Management of Type 2 Diabetes: Stuff Youve Gotta Know

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Management of Type 2 DiabetesStuff Youve
Gotta Know

• Robert Sidlow, M.D.
• Associate Medical Director, North Bronx HCN
• Assistant Professor of Medicine, AECOM

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The Truth

• Type 2 DM results in pancreatic beta cell failure
  in most patients (sounds like type 1!)

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The Implication

• In order to reach A1C goals, type 2 diabetics
  will eventually need exogenous insulin.

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What is the evidence that adding insulin to OAD
regimens actually works?
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FINFAT Ann Int Med. 130389-396, 1999.

• RCT
• 94 type 2 diabetics, mean A1c9.9
• Intervention
• NPH glyburide (10 mg/d)
• NPH Metformin (1 gm BID)
• NPH glyburide metformin
• NPH (AM) NPH (PM)
• Bedtime NPH was self-titrated via simple
  algorithm to pre-breakfast glucose of 108 mg/dl
• One year long

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Results at 12 months

• Doses of NPH were between 30 to 40 units/day
• A1C dropped the most in the NPHmetformin group
  (average 7.2)
• No weight gain in NPHmetformin group, as opposed
  to 4kg gain in other groups

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Hypoglycemic Episodes

• Mean of symptomatic episodes/patient
• Insulin glyburide 3.4
• Insulin glyburide metformin 3.3
• Insulin Insulin 3.9
• Insulin Metformin 1.8
• None of the episodes were severe defn
  requiring intervention from another person

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FINFAT-The Bottom Line

• Adding NPH to any OAD regimen improves glycemic
  control
• NPH plus Metformin (1 gram BID) resulted in best
  glycemic control, least weight gain, and fewest
  hypoglycemic episodes
• Insulin self-titration via algorithm is safe and
  effective

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What About Post-Prandial Glucose Excursion?
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Post-Prandial Glucose Excursion is Important!

• But is not addressed by long acting insulins,
  which mainly deal with fasting plasma glucose
  levels (basal)
• Affects the A1C
• Is an independent RF for micro and macro vascular
  complications of DM

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• In patients with elevated HgbA1C despite good
  fasting (pre-breakfast) fingersticks, consider
  post prandial hyperglycemia as the cause.
• In such cases check 2 hr post-meal glucose. If
  gt200 consider adding short acting insulin or
  changing to a split 75/25 or 70/30 insulin mix.

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OAD Failureobservations

• If a patient is on two oral agents and the A1C is
  8 or more, adding a third agent will probably
  not get you to target!
• Diet and exercise produce at most a 1 reduction
  in A1C maximum effect is at 3 months.
• We under-insulinize our type 2 diabeticstoo
  little and too late.

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OAD Failuresuggestions

• If the A1C is between 7-8 consider adding a
  third oral agent or insulin.

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OAD Failuresuggestions

• If the A1C is 8 or greater, ADD a bedtime shot
  of insulin with the self-titration algorithm.
• Choice of NPH vs. glargine is up to you
• Reduced hypoglycemic episodesclinically
  relevant?
• Cost considerations
• Excellent delivery devices for NPH

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OAD Failurewhat to do (cont)

• If the A1C remains above target despite two to
  three months of bedtime insulin, address
  post-prandial glucose excursions with AM and PM
  split dose of NovoLog Mix 70/30 (aspart
  protamine/aspart) or Humalog 75/25 (lispro
  protamine/lispro)

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Delivery Devices

• Innolet-NovoNordisk
• Pre-filled with NPH
• Disposable, self contained
• Easy to dose with large dial
• Come in package of 5 1500 u
• Covered by MCD

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Delivery Devices

• FlexPen- NovoNordisk
• Pre-filled with 70/30 (aspart protamine/aspart)
• Disposable, self contained
• Convenient
• Come in package of 5 1500 units
• Covered by MCD

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Perceived Barriers

• Pain
• Tiny 30 and 31 gauge needles
• Less painful than glucose monitoring pricks
• Can demonstrate on self or student
• Inconvenient
• Once opened do not need to be refrigerated
• Disposable
• Difficult to Use
• Easier than syringe and vials
• Weight gaininevitable

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Self- Titration Algorithm

• On jacobimed.org website

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A few words about oral agents-

• Monotherapy is doomed to failure!

UKPDS Data A1Clt 7 at 9 years
JAMA 28120051999
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A few words about oral agents-Metformin

• Consider using metformin as the first-line agent
  in obese patients
• UKPDS data suggests decreased CV events in
  metformin-treated patients
• GI side effects abate with time. Start low,
  titrate up weekly.

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A few words about oral agents-Dosing

• Maximal therapeutic effects are found at
  sub-maximal doses of SFU and metformin
• No extra benefit is gained by increasing
  glyburide 10 mg daily to 10 mg BID or metformin
  2000 mg daily to 2550 mg daily

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PPAR Gamma Agonists-glitazones

• Glycemic control efficacy (1 A1c decrease) and
  safety well established
• Intriguing anti-inflammatory and
  endothelium-stabilizing activity

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Pioglitazone- the bottom line PROactive

• As add-on therapy in high risk patients,
  pioglitazone decreases MI, stroke, and death
  (slight marginal benefit).
• Pioglitazone delays onset of need for conversion
  to insulin.
• Beware of weight gain, edema, and precipitating
  HF in decompensated CHF

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New Stuff
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It turns out that the gut talks to the pancreas
and brain via Incretins!
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• GLP-1 is responsible for 60 of pancreatic
  insulin secretion in response to a meal!!

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GLP-1 Solution 1

• Lizard Spit
• Exenatide (Byetta) first identified in the saliva
  of the Gila Monster
• 50 homology to GLP-1incretin mimetic
• Much longer half life
• than GLP-1

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Exenatide

• 10 mcg sq twice daily
• Approved for use as adjunct to metformin and/or
  SFU
• Nausea common

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GLP-1 Solution 2

• Inhibit the GLP-1 degrading enzyme DPP-IV
• GLIPTINS

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Traditional Stepped-Care
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Paradigm shift

• Movement to early, aggressive pathophysiology-targ
  eted combined therapy with TZD (muscle and
  adipose insulin resistance) and metformin (liver
  fasting gluconeogenesis)
• Earlier use of insulin in patients who dont
  reach their target
• Base medication regimen upon severity of
  diseaseStratified Care

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2003 Canadian Diabetes Association
Guidelines http//www.diabetes.ca/cpg2003/download
s/pharmacologic.pdf
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Dont forget about the other CVD risk factors!

• Hypertension
• Dyslipidemia
• Smoking

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Hypertension- A.D.A. Treatment Goals
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HPS Main Conclusions

• Simvastatin 40 mg/day safely reduces the risk of
  heart attack, of stroke, and of revascularisation
  by at least one-third in at-risk patients
• For every 14 type 2 diabetics treated with 40 mg
  of simvastatin, one coronary event was prevented.

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• Recent findings from the Heart Protection
  Study, in people with diabetes over the age of 40
  years with a total cholesterol 135 mg/dl,
  suggest that statin therapy to achieve an LDL
  reduction of 30 regardless of baseline LDL
  levels may be appropriate.
• -American Diabetes Organization Clinical
  Practice recommendations, January 2004

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Final Point

• A little DM
• Some sugar
• Its just 8
• Keep HbA1c lt 7!

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