Antidiabetic Medications

Pharm 585 February 15, 2011 Hy N Dang

Goal

To understand the use and side effects of antidiabetic medications and be able to educate patients.

Nine to Know
The minimum that every pharmacist must know about drugs!

Brand & Generic Name Mechanism of action Therapeutic effect Relevant pharmacokinetics and pharmacodynamics Dosing by route Adverse reactions and contraindications Monitoring parameters Drug-drug and drug food interactions Comparisons between agents w/in the same class of drugs

Contraindications/Cautions/Adver se Reactions

Adverse Reactions

Unwanted side effects: need to warn patient Warnings for clinicians to be aware when using medication. Conditions which will render the medication absolutely unusable in that patient population

Cautions

Contraindications

Type 2 Diabetes
High blood glucose Impaired GI motility

1. Defective beta cell function

Diminished phase 1 insulin release Delayed phase 2 insulin release

2. Overproduction of glucagon

1. Tissues less sensitive to insulin 2. Liver produces excess glucose

Image Obtained From: Diabetes 101: Overview of Drug Therapy by Jennifer Danielson, RPh, CDE

Type 2 Video from diabetes.com

Biguanides
Metformin Glucophage (Glucophage XR) 500, 850, 1000 mg 500, 750 mg XR tablets tablets

Indication Type II Diabetes Mellitus, Antipsychotic-induced weight gain MOA Decrease hepatic glucose production, decrease intestinal absorption of glucose and increase insulin sensitivity therefore increasing peripheral glucose uptake

Where does it work?

Image Obtained From: Diabetes 101: Overview of Drug Therapy by Jennifer Danielson, RPh, CDE

Biguanides (cont)
Patient Info N/V/D Upset stomach/dyspepsia take with food Metallic taste Minimal Weight Loss Alcohol may increase likelihood of lactic acidosis Does not cause hypoglycemia

Biguanides (cont)
Special Population Considerations: Geriatric: limited data suggests starting doses should be 33% lower for geriatric patients than that of an adult dose. Titration should also to a lower limit. Cautions/Severe Adverse Reactions Black Box Lactic Acidosis: D/C immediately and notify practitioner if: myalgia, malaise, hyperventilation, unusual somnolence. Alcohol potentiates this reaction. Advise patients not to consume excessive amounts of alcohol.

Biguanides (cont)
CONTRAINDICATIONS Renal disease or renal dysfunction (Scr > 1.5 mg/dL in males, >1.4 mg/dL in females) Abnormal Scr from any cause including: shock, acute MI, or septicemia Metabolic acidosis (including diabetic ketoacidosis (DKA)) Heart failure requiring pharmacologic therapy; active liver failure

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors

Sitagliptin Sitagliptin/metformin Saxagliptin (Januvia) (Janumet) (Onglyza) 25, 50, 100 mg 50/500, 50/1000 mg 2.5, 5 mg tablets tablets tablets

Saxagliptin/metformin

(Kombiglyze XR)

2.5/1000, 5/500, 5/1000 mg

tablets

Indications Diabetes Mellitus Type II MOA Inhibits the breakdown of GLP-1 by DPP-4 therefore increasing GLP-1 levels resulting in increased glucose-dependent insulin release and decreased level of circulating glucagon and hepatic glucose production

Where does it work?

Image Obtained From: Diabetes 101: Overview of Drug Therapy by Jennifer Danielson, RPh, CDE

DPP-4 (cont)
Patient Info N/V Hypoglycemia Weight neutral Nasopharyngitis/URI Headache Onset: Reduction in postprandial serum glucose: 60 minutes

DPP-4 (cont)
Special Population Considerations: Renal Impairment: avoid combo drugs w/ metformin For sitagliptin: CrCl 30-50 mL/min : 50 mg daily CrCl < 30 mL/min: 25 mg daily End Stage Renal Disease Requiring dialysis: 25 mg daily Geriatric: caution due to age related renal function decreases Cautions/Severe Adverse Reactions Acute pancreatitis Rash (Stevens-Johnson syndrome)

Sulfonylureas
Glimepiride Glipizide Glyburide Indications Adjuncts to diet and exercise to lower blood glucose in patients w/ type II diabetes mellitus MOA Stimulating insulin release from beta-cells of pancreatic islets (Amaryl) (Glucotrol, Glucotrol XL) (DiaBeta) 1, 2, 4 mg (2.5), 5, 10 mg (XL) 1.25, 2.5, 5 mg tablets tablets tablets

Where does it work?

Image Obtained From: Diabetes 101: Overview of Drug Therapy by Jennifer Danielson, RPh, CDE

Sulfonylureas (cont)
Patient Info

Hypoglycemia GI upset/abdominal pain Dizziness Weight gain Heartburn/epigastric fullness Possible disulfiram-like reaction with alcohol (mainly w/ glyburide) Onset: glucose lowering effect: 30 minutes with peak at 1.5-3 hours lasting 24 hours

Sulfonylureas (cont)
Special Population Considerations: Pediatric: safety and efficacy not established for pts under age 16 Hepatic/Renal Dysfunction: conservative dosing and titration recommended. Caution/Severe Adverse Reactions Syndrome of Inappropriate Anti-diuretic Hormone (SIADH) CONTRAINDICATIONS Diabetes complicated by ketoacidosis Type I DM Diabetes w/ pregnancy. Pregnancy Cat: C (except glyburide: B)

Thiazolidinediones (TZD)
Pioglitazone Rosiglitazone (Actos) (Avandia) 15, 30, 45 mg 2, 4, 8 mg tablets tablets

Indications As adjunct to diet and exercise for type II diabetes MOA Increase insulin sensitivity by affecting PPAR- (peroxisome proliferators-activated receptor) at adipose tissue, skeletal muscle and in the liver. Special Alert February 2011: Addition of Risk Evaluation and Mitigation Strategy to rosiglitazone. The medication is restricted to those patients already on rosiglitazone for fails pioglitazone or cannot be managed by other oral antidiabetic medications.

Where does it work?

Image Obtained From: Diabetes 101: Overview of Drug Therapy by Jennifer Danielson, RPh, CDE

TZD (cont)
Patient Info Weight gain Edema Hypoglycemia esp. when used with other antidiabetic medications and insulin (not w/ metformin) May cause or exacerbate heart failure with risk of fluid retention URI, sinusitis, pharyngitis Myalgia Headache

TZD (cont)
Cautions/Severe Adverse Reactions Black Box: Heart Failure (for all thiazolidinediones, mainly due to rosiglitazone) Hepatic failure Anemia Bone loss Ovulation in premenopausal women Pregancy Cat: C

TZD (cont)
Special Populations Considerations: Congestive Heart Failure: should be initiated at lowest approved dose with longer intervals between dose increases for NYHA class II. Use is not recommended in patients with NYHA Class III or IV CHF CONTRAINDICATIONS NYHA Class III-IV heart failure Active liver disease (ALT > 2.5 upper limit of normal)

Insulin
Indications Type I diabetes mellitus, type II diabetes mellitus, hyperkalemia, DKA/diabetic coma MOA Stimulating peripheral glucose uptake and inhibiting hepatic glucose production

Patient Info Hypoglycemia (BG < 70 mg/dL) esp with higher doses Anxiety, blurred vision, palpitations, shakiness, slurred speech, sweating Weight gain

Where does it work?

Image Obtained From: Diabetes 101: Overview of Drug Therapy by Jennifer Danielson, RPh, CDE

Insulin: the Movie from diabetes.org

Insulin (cont)
Administration: Subcutaneous injection Rotate site Check blood sugars regularly Storage: Refrigerate until use Once vial is punctured, it is good for 28 days and can be left at room temperature (except for glargine which is 90 days)

Insulin (cont)
Dosing: Starting daily dose: 0.5-1 unit/kg/day in divided doses Adjust according to fasting (premeal) blood glucose of 80-130 mg/dL and peak postprandial blood glucose < 180 mg/dL Provide 50% as long acting insulin and 50% as prandial insulin 1 unit of can account for 30 grams of carbohydrate (14-50) 1 unit can lower 50 mg/dL blood glucose (10-100) Special Population Consderations: Renal dysfunction

CrCl 10-50 mL/min: 75% of normal dose CrCl < 10 ml/min: 25-50% of normal dose; monitor closely

Exercise??? ---- Acute Stress???

Insulin Action

Rapid/immediate

Blood concentration

Intermediate

Fast Slow

10

12

14

16

18

20

22

24

Time (hr)

Insulin Dosing
Long-acting

Long-acting & Short-acting

Normal insulin secretion

70/30 pre-mixed

Insulin Administration

Pharmacology for Technicians by Ballington, Lauglin. EMC Paradigm 2006, Fig. 14.9

Insulin (cont)
Cautions/Severe Adverse Reactions Severe hypoglycemia (seizure/coma) (BG < 40 mg/dL) Edema Lipoatrophy or lipohypertropy at injection site CONTRAINDICATIONS Severe hypoglycemia Allergy or sensitivity to any ingredient of the product

Insulin Comparison Chart

courses.washington.edu/pharm504/Insulin%20Chart.pdf

Adjunctive Therapy in Diabetes Mellitus Type II

Hypoglycemia

Complication of treatment! Make sure patients inform the people around them of these symptoms and what to do! Symptoms: Anxiety, blurred vision, palpitations, shakiness, slurred speech, sweating Treatment: glucose/simple sugars: 3-4 glucose tablets, can of soda (NOT diet!) Treatment: glucagon injection

Dose: 1 mg IM, IV, SQ; may repeat in 20 minutes if needed

Adjunctive Therapy (cont)

Energy balance, diet, exercise Low-carb, low-fat, calorie-restricted diet is recommended

Cardiovascular disease/Hypertension Systolic blood pressure goal < 130 mm Hg Angiotensin Converting Enzyme II Inhibitor (ACE-I) is first line Renal protective Angiotensin Receptor Blockers (ARB) can be used if patient fails or is intolerant to ACE-I

Adjunctive Therapies (cont)

Dislipidemia Patients with type II diabetes have an LDL goal < 100 mg/dL Weight loss First line therapy: statins (i.e. atorvastatin, simvastatin, rosuvastatin etc.) Fiber, omega-3 fatty acids (fish oils) can be used as adjunct therapy Antiplatelet agents Consider starting daily low dose aspirin (81 mg) to prevent ischemic events

Adjunctive Therapies (cont)

Smoking cessation Regular Screening for Cardiovascular Diseases and Coronary Artery Disease Depression/Stress/Anxiety/Other psychosocial conditions need to be screen for regularly Diabetic neuropathies especially in extremities need to be screened for on a regular basis

Fastidious foot care Regular foot exams (annually)

Eye exams Monitor kidney function