Oral diabetes medications
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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

OGTTInsulinGlu uptake

mg/dLuU/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


Oral diabetes medications

Increased Liver Glucose Production = Increase in Fasting Hyperglycemia

  • b-Cell Dysfunction = Decrease in Insulin Production


Insulin resistance and type 2 diabetes

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


Classes of oral medications

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)


Uk study 1998

UK Study - 1998

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

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

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 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- 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

Muscle = Postprandial Hyperglycemia

Fat = Increased FFA Concentration and Hepatic VLDL-TG


Oral diabetes medications

Increased Liver Glucose Production = Increase in Fasting Hyperglycemia

  • b-Cell Dysfunction = Decrease in Insulin Production


Progression of type 2 diabetes1

Progression of Type 2 Diabetes

OGTTInsulinGlu uptake

mg/dLuU/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

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

  • 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

  • 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

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

  • 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-HCGNeg


What will you do now

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


Anything else

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


Eight months later

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. LFT’s remain normal.

What would you do now?


Second oral medication

Second Oral Medication

Add a

  • Glitazone or

  • Sulfonylurea


Summary

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


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