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Antidiabetic Medications

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

Biguanides
Metformin 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 Depends upon Power Dosing Presence of insulin Decreases HbA1c 1% to 2% One to three times daily Glucophage Glucophage XR 500, 850, 1000 mg 500, 750 mg XR tablets tablets

Biguanides
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
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
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

Sulfonylureas

Tolbutamide

Acetohexamide

Tolazamide

Chlorpropamide

Sulfonylureas

Glyburide

Glipizide

Glimepiride

Sulfonylureas
Glimepiride Glipizide Glyburide Amaryl Diamicrom, Diamicrom XL) (DiaBeta) 1, 2, 4 mg (2.5), 5, 10 mg (XL) 1.25, 2.5, 5 mg tablets tablets tablets

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 Onset glucose lowering effect: 30 minutes with peak at 1.5-3 hours lasting 24 hours

Sulfonylureas

SU
sulphonylurea receptor

KATP channel
pancreatic beta cell insulin

SU

KATP channel closes

membrane depolarisation

SU
Ca2+ calcium entry Ca2+ insulin insulin secretion insulin

@ Sulphonylureas allow for insulin release at lower glucose threshold

Sulfonylureas


Adverse Effects

Contraindications

Hypoglycemia Nausea and vomiting Cholestatic jaundice Agranulocytosis Anemia Hypersensitivity Dermatological rxns Drug interactions Dizziness Weight gain

Type I diabetes Pregnancy/lactation Hepatic/renal failure Diabetes complicated by ketoacidosis

Sulfonylureas
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)

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors


Vildagliptin Galvus 50 mg 50/500, 50/1000 mg 25, 50, 100 mg 50/500, 50/1000 mg 2.5, 5 mg tablets tablets tablets tablets tablets Tablets

Vildagliptin/metformin Galvusmet Sitagliptin Sitagliptin/metformin Saxagliptin (Januvia) (Janumet) (Onglyza)

Saxagliptin/metformin (Kombiglyze 2.5/1000, 5/500, XR) 5/1000 mg

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors


   

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

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

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors


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)

GLP-1 receptor agonist


Liraglutide Exenatide   Victoza Byetta Once daily Once daily Injection Injection

It is 97% similar to endogenous GLP-1 (7-37). It provides powerful and sustained reductions in A1C for adults with type 2 diabetes and has direct and indirect effects in multiple organ systems that affect glucose homeostasis

GLP-1 receptor agonist


     

It slows gastric emptying It reduces glucagon secretion, helping to lower hepatic glucose output from the liver It impacts beta-cell function and improves insulin secretion in the pancreas Structural modifications increase the stability against DPP-4 and promote plasma protein binding. 13-hour half-life because an amino acid substitution and a fatty acid attachment make it stable against degradation by DPP-4. suitable for once-daily administration.

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.

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

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