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Oral Diabetes Medications. Carol Cordy, MD Swedish Family Practice Residency January 14, 2003. 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

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Oral diabetes medications
Oral Diabetes Medications

Carol Cordy, MD

Swedish Family Practice Residency

January 14, 2003


Goals
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


Progression of type 2 diabetes
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


Organs affected in diabetes

Pancreas and Liver

Muscle and Fat

Organs Affected in Diabetes


Insulin resistance
Insulin Resistance

Muscle = Postprandial Hyperglycemia

Fat = Increased FFA Concentration and Hepatic VLDL-TG


Increased Liver Glucose Production = Increase in Fasting Hyperglycemia

  • b-Cell Dysfunction = Decrease in Insulin Production


Insulin resistance and type 2 diabetes
Insulin Resistance and Hyperglycemia 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


Classes of oral medications
Classes of Oral Medications Hyperglycemia

  • 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)


Uk study 1998
UK Study - 1998 Hyperglycemia

Traditional glycemic control (secretagogues)

reduced microvascular complications

  • Retinopathy -29%

  • Nephropathy -33%

  • Neuropathy -40%

    But not macrovascular complications

  • MI’s -16%

  • Stroke +11%

  • Deaths -6%


Uk study 19981
UK Study 1998 Hyperglycemia

Metformin decreased macrovascular

complicatons (lower insulin levels)

  • MI -39%

  • Coronary Deaths -50%

  • Diabetes Related

    Deaths -42%

  • All Cause Mortality -36%


First line drug for type 2 diabetes
First Line Drug for Type 2 Diabetes Hyperglycemia

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)


Second line drugs for 2 type diabetes
Second Line Drugs for Hyperglycemia 2 Type Diabetes

Thiazolidinediones (Glitazones)

Increase muscle uptake of glucose, decrease FFA, increase HDL’s, decrease triglycerides, may cause weight gain and edema, may increase LFT’s, 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 LFT’s, cause flatulance


Tripod study 2001
Tripod Study Hyperglycemia - 2001

  • Troglitazone prevented the development of diabetes in patients with a history of gestational diabetics (age 35, BMI 30)

    by 54%

  • Early treatment withb-cell rest may delay onset of diabetes

  • Thiazolidinediones may be more effective than metformin in prevention and treatment of diabetes


Insulin resistance1
Insulin Resistance Hyperglycemia

Muscle = Postprandial Hyperglycemia

Fat = Increased FFA Concentration and Hepatic VLDL-TG


Increased Liver Glucose Production = Increase in Fasting Hyperglycemia

  • b-Cell Dysfunction = Decrease in Insulin Production


Progression of type 2 diabetes1
Progression of Hyperglycemia 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


One approach to selecting medication for type 2 diabetics
One Approach to Selecting Medication for Type 2 Diabetics Hyperglycemia

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


Affect on blood glucose
Affect on Blood Glucose Hyperglycemia

  • Reduce fasting glucose – metformin and sulfonylureas

  • Reduce postprandial glucose – meglitinides and a-glucosidase inhibitors

  • Reduce fasting and postprandial glucose - glitazones


Goal for glycemic control
Goal for Glycemic Control Hyperglycemia

  • 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)


Case 1
Case #1 Hyperglycemia

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?


Test results
Test Results Hyperglycemia

  • HbA1C 9.2

  • Alb/Cr 0.010

  • Cr 0.6

  • LFT’s WNL

  • CBC WNL

  • TSH 2.3

  • Fasting Insulin

    C-peptide 3.5

    b-HCG Neg


What will you do now
What will you do now? Hyperglycemia

  • 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


Anything else
Anything else? Hyperglycemia

  • 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


Eight months later
Eight Months Later Hyperglycemia

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. LFT’s remain normal.

What would you do now?


Second oral medication
Second Oral Medication Hyperglycemia

Add a

  • Glitazone or

  • Sulfonylurea


Summary
Summary Hyperglycemia

  • 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


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