-8 mg 300 < 2%
(glimepiride)
Target Organ: Pancreas
Action: Increase Insulin Release
Adverse: low blood sugar (possibly hypos), bloating, heartburn, nausea (1-3%
incidence), anemia, metallic taste or change in taste, crosses placenta
Notes
effects:
o stumulation of insulin release from b-cells of pancreas
o reduction of serum glucagon levels
o increased binding of insulin to target tissues and receptors
useless if no pancreas evidenced by low C-peptide levels (by-products of
insulin detectable in blood)
1st generation are as effective in lowering BG, but have more X-reactivity with
other drugs – they are transported in the blood by albumin, and can be
dislodged by other drugs = unexpected reactivity
Glimepiride does not block dilation of blood vessels, and does not affect
coronary arteries – effects sometimes seen with other sulf’s
Biguanides
Drug Duration of Dose Range Risk of
Axn Low BG
Glucophage 8h 500 – 2500 mg < 1%
(metformin)
Glucovance 250/1.25 mg – < 4%
(metformin and 200/20 mg
glyburide)
Target Organ: liver, secondary effects on muscle and fat
Axn: lowers glucose production by liver, increases insulin receptors
on muscle and fat cells
Side Effects: LACTIC ACIDOSIS, bloating, diarrhea, B12 defic.,
headache, agitation
Contraind: DKA, alcoholism, kidney or liver ds, CHF
Notes:
in huge UKPDS study, was only drug shown to reduce diabetes-related death
rates, heart attacks and strokes
has long history of safe use in Europe, Canada, Mexico, but only approved for
US in 1994
can cause mild weight and BP reductions
lactic adicosis caused by buildup of lactic acid due to inability to clear drug –
usually in older people with at least one other major illness
o warning signs = fast, shallow breathing, diarrhea, severe muscle
aches/cramps
o mortality of 40%
Alpha-glucosidase inhibitors
Drug Duration of Dose Range Risk of
Action Low BG
Precose 4h 12.5 – 100 mg none
(acarbose) before meal
Glyset 12.5 – 100 mg none
(miglitol) before meal
Target Organ: intestine
Action: slows breakdown of carbs
Side Effects: bloating, diarrhea, nausea, excess gas, abdominal pain
Contraind: liver disease, bowel or intestinal ds, intest. obstruction
Notes:
most effective for complex carbs – prevents postprandial glucose spikes,
allows for patient to naturally respond to meals even with reduced insulin
response
can also slightly lower fasting blood sugars
if a concurrent diabetes drug causes hypoglycemia – it must be treated with
milk or glucose tablets (simple carbs) because acarbose will block effects of
some sugars, fruit and fruit juice
Thiazolidinediones
Drug Duration of Dose Range Risk of
Action Low BG
Actos 8h 15 – 45 mg < 2%
(pioglitazone)
Avandia 2 – 8 mg
(rosiglitazone)
Target Organ: muscle, fat, liver
Action: improves receptivity in insulin receptors
Side Effects: URI’s, headaches, muscle aches, tooth aches, sore throat
Contraind: kidney or liver disease, enlarged heart, swelling, pregnancy
Notes:
work by reducing levels of inflammatory particles like TNF-alpha and PPAR
gamma
also prevent liver from overproducing glucose (source of liver toxicity in
others in this class)
strange side-effect – have increased fertility in women with POD causing
unwanted pregnancies
liver testing MANDATORY every 2 months for the first year – if ALT rises
more than 3x upper normal, STOP
o 50 people died on original thia on market called Rezulin (troglitazone)
Meglitinides – 1st Phase Insulin Releasers
Drug Duration of Dose Range Risk of
Action Low BG
Prandin 3h .5 – 4 mg < 1%
(repaglinide) before meal
Starlix 60 – 120 mg < 2.5%
(neteglinide) before meal
Target Organ: pancreas
Action: increases 1st phase insulin release, is glucose-driven, lowers
after-meal glucose levels
Side Effects: hypoglycemia, URI, cold and flu-like sx, joint aches
Contraind: type 1 diabetes, DKA, liver ds
Increased effect: NSAIDS, salicylates, sulfonamides, chloramphenicol
MAOIs, probenecid
Decreased effect: Ca chan blockers, corticosteroids, oral contraceptives
thiazide diuretics, thyroid preparations, estrogens, phenytoin, INH
Notes:
because they respond to the glucose level, there is less chance for hypos than
sulfs (and is milder if it does occur)
taken 15 minutes b/4 a meal – often called “oral insulin” people with diabetes
most effective for people who have large BG spikes after meals, but who have
nominally high fasting glucose levels
ok to use if kidney fxn damage