Antidiabetic Medications

Goal

To understand the use and side effects of anti-

diabetic 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
 Cautions
– Warnings for clinicians to be aware when using
medication.
 Contraindications
– Conditions which will render the medication
absolutely unusable in that patient population
 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 500, 850, 1000 mg tablets

(Glucophage XR) 500, 750 mg XR 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 (Januvia) 25, 50, 100 mg tablets

Sitagliptin/metformin (Janumet) 50/500, 50/1000 mg tablets
Saxagliptin (Onglyza) 2.5, 5 mg tablets
Saxagliptin/metformin (Kombiglyze 2.5/1000, 5/500, tablets
XR) 5/1000 mg

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 (Amaryl) 1, 2, 4 mg tablets

Glipizide (Glucotrol, (2.5), 5, 10 mg tablets
Glucotrol XL) (XL)
Glyburide (DiaBeta) 1.25, 2.5, 5 mg 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

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 (Actos) 15, 30, 45 mg tablets

Rosiglitazone (Avandia) 2, 4, 8 mg tablets

Indications
As adjunct to diet and exercise for type II diabetes

MOA
Increase insulin sensitivity by affecting PPAR-γ (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

Intermediate
Blood concentration

Fast

Slow

0 2 4 6 8 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, ½ 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