John Atlee “Jay” Snyder, D.O. Assistant Professor of Internal Medicine East Tennessee State...
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Outpatient Management of Diabetes Mellitus Type 2: Oral Medications John Atlee “Jay” Snyder, D.O. Assistant Professor of Internal Medicine East Tennessee State University January 24 th 2012
John Atlee “Jay” Snyder, D.O. Assistant Professor of Internal Medicine East Tennessee State University January 24 th 2012
John Atlee Jay Snyder, D.O. Assistant Professor of Internal
Medicine East Tennessee State University January 24 th 2012
Slide 2
Todays Goals 1. To recognize the importance of knowledge of
treatment of diabetics by reviewing the increasing prevalence of
type 2 Diabetes 2. To review the numerous classes of medicines
currently used for oral management of Diabetes 3. To recognize
strategies used for treatment of Diabetes 4. To discuss Diabetes
& driving
Slide 3
www.cdc.gov/diabetes Age-adjusted percent County-level
Estimates of Diagnosed Diabetes among Adults aged 20 years: United
States 2004
Slide 4
www.cdc.gov/diabetes Age-adjusted percent County-level
Estimates of Diagnosed Diabetes among Adults aged 20 years: United
States 2005
Slide 5
www.cdc.gov/diabetes Age-adjusted percent County-level
Estimates of Diagnosed Diabetes among Adults aged 20 years: United
States 2006
Slide 6
www.cdc.gov/diabetes County-level Estimates of Diagnosed
Diabetes among Adults aged 20 years: United States 2007
Age-adjusted percent
Slide 7
www.cdc.gov/diabetes County-level Estimates of Diagnosed
Diabetes among Adults aged 20 years: United States 2008
Age-adjusted percent
Slide 8
2004 Age-Adjusted Estimates of the Percentage of Adults with
Diagnosed Diabetes in Tennessee Centers for Disease Control and
Prevention: National Diabetes Surveillance System. Available online
at: http://apps.nccd.cdc.gov/DDTSTRS/default.aspx. Retrieved
1/20/2012http://apps.nccd.cdc.gov/DDTSTRS/default.aspx. Retrieved
1/20/2012
Slide 9
2005 Age-Adjusted Estimates of the Percentage of Adults with
Diagnosed Diabetes in Tennessee
Slide 10
2006 Age-Adjusted Estimates of the Percentage of Adults with
Diagnosed Diabetes in Tennessee
Slide 11
2007 Age-Adjusted Estimates of the Percentage of Adults with
Diagnosed Diabetes in Tennessee
Slide 12
2008 Age-Adjusted Estimates of the Percentage of Adults with
Diagnosed Diabetes in Tennessee
Slide 13
Who will help us stop this destructive pattern? The food
industry???
Diabetes vs. Obesity 2008 Centers for Disease Control and
Prevention: National Diabetes Surveillance System. Available online
at: http://apps.nccd.cdc.gov/DDTSTRS/default.aspx. Retrieved
1/20/2012http://apps.nccd.cdc.gov/DDTSTRS/default.aspx. Retrieved
1/20/2012
Slide 19
Treating Diabetes
Slide 20
First Line Classes Sulfonylureas Biguanides
Slide 21
Sulfonylureas (Second Generation) Glipizide (Glucatrol,
Glucatrol XL) Glimepiride (Amaryl) Glyburide (Diabeta, Micronase)
-ionized Glyburide (Glynase) also available -ionized doses to
regular Glyburide
Slide 22
Yes Virginia, there is a First generation Sulfonylurea Rarely
used Chlorpropamide (Diabinese) Tolazamide Tolbutamide
Slide 23
Preference for a specific Sulfonylurea? Second generation?
Glipizide because of short half-life? Glimeperide because of a
study showing less hypoglycemia in the elderly? 1 PMID:
19952550/PMID: 8675920
Are there different generations of Biguanides? Originally
introduced in the 1950s, the first biguanides (Phenformin) had a
very high frequency of lactic acidosis & were removed from the
market. Some critics will argue there is not enough evidence of
lactic acidosis 1 Metformin has a much lower incidence of lactic
acidosis but still enough to warrant a Black Box warning. (9 cases
per 100000 person years) 2 1. PMID 20393934. 2. PMID:10372243
Slide 26
Are there other first line meds? Sitagliptin (Januvia) is a
DPP4 previously used as an adjunct that has now been approved as a
monotherapy. Insulin. Very poor control/renal failure/etc but thats
a whole nother presentation.
Slide 27
So which medicine have we started in the past?? Sulfonylurea or
Metformin?
Slide 28
Cardiac concerns? Old study (1970) with first generation
sulfonylurea Tolbutamide showed increased cardiovascular mortality.
1 Some belief that this still persists with all sulfonylureas
including second generation. 2 1. PMID: 992232. 2. PMID
:22250169
Slide 29
Are they Overweight/Obese? Sulfonylureas increase insulin
release from the pancreas & thus can cause weight gain
Slide 30
Are they Overweight/Obese? Metformin helps with weight loss by:
-reduction of GI absorption of glucose. -stimulation of anerobic
glycolysis. (lactic acid) -inhibition of gluconeogenesis.
-stimulation of glucose uptake in the liver. -increasing insulin
receptors.
Slide 31
Dosing=Start low & go slow. Start Sulfonylureas at lower
doses & increase slowly due to concern of hypoglycemia. Start
Metformin at lower doses & increase slowly due to concern of GI
side effects. May even start with PM or HS dosing, then increasing
to BID. (To sleep through the bloating sensation) Also consider the
extended release formula. Max dose Sulfonylurea varies medicine to
medicine Max daily dose Metformin 2550mg/day
Slide 32
Renal failure? Metformin contraindicated due to concerns of
lactic acidosis. Metformin should be held in anticipation of
procedures when IVP dye is used. Sulfonylureas are excreted by the
kidneys & may build up in the bloodstream, thus causing
hypoglycemia.
Alpha-glucosidase inhibitors Acarbose (Precose) Miglitol
(Glyset) Prolong digestion of carbohydrates & reduce peak
glucose levels by blocking oligosaccharide binding to the brush
border. Taken with first bite of the meal & has additive
effects when combined with sulfonylurea. Side effects: -GI related.
Worse with Acarbose (including elevated LFTs & ileus)
Slide 41
Oral Beta cell stimulators Repaglinide (Prandin) technically a
Meglitinide Nateglinide (Starlix) technically amino acid derivative
Action similar to sulonylureas, working in a glucose dependent
fashion but still with the risk of hypoglycemia. Have a very short
half-life & must be taken with meals. Some consideration as
first line therapy in renal failure Side effects: - URI symptoms
& GI side effects. Rare cardiac ischemia with Prandin &
rare accidental injury with Starlix
Slide 42
Thiazolidinediones (TZDs/Glitazones) Pioglitazone (Actos)
Rosiglitazone (Avandia) Very good for additional control. Agonists
of PPARgamma. Work at the tissue level to increase insulin
sensitivity. Side effects: -may cause or worsen heart failure -rare
hepatotoxicity -fractures (in women only) 1 -Bladder cancer 2 1.
PMID: 17363747. 2. PMID: 21515844.
Slide 43
Slide 44
Incretin Mimetics (GLP-1s) Exanatide (Byetta) Liraglutide
(Victoza) Lixisenatide (Lyxumia) soon to be released Works as a
glucogon-like peptide (GLP-1) to increase glucose dependent insulin
secretion, decrease excessive glucagon secretion, slow gastric
emptying & decrease appetite. $$$ & bid injections. If
willing to do injections why not just do insulin?? Side effects:
-Suppresses appetite -Associated with pancreatitis -Rarely
associated with acute renal failure -Injection site concerns?
Slide 45
Dipeptidyl peptidase-4 inhibitors (DPP4s) Sitagliptin (Januvia)
Saxagliptin (Onglyza) Linagliptin (Tradjenta) recently released By
blocking DPP4, incretins including GLP-1 are increased & effect
is similar to incretin mimetics. Side effects: -URI symptoms
-pancreatitis
Slide 46
Cancers with GLP-1s/DPP4s With known risk for pancreatitis in
Exanatide & Sitagliptin, a review also found an increased risk
for pancreatic cancer with these medicines Also thyroid cancer in
Exanatide PMID: 213343333
Slide 47
Slide 48
Bile acid sequestrants Colesevelam (Welchol) Cholesterol
medicine shown to improve glucose control/lower A1C. Side effects:
-GI (including obstructions starting at the esophagus & ending
with fecal impaction) -Oral blisters/severe rash
Slide 49
Amylin analogues Pramlintide (Symlin) Increased risk of
hypoglycemia (especially with insulin)
Slide 50
The elephant in the room INSULIN
Slide 51
Combination meds Too many to count!!!! If on multiple
medicines, see if there is an option. Only Sulfonylureas & Beta
cell stimulators (& insulin/amylin) can cause hypoglycemia.
However, additional medicines may enhance the hypoglycemia caused
by sulfonylureas.
Slide 52
Future medicine options Weekly/Depot Byetta shots. More me too
drugs such as DPP4 meds Vildagliptin & Alogliptin.
Bromocriptine mesylate (Cycloset) is a dopamine agonist on the
market with unknown mechanism of improved diabetic control. More
meds like this soon? Other PPAR agonists. PPAR alpha, beta, or
combinations with gamma. (TZDs only gamma)
Slide 53
Future medicine options Dapaglifozin Works as a SGLT2
inhibitor. Works at sodium-glucose cotransporter 2 in kidneys to
prevent glucose being reabsorbed & thus to be lost to the
urine. Increased incidence of UTIs Increased incidence of bladder
cancer ?Increased incidence of breast cancer PMID: 22262072
Slide 54
Even more combination meds Juvisync (Januvia & Simvastatin)
approved recently
Slide 55
Which medicine do we start?
Slide 56
Recent systematic review in the Annals of Internal Medicine
..overall guideline quality was poor with respect to the rigor of
the guideline development process, particularly in use of
systematic methods to identify evidence. In addition, most
guidelines were susceptable to bias because they lacked a
description of editorial independence from funders and guideline
developers failed to report potential conflicts of interest. PMID:
22213492
Slide 57
Recent systematic review in the Annals of Internal Medicine 11
guidelines met the inclusion criteria. Seven guidelines agreed with
the conclusion that metformin is favored as the first-line agent
The American Diabetes Association has also recently clarified its
preference for metformin
Slide 58
Which medicine to add on? New England Journal of Medicine
interactive clinical decisions survey January 2008 Patient on
Metformin & Glipizide with fasting morning glucose of 110-140
& HbA1C of 8.1% Adding Pioglitazone, NPH before bedtime or
Exanatide twice daily PMID: 18272888
Staying up to date Dont forget to check the American Diabetes
Associations website in the beginning of every January for updates
on recommendations.
Slide 61
Question A patient with poorly controlled DM2 comes in the
office for a follow-up & yearly physical. The patient notes
that if they were placed on insulin, they would no longer be able
to work in their current profession & they would be fired
Slide 62
What is your patients job? A. Nurse B. Teacher C. Carpenter D.
Truck driver E. Chef
Slide 63
Answer D. Truck driver
Slide 64
Diabetes & driving
Slide 65
But wait a minute!! From the Instructions for the Medical
Examiner section of the Medical Examination Report for Commercial
Driver Fitness Determination: CMV drivers who do not meet the
Federal diabetes standard may call (202) 366-1790 for an
application for a diabetes exemption Diabetes Exemption Team (202)
366-4001
Slide 66
Insulin & Truckers Timeline 1986: ADA & others
petitioned to grant waivers on a case- by-case basis 1993: Waiver
program granted for those with safe driving history &
endocrinologist/ophthalmologist approval. 1996: Appeals court ruled
the program illegal (Advocates for Highway and Auto Safety v
Federal Highway Administration) 2003: Federal waiver process
established with an exemption for for interstate commerce Now: Most
states are adopting similar process to Federal rule for their CDLs
http://www.fmcsa.dot.gov/facts-research/research-technology/tech/TB-02-01-1.htm
Slide 67
ADA Guidelines An entire section for Diabetes & Driving
...people with diabetes should be assessed individually, taking
into account each individual's medical history as well as the
potential related risks associated with driving. Potential
medical-legal ramifications
Slide 68
Todays Goals 1. To recognize the importance of knowledge of
treatment of diabetics by reviewing the increasing prevalence of
type 2 Diabetes 2. To review the numerous classes of medicines
currently used for oral management of Diabetes 3. To recognize
strategies used for treatment of Diabetes 4. To discuss Diabetes
& driving