Oral Diabetes Medications

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Oral Diabetes Medications

• Carol Cordy, MD
• Swedish Family Practice Residency
• January 14, 2003

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Goals

• Understand how type 2 diabetes affects many
  organs and how this changes over the course of
  the illness
• Understand how each class of oral diabetes
  medications works
• Using the above, be able to pick the best
  medication or combination of medications for our
  patients with type 2 diabetes

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Progression of Type 2 Diabetes

• OGTT Insulin Glu uptake
• mg/dL uU/mL mg/m2xmin
• Normal 100 80 70
• Glu Intol 150 140 30
• DM - HI 250 100 20
• DM - LI 350 20 20

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Organs Affected in Diabetes

• Muscle and Fat

• Pancreas and Liver

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Insulin Resistance

• Muscle Postprandial Hyperglycemia
• Fat Increased FFA Concentration and Hepatic
  VLDL-TG

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• Increased Liver Glucose Production Increase
  in Fasting Hyperglycemia
• b-Cell Dysfunction Decrease in Insulin
  Production

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Insulin Resistance and Type 2 Diabetes

• 40 of older people are insulin resistant mostly
  secondary to obesity and inactivity (important in
  prevention and treatment)
• 20 of the elderly have type 2 diabetes
• 8.5 of all adults have type 2 diabetes
• 90 of diabetics are managed in primary care

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Classes of Oral Medications

• Drugs that help the body use insulin
  (sensitizers)
• Drugs that stimulate the pancreas to release more
  insulin (secretagogues)
• Drugs that block the breakdown of starches and
  sugars (a-glucosidase inhibitors)

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UK Study - 1998

• Traditional glycemic control (secretagogues)
• reduced microvascular complications
• Retinopathy -29
• Nephropathy -33
• Neuropathy -40
• But not macrovascular complications
• MIs -16
• Stroke 11
• Deaths -6

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UK Study 1998

• Metformin decreased macrovascular
• complicatons (lower insulin levels)
• MI -39
• Coronary Deaths -50
• Diabetes Related
• Deaths -42
• All Cause Mortality -36

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First Line Drug for Type 2 Diabetes

• Biguanide
• Metformin (Glucophage and Glucophage XR)
• Decreases hepatic glucose output
• Increases insulin sensitivity
• Decreases LDL and triglycerides
• Decreases C-reactive protein
• Causes weight loss or stabilization
• No risk of hypoglycemia
• Causes nausea, cramps and diarrhea
• Lactic acidosis rare (contraindications
• CHF, renal impairment, age greater than 80)

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Second Line Drugs for 2 Type Diabetes

• Thiazolidinediones (Glitazones)
• Increase muscle uptake of glucose, decrease FFA,
  increase HDLs, decrease triglycerides, may cause
  weight gain and edema, may increase LFTs,
  decrease C-reactive protein
• Sulfonylureas and Meglitinides
• Increase pancreatic insulin release, cause
  weight gain and hypoglycemia
• a-Glucose Inhibitors
• Decrease absorbtion of carbohydrates in the
  small intestine, increase LFTs, cause flatulance

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Tripod Study - 2001

• Troglitazone prevented the development of
  diabetes in patients with a history of
  gestational diabetics (age 35, BMI 30)
• by 54
• Early treatment with b-cell rest may delay onset
  of diabetes
• Thiazolidinediones may be more effective than
  metformin in prevention and treatment of diabetes

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Insulin Resistance

• Muscle Postprandial Hyperglycemia
• Fat Increased FFA Concentration and Hepatic
  VLDL-TG

15

• Increased Liver Glucose Production Increase
  in Fasting Hyperglycemia
• b-Cell Dysfunction Decrease in Insulin
  Production

16
Progression of Type 2 Diabetes

• OGTT Insulin Glu uptake
• mg/dL uU/mL mg/m2xmin
• Normal 100 80 70
• Glu Intol 150 140 30
• DM - HI 250 100 20
• DM - LI 350 20 20

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One Approach to Selecting Medication for Type 2
Diabetics

• Check a fasting insulin C-peptide level
• If high or high-normal use an insulin sensitizer
  biguanine or glitazone or a combination of the
  two
• If low or low-normal use an insulin secretagogue
• Consider changing patients who were put on
  insulin before the new oral diabetes medications
  to insulin sensitizers

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Affect on Blood Glucose

• Reduce fasting glucose metformin and
  sulfonylureas
• Reduce postprandial glucose
  meglitinides and a-glucosidase inhibitors
• Reduce fasting and postprandial glucose -
  glitazones

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Goal for Glycemic Control

• HbA1C less than 7 (6.5?)
• Fasting sugars less than 110
• Two-hour postprandial sugars
• less than 140
• Blood pressure less than 130/80 (125/75 if renal
  impairment)

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Case 1

• 30 y.o. woman with a history of gestational
• diabetes with her first pregnancy at age 21
• presents with frequent urination, thirst, weight
• loss and a random glucose of 250. She has an
• IUD in place. Her BMI is 33. BP is 140/80.
• Is this enough information to diagnose diabetes?
• What other tests would you order?

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Test Results

• HbA1C 9.2
• Alb/Cr 0.010
• Cr 0.6
• LFTs WNL
• CBC WNL
• TSH 2.3
• Fasting Insulin
• C-peptide 3.5
• b-HCG Neg

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What will you do now?

• Educate your patient about diabetes and set goals
  together for her care
• Refer to a nutritionist for diabetic diet
  counseling and a weight loss program
• Refer to a diabetes educator for education in use
  of a glucose meter
• Refer to PT for an exercise program

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Anything else?

• Refer to ophthalmologist
• Do microfilament check for neuropathy
• See frequently to reinforce diet, exercise, home
  glucose monitering
• Start Metformin XL
• Treat BP with ACEI if remains over 130/80

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Eight Months Later

• Despite modest weight loss and compliance with
  her medications your patient still has a HbA1C of
  8.0. Her blood pressue is 120/75 and her Alb/Cr
  is 0.012. LFTs remain normal.
• What would you do now?

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Second Oral Medication

• Add a
• Glitazone or
• Sulfonylurea

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Summary

• Type 2 diabetes affects many organs
• Type 2 diabetes changes over time
• Diabetes treatment changes over time
• Medications can now be selected to work where the
  problem is
• Combinations of medications, because they work at
  different sites, in the body usually work better
  than monotherapy