Management of new type II diabetes diagnosis

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Management of new type II diabetes diagnosis

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Case

• 31yr old healthy black man who presents to clinic
  with polyuria and polydipsia, small amount of
  weight loss.
• Family history DM in grandmothers
• Social history loves fried chicken, macaroni and
  cheese, and sweet tea. Works in the receiving
  dock at UNC.
• PE BMI 31, BP 142/82, P 102, FSBG 437
• Obese black man, otherwise normal exam.

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Case

• Labs
• Chem profile normal except glucose 430.
• Hgb A1C 16.2
• Plan
• Diet modification!
• Oral therapy vs insulin?
• How many agents?

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Overview

• Oral diabetes medications
• Injectible diabetes medications
• Average Hgb A1C reduction with monotherapy
• Study discussion rosiglitazone vs glyburide vs
  metformin monotherapy.
• New diabetes diagnosis algorithms

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Diabetes medications

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Diabetes Medications
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New class

• DPP-4 inhibitors sitagliptin (Januvia).
• DPP-4 is the enzyme which breaks down incretins.
• Drug results in increased insulin release and
  decreased glucagon release.

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Insulin therapy

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Hgb A1C reduction at maximum dose

• Sulfonylureas 1.0-2.0
• Meglitinides 1.1
• Metformin 1.4
• Rosiglitazone 0.1-0.7
• Pioglitazone 0.3-0.9
• Alpha-glucosidase inhibitors 0.5-1.0
• AACE Diabetes Guidelines, 2002

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Glycemic Durability of Rosiglitazone, Metformin,
or Glyburide Monotherapy

• NEJM Dec 7, 2006

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Study set-up

• 4360 patients followed over a median of 4.0
  years.
• Double-blind, randomized trial
• 3 groups rosiglitazone, metformin, and glyburide
  monotherapy
• Primary outcome Time to monotherapy failure
  (i.e. fasting plasma glucose of more than
  180mg/dl after 6weeks on maximum dose.)

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Study population

• Mostly middle aged 50s (range 30-75)
• Over half patients were men (55-60)
• Almost all white (88)
• Fasting glucose at initiation 126-180mg/dl
• Average Hgb A1C 7.36
• Average BMI 32
• Excluded liver disease, renal failure, hx lactic
  acidosis, unstable/severe angina, CHF (any
  stage), uncontrolled hypertension.

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Primary outcome monotherapy failure

• Rosiglitazone 143 patients 15 at 5yrs
• Metformin 207 patients 21 at 5yrs
• Glyburide 311 patients 34 at 5yrs
• RRR rosiglitazonemetformin 32 (? Bias ?)
• RRR rosiglitazoneglyburide 63
• At time of treatment failure, 99 patients on
  maximum dosage of drug.

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Secondary outcomes

• Hgb A1C
• Rosiglitazone group 40
• Metformin 36
• Glyburide 26
• Beta cell function (as measured by HOMA)
• Increased in glyburide group in the 1st 6 months
  (but then declined).
• Declined least overall in the rosiglitazone
  group only 2

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Weight changes

• Increased in rosiglitazone group 4.8kg
• Decreased in metformin group -2.9kg
• Increased initially in glyburide, then remained
  stable 1.6kg

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Adverse outcomes

• Rosiglitazone more edema, decreased hematocrit,
  higher LDL, ?fracture
• Metformin more GI side effects
• Glyburide more hypoglycemia, increases in ALT,
  weight gain

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Problems with the study

• Primary endpoint fasting blood glucose
  measurement
• High drop-out rate without intention to treat
  analysis
• 63 finished in the rosiglitazone group
• 62 in the metformin group
• 56 in the glyburide group
• Bias could not be excluded in the comparison of
  rosiglitazone to metformin.
• Sponsorship by GlaxoSmithKline

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Summary

• Consider rosiglitazone as initial monotherapy for
  patients with new diabetes.
• Consider side effect profiles when choosing
  initial therapy.
• Even with low starting Hgb A1C levels,
  monotherapy failure is frequent.

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Questions that remain to be answered

• At what point do you add insulin?
• Is there a best initial monotherapy?
• Is there a best initial combination therapy?

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Diabetes Algorithms

• UNC New Diabetes Diagnosis algorithm
• http//www.med.unc.edu/medicine/generalm/enhancedc
  are.html
• American Diabetes Association algorithm
• http//care.diabetesjournals.org/cgi/content/full/
  30/suppl_1/S4/F1

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References

• American Diabetes Association website
  www.diabetes.org.
• American Association of Clinical Endocrinologists
  website www.aace.com.
• Kahn, S, et.al. Glycemic durability of
  rosiglitazone, metformin, or glyburide
  monotherapy. N Engl J Med 2006 355 2427-43.
• Sicat, BL, LA Morgan. New therapeutic options
  for the management of diabetes. Consult Pharm.
  2007 Jan 22(1) 45-56.
• AACE Diabetes Guidelines, Endocr Pract. 2002
  8(suppl 1).