1. Drugs for Diabetes Mellitus
Chapter 57
Drugs for Diabetes Mellitus 1

2. Diabetes Mellitus: Overview of the Disease and Its Treatment
Greek word for “fountain”
Latin word for “honey”
Disorder of carbohydrate metabolism
Deficiency of insulin
Resistance to action of insulin
Sustained hyperglycemia, polyuria, polydipsia, ketonuria, and weight loss 2

3. Types of Diabetes Mellitus
Type 1 diabetes
5%–10% of all cases
Also called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes mellitus
Primary defect is destruction of pancreatic beta cells 3

4. Types of Diabetes Mellitus
Type 2 diabetes
Most prevalent form of diabetes
Approximately 22 million Americans have it
Also called non–insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes mellitus
Insulin resistance and impaired insulin secretion 4

5. Complications of Diabetes
Short-term
Hyperglycemia and hypoglycemia
Long-term
Macrovascular damage
Heart disease
Hypertension
Stroke
Hyperglycemia
Altered lipid metabolism 5

6. Complications of Diabetes
Long-term (cont’d)
Microvascular damage
Retinopathy
Nephropathy
Neuropathy
Gastroparesis
Amputation secondary to infection 6

7. Diabetes and Pregnancy
Before insulin: many babies born to severely diabetic women died
Factors during pregnancy
Placenta produces hormones that antagonize the actions of insulin
Production of cortisol increases threefold
Glucose can pass freely from the maternal to the fetal circulation (fetal hyperinsulinemia) 7

8. Diabetes and Pregnancy
Proper glucose levels needed in pregnant patient and in fetus to prevent teratogenic effects
Fetal death frequently occurs near term
Earlier delivery is desirable
Gestational diabetes 8

9. Diagnosis of Diabetes
Excessive plasma glucose is diagnostic of diabetes
Patient must be tested on two separate days, and both tests must be positive
Three tests
Fasting plasma glucose (FPG)
Casual plasma glucose
Oral glucose tolerance test (OGTT)
Hemoglobin A1c, oral glucose tolerance test 9

10. Prediabetes Impaired fasting plasma glucose between 100 and 125 mg/dL
Impaired glucose tolerance test
Increased risk for developing type 2 diabetes
May reduce risk with diet changes and exercise and possibly with certain oral antidiabetic drugs
Many people who meet criteria for “prediabetes” never develop diabetes, even if they do not take precautions against diabetes 10

11. Overview of Diabetes Treatment
Primary goal is to prevent long-term complications
Tight control of blood glucose level is important
Also important to control blood pressure and blood lipids 11

12. Type 1 Diabetes Requires comprehensive plan
Integrated program of diet, self-monitoring of blood glucose, exercise, and insulin replacement
Dietary measures
Total number of carbohydrates, not the type of carbohydrates, is most important
Glycemic index 12

13. Type 2 Diabetes Similar to type 1, requires comprehensive plan
Should be screened and treated for:
Hypertension, nephropathy, retinopathy, neuropathy, dyslipidemias
Glycemic control with:
Modified diet and exercise
Drug therapy 13

14. Monitoring Treatment Self-monitoring of blood glucose (SMBG)
Hemoglobin A1c 14

15. Insulin: Physiology Biosynthesis Secretion Metabolic actions
Metabolic consequences of insulin deficiency 15

16. Seven Types of Insulin Short duration: rapid acting
Insulin lispro (Humalog)
Insulin aspart (NovoLog)
Insulin glulisine (Apidra)
Short duration: slower acting
Regular insulin (Humulin R, Novolin R)
Intermediate duration
Neutral protamine Hagedorn (NPH) insulin
Insulin detemir (Levemir)
Long duration
Insulin glargine 16

17. Insulin Concentration Mixing insulins 100 units/mL (U-100)
NPH with short-acting insulins
Short-acting insulin drawn first 17

18. Administration Subcutaneous injection Subcutaneous infusion
Syringe and needle
Pen injectors
Jet injectors
Subcutaneous infusion
Portable insulin pumps
Implantable insulin pumps (experimental)
Intravenous infusion 18

19. Storage
Unopened vials should be stored under refrigeration until needed
Should not be frozen
Can be used until expiration date if kept in refrigerator
After opening, can be kept up to 1 month without significant loss of activity
Keep out of direct sunlight and extreme heat 19

20. Storage
Mixtures of insulin in vials are stable for 1 month at room temperature and for 3 months under refrigeration
Mixtures in pre-filled syringes should be stored in refrigerator for at least 1 week and should be stored vertically with needle pointing up 20

21. Insulin: Therapeutic Use
Indications
Principal: diabetes mellitus
Required by all type 1 and some type 2 patients
IV insulin for DKA
Hyperkalemia: can promote uptake of potassium
Aids in the diagnosis of GH deficiency 21

22. Insulin Therapy of Diabetes
Dosage
Dosing schedules
Conventional therapy
Intensive conventional therapy
Continuous subQ infusion
Achieving tight glucose control 22

23. Complications of Insulin Treatment
Hypoglycemia
Lipohypertrophy
Allergic reactions
Hypokalemia
Drug interactions
Hypoglycemic agents
Hyperglycemic agents
Beta-adrenergic blocking agents 23

24. Oral Hypoglycemics Biguanides Sulfonylureas
Metformin (Glucophage)
Sulfonylureas
Thiazolidinediones (glitazones)
Rosiglitazone (Avandia)
Pioglitazone (Actos)
Meglitinides (Glinides)
Repaglinide (Prandin)
Nateglinide (Starlix) 24

25. Oral Hypoglycemics Alpha-glucosidase inhibitors Gliptins
Acarbose (Precose)
Miglitol (Glyset)
Gliptins
Combination products 25

26. Combination Products Metformin/Glyburide Metformin/Glipizide
Metformin/Saxagliptin
Metformin/Pioglitazone
Metformin/Repaglinide
Metformin/Sitagliptin
Pioglitazone/Glimepiride
Rosiglitazone/Glimepiride
Rosiglitazone/Metformin
Sitagliptin/Simvastatin 26

27. Injected Drugs (Other than Insulin)
Exenatide
Adjunctive therapy to improve glycemic control in patients with type 2 diabetes
Adverse effects
Hypoglycemia
Gastrointestinal effects
Liraglutide
Pramlintide 27

28. Acute Complications of Poor Glycemic Control
Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmotic nonketotic syndrome (HHNS): Both conditions are hyperglycemic crises
Hyperglycemia is more severe in HHNS
No ketoacidosis in HHNS 28

29. Diabetic Ketoacidosis
Severe manifestation of insulin deficiency
Symptoms evolve quickly in a period of hours or days
Most common complication in pediatric patients and leading cause of death
Characteristics
Hyperglycemia
Ketoacids
Hemoconcentration
Acidosis
Coma 29

30. Diabetic Ketoacidosis
Altered glucose metabolism
Hyperglycemia
Water loss
Hemoconcentration
Altered fat metabolism
Production of ketoacids 30

31. Diabetic Ketoacidosis
Treatment
Insulin replacement
Bicarbonate for acidosis
Water and sodium replacement
Potassium replacement
Normalization of glucose levels 31

32. HHNS Large amount of glucose excreted in urine
Dehydration and loss of blood volume
Increases the blood concentrations of electrolytes and nonelectrolytes (particularly glucose); also increases hematocrit
Blood “thickens” and becomes sluggish 32

33. HHNS Little or no change in ketoacid levels
Little or no change in blood pH
No sweet or acetone-like smell to urine or breath
HHNS occurs most frequently with type 2 diabetes mellitus with acute infection, acute illness, or some other stress 33

34. HHNS
Can evolve slowly
Metabolic changes begin a month or two before signs and symptoms become apparent
If untreated, HHNS can lead to coma, seizures, and death
Management
Correct hyperglycemia and dehydration with IV insulin, fluids, and electrolytes 34

35. Glucagon for Insulin Overdose
Preferred treatment is IV glucose
Immediately raises blood glucose level
Glucagon can be used if IV glucose is not available
Delayed elevation of blood glucose
Will not work in starvation
Promotes glycogen breakdown and the malnourished have little glycogen left 35