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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

insulin resistance
Insulin Resistance

Muscle = Postprandial Hyperglycemia

Fat = Increased FFA Concentration and Hepatic VLDL-TG

slide6
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 199810
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 resistance14
Insulin Resistance

Muscle = Postprandial Hyperglycemia

Fat = Increased FFA Concentration and Hepatic VLDL-TG

slide15
Increased Liver Glucose Production = Increase in Fasting Hyperglycemia
  • b-Cell Dysfunction = Decrease in Insulin Production
progression of type 2 diabetes16
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

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-HCG Neg

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