-
metformin MOA
- decrease hepatic glucose production
- decrease intestinal glucose absorption
- increase insulin actoin
-
advantages of metformin
- decrease A1c 1-1.5
- weight loss or neutral
- decrease cardiovascular events
- increase insulin sensitivity in obese pts
- low cost
-
adverse effects of metformin
- GI disturbances
- metallic taste
- B 12 deficiency
- rash
- lactic acidosis (rare)
-
what is the root of lactic acidosis for metformin
decreased glucose production -> increase pyruvate -> increased lactic acid
-
CI/cautions for metformin
- renal insufficiency
- scr > 1.5 male, >1.4 female
- severe hepatic insufficiency
- severe/acute CHF
- acute MI
- radiographic dyes
-
drug interactions for metformin
- alcohol increases risk for lactic acidosis
- cephalexin, cimetidine increase metformin levels
- contrast dye increase toxic effects
-
typical patient candidate for metformin
- TIIDM with
- obesity and/or
- insulin resistance
- "pre-diabetes"
- PCOS
-
Glucophage dosing
- begin with 500 mg QD/BID
- titrate to a max of 2550 mg/day
- take with food
-
glucovance dosing
- starting does 1.25mg/250mg QD/BID
- max dose 20mg/2000mg
-
what is glucovance and its strengths
- glyburide and metformin
- 1.25/250 mg
- 2.5/500 mg
- 5/500 mg
-
-
sulfonylureas MOA
stimulate endogenous insulin release from pancreas
-
advantages of sulfonylureas
- decrease A1c 1-1.5
- well tolerated
- decrease CV events
- low cost
-
disadvantages of sulfonylureas
- hypoglycemia
- vigorous exercise
- skip meals
- weight gain
-
avoid/caution for sulfonylureas
- renal impairment
- hepatic impairment
- G6PD deficiency = anemia's
- elderly
- malnutritioned
-
major adverse effect with sulfonylureas
- anemias
- hepatitis
- jaundice
- hyponatremia
-
sulfonylureas drugs
- glipizide - glucotrol
- glimepride - amaryl
- glyburide - diabeta, micronase, glynase (micronized)
-
glipizide dosing
- max 40 mg QD, XL 20mg/day
- doses > 15 mg/day - divide them
- give 30 minutes before meal
- adjustments
- renal - CrCl < 50, decrease by 50%
- hepatic - start at 2.5 mg QD
-
glyburide dosing
- micronized (glyset)
- hepatic - avoid in severe
- renal - CrCl < 50 not recommended
1.25 - 20 mg QD/BID
-
glipizide strengths
- regular - 5,10
- XL - 2.5,5,10,20
-
glyburide strengths
- regular - 1.5,2.5,5
- micronized - 1.5,3,6
-
glimepride dosing
- max 8mg/day
- give w/first main meal
- renal impairment - start 1 mg QD titrate & monitor
- hepatic - same as renal
-
meglinitides
- repaglinide - prandin
- nateglinide - starlix
-
meglinitide MOA
- increase insulin secretion (rapid) - glucose dependent
- like a short acting sulfonylurea
-
meglinitides advantages
- decrease A1c .5-1
- better postprandial glucose lowering - increased physiologic insulin release after a meal
- but can lower fasting as well
-
meglinitide disadvantages
- hypoglycemia
- weight gain
- dosing frequency - TID/QID
-
meglinitides CI's
- hypersensitivity
- children
- pregnancy
-
repaglinide (prandin) dosing
- 4mg/meal or 16 mg/day
- if meal is skipped, skip dose
- renal - CrCl 20-40, start at 0.5 mg titrate carefully
- CrCl < 20 don't do
- hepatic not defined
-
nateglinide dosing
- 120 mg TID
- renal - no adjustments
- hepatic - mod-severe impairment, caution advised
-
meglinitides adverse effects
- HA
- upper respiratory tract infections
- hypoglycemia, but less than OSA
- cardiovascular, but less than metformin
-
meglinitide considerations
- role in therapy - post-prandial hyperglycemia
- poor response if same for OSAs
- don't combine with OSAs
- give 0-30 minutes before meal
- cost medium
-
thieazolidinediones (glitazones)
- actos - pioglitazone
- Avandia - rosiglitazone
-
TZD MOA
- PPAR-y
- increases peripheral insulin sensitivity
- decreased hepatic glucose production
-
adverse effects of TZD's
- edema
- wt gain
- bone fractures
- bladder cancer
- HF risks
-
TZD renal & hepatic considerations
- renal - none
- hepatic don't start if ALT is > 2.5 ULN
-
TZD advantages
- decrease A1c .5-1.5
- possible - increases HDL
- decrease triglycerides
-
roles in therapy of TZD's
- help with insulin resistance
- PCOS - induce ovulation
-
actos - pioglitazone dosing
- 15-45 mg/day as a single dose
- may be taken with or without food
-
alpha-glucosidase inhibitors MOA
inhibition of alpha glucosidase slows intestinal carbohydrate digestion and absorption
-
alpha glucosidase inhibitors advantages
- decrease A1c .5-1%
- non-systemic
- reduces post prandial glucose
-
alpha glucosidase inhibitors adverse effects
- GI - flatulence, possible liver enzyme elevations, abdominal pain, diarrhea
- multiple dosing
- medium cost
-
alpha glucosidase inhibitors
- acarbose - precose
- miglitol - glyset
-
alpha glucosidase inhibitors dosing
- 25 mg TID, may start lower
- maintenance 50 mg TID with meals
-
GLP-1 agonists
- exenatide - byetta (injectable)
- exenatide - bydureon (extended release)
- liraglutide - victoza (injectable)
-
DPP-4 inhibitors
- sitagliptin - januvia
- linagliptin - tradjenta
- saxagliptin - onglyza
-
GLP-1 agonist MOA
- increases insulin secretion
- decrease glucagon secretion
- slows gastric emptying
- increases satiety
-
GLP-1 advantages
- weight reduction
- decrease A1c 1-1.5%
- potential for B cell mass/function
-
GLP-1 disadvantages
- GI - acute pancreatitis, N/V, diarrhea, HA
- hypoglycemia - reduce OSA dose
- thyroid cell cancer (rodents) - victoza
- long term safety unknown
- high cost
-
-
byetta - exenatide dosing
- 5 mcg BID
- titrate to 10 mcg BID
-
victoza - liraglutide dosing
- 0.6 mg SC QD
- max 1.8 mcg/day
- independent of meals
-
DPP-4 inhibitors MOA
- increase GLP-1 concentration
- increase insulin secretion
- decreases glucagon secretion
-
DPP-4 I advantages
- decrease A1c .5-1
- improves both fasting and postprandial levels
- weight neutral
-
DPP-4 I adverse effects
- pancreatitis
- itching, urticatia
- increased URI incidences
- dizziness
- diarrhea
- diaphoresis
-
sitagliptin - Januvia dosing
- 50 - 100 mg daily
- 50 mg if CrCl <30-50ml/min
- 25 mg if CrCl < 30ml/min
-
saxagliptin - onglyza dosing
- 2.5 - 5 mg daily
- 2.5 mg daily if CrCl < 50ml/min
-
lingaliptin - tradjenta dosing
- 5 mg QD
- no renal or hepatic dosing
-
bile acid sequestrant
colesevelam
-
dopamine - 2 agonist
bromocriptine
-
bile acid sequestrants adverse effects
- increases TG
- interferes with medication absorption
- constipation
-
DA 2 agonist adverse effects
-
DA 2 agonist MOA
increases insulin sensitivity
-
5 factors contributing to metabolic syndrome
- central obesity
- high blood pressure
- high triglycerides
- low HDL
- insulin resistance
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