The document outlines an upcoming presentation on diabetes management. It will review guidelines from major organizations for treating diabetes, discuss treatment goals and hemoglobin A1c levels, and compare the most effective, common, and economical medication options. It will also touch on alternative/complementary therapies and emphasize smoking cessation, blood pressure control, and other lifestyle factors important in diabetes care. Key treatment algorithms and medications to be covered include metformin, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, GLP-1 agonists, and insulin. References from guidelines, reviews, and textbooks will be used.

1. Clinton Pong PGY-3
Family Medicine 8/2012

2.  Review DM management and challenge
the limits of our repertoire
 Discuss A1c’s role in treatment as a goal
 Review MA, PCHI, ADA and ACE/ACCE
algorithms for treatment
 Discuss most effective, most common and
most economical treatments
 Review EBM
 If we get to it, talk about some
Alternative/Complementary Med

3.  This is NOT a talk about “diabetes
priorities”
 What are they? (Talk to the “HAND”)
1. Smoking cessation
2. Blood pressure control
3. Lipid control
4. Metformin (and aspirin)
5. Glycemic control
6. Vaccinations

4. Or: 125+ 30 per % point
above 6%.
~125
~155
~185
~215
~245

6. David M. Nathan, Judith Kuenen, Rikke Borg, Hui Zheng, David
Schoenfeld, and Robert J. Heine, for the A1c-Derived Average
Glucose (ADAG) Study Group. Translating the hemoglobin A1c
assay into estimated average glucose values. Diabetes Care 2008

8.  EE Plus, DynaMed, MA and PCHI
guidelines all agree:
 Most validated method is:
1. Start with Metformin
• crank it up as tolerated
• max dose 850mg PO TID
1. Add on a Sulfonylurea (or skip to 3)
• Glipizide or glimeride
1. Then start Insulin

11. Treatment of Type 2 Diabetes
Incretin & DPP-IV inhibitor
Skeletal
muscle and
Metformin adipose
TZD Liver TZD tissue
Metformin Glucose
Hepatic uptake
glucose
output
Pancreas
Slowed GI Insulin
glucose secretion
absorption Decrease
SU/Meglitinide Hyperglycemia
Alpha-Glucosidase
Inhibitor

12.  A 66-year-old male with type 2 diabetes mellitus
is seen for a follow-up visit and has a
hemoglobin A1c of 6.7%. He is currently taking
metformin (Glucophage), 1000 mg twice daily
He has no history of coronary artery disease or
heart failure.
Which one of the following would be most
appropriate?
A) Continuing his current regimen
B) Increasing the metformin dosage
C) Adding a sulfonylurea
D) Adding a thiazolidinedione
E) Adding daily long-acting insulin

13.  $, Cheap and reduces A1c by 1-1.5%
 Biguanide derived from Goat’s Rue plant (Glucophage,
Riomet, Glumetza, Fortamet)
 MOA: Decreases hepatic glucose production and
increases insulin sensitivity
 ADR: Diarrhea, B12 deficiency and
 Lactic acidosis
 In 1970s, Phenformin caused cases of Lactic Acidosis
• Onset subtle w/ nonspecific sx incl. malaise, myalgias, resp.
distress, incr. somnolence, nonspecific abdominal distress
• 40-64 cases/100,000 pt-yr
• lead to discontinuation of production in the US
 rare for metformin (~3-9/100,000 pt-yr vs but fatal in
50% of cases
• Risk factors: CRF, sepsis, dehydration, EtOH use, hepatic
insufficiency, >80 y/o and acute/unstable CHF
 Avoid if Cr >1.4 for F, >1.5 for M (some say Ccr <30-
45)

14.  $, Cheap and reduces A1c by 1-
1.5%
 Glipizide (Glucotrol)
 Glyburide (Micronase/Diabeta)
 Glimepiride (Amaryl)
 MOA: Stimulates pancreatic beta
islet cell production
 ADR: hypoglycemia, N/V, anemia
 CKD: dose cut 50%, Avoid
Ccr<50

15.  An 81-year-old male with type 2 diabetes
mellitus has a hemoglobin A1c of 10.9%. He
is already on the maximum dosage of glipizide
(Glucotrol). His other medical problems
include mild renal insufficiency and moderate
ischemic cardiomyopathy.
Which one of the following would be the most
appropriate change in this patient’s
diabetes regimen?
A) Add metformin (Glucophage)
B) Add sitagliptin (Januvia)
C) Add pioglitazone (Actos)
D) Initiate insulin therapy

16.  $-$$, reduces A1c by >2%
 Isolated in the 1920s. Hypoglycemia, edema (wt
gain of 0.5-2.5kg)
 Insulin production
• normal thin healthy person is 18-40 units/day or 0.2-
0.5units/kg
• Type I DM pt ~0.6-0.7units/kg
• Obese ~2units/kg
 50% is Basal, 10-20% per meal is Bolus
 Bolus
• NovoLOG/HumALOG (“LOGarithmic”)
• NovoLIN/HumuLIN R (Regular)
 Basal
• Glargine (Lantus) $$, longer acting
• NPH (NovoLIN/HumuLIN N) $, risk of nocturnal
hypoglycemia

19.  Which one of the following treatments for
diabetes mellitus reduces insulin
resistance?
A) Acarbose (Precose)
B) Sitagliptin (Januvia)
C) Repaglinide (Prandin)
D) Exenatide (Byetta)
E) Pioglitazone (Actos)

20.  $$$
 Pioglitazone (Actos)
 MOA: Increases peripheral
and hepatic sensitivity to
insulin
 Caution with hepatic disease
and contraindicated with CHF
 Rosiglitazone (Avandia) may
increase risk of MI

21.  $$$, reduces A1c by 0.6-0.8%
 MOA: inhibits DPP-4, slowing
incretin metabolism,
increasing insulin synthesis
and release and decreasing
glucagon levels
 Sitagliptin (Januvia)

22.  Which one of the following treatments for
type 2 diabetes mellitus often produces
significant weight loss?
A) Exenatide (Byetta)
B) Glipizide (Glucotrol)
C) Pioglitazone (Actos)
D) Insulin detemir (Levemir)
E) Insulin lispro (Humalog)

23.  $$$, reduces A1c by 1%
 Exenatide (Byetta) 5-10mcg SC
BID, synthetic Gila monster
saliva
 MOA: Stimulate insulin
production in response to
elevated BG levels, inhibit post-
meal glucagon release and slow
nutrient absorption
 Weight loss (but only 4-6# after
30wk)
 ADR: slows gastric emptying,
N/V/D, pancreatitis

24.  Alpha-lipoic acid 600-1800mg daily (B-1)
 Chromium 200-400ug daily (B-2)
 Fish Oil 1-4g daily (B-1)
 Magnesium 300-700mg daily (B-2)
 Vanadium 100-300mg daily (B-2)
 Zinc 15-30mg daily (C-2)
 Vitamin C 1-2 g daily (B-1)
 Bilberry for retinal problems (B-2)
 Ginkgo for vasculopathy (B-1)

25.  Review DM management and challenge
the limits of our repertoire
 Discuss A1c’s role in treatment as a goal
 Review MA, PCHI, ADA and ACE/ACCE
algorithms for treatment
 Discuss most effective, most common and
most economical treatments
 Review EBM
 If we get to it, talk about some
Alternative/Complementary Med

26.  Dynamed “Diabetes Mellitus II” accessed 8/2012
 Essential Evidence Plus “Diabetes Mellitus II” accessed 8/2012
 Salpeter SR., et al. Cochrane Database Syst Rev. 2010 Apr 14;
(4):CD002967. Risk of fatal and nonfatal lactic acidosis with metformin use
in type 2 diabetes mellitus.
 M Stang, et al. Incidence of lactic acidosis in metformin users. Diabetes
care, 1999 - Am Diabetes Assoc
 ABFM In-Training Exam 2011
 David M. Nathan, Judith Kuenen, Rikke Borg, Hui Zheng, David Schoenfeld,
and Robert J. Heine, for the A1c-Derived Average Glucose (ADAG) Study
Group. Translating the hemoglobin A1c assay into estimated average
glucose values. Diabetes Care 2008
 Update on Insulin Management in Type II DM. Journal of Family Practice.
5/2012. Vol 61, No 5.
 Massachusetts Guidelines for Adult Diabetes Care June 2009. Diabetes
Prevention and Control Program.
 PCHI Diabetes Guidelines 2012
 Rakel. Integrative Medicine. 2nd ed. Ch 36. Diabetes.
 Goodman and Gilman. The Pharmacological Basis of Therapeutics, 11 th ed.
Chapter 60 Insulin, oral hypoglycemic agents and the pharmacology of
the endocrine pancreas