Antidiabetic Medications

dr. Boby Suryawan

Goal

To understand the use and side effects of anti-

diabetic medications and be able to educate
patients.
 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
Biguanides (cont)

Patient Info
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
DPP-4 (cont)

Patient Info
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

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- (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

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, 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