Anti- Diabetic Agents

Alpha-glucosidase Inhibitors	Biguanides (Including combination products) - e.g. Metformin
Glitazones - Thiazolidinediones	Meglitinides (e.g. Prandin)
Sulfonylureas	Glucagon
extenatide (Byetta ®)	pramlintide (Symlin ® )

Alpha-glucosidase Inhibitors

acarbose (Precose ®):

Alpha-cosidase inhibitor. Dosing (Adults): Start: 25mg orally three times daily with meals, gradually increase as tolerated to maintenance of 50-100mg orally three times daily.

Miglitol (Glycet ®):

Alpha-cosidase inhibitor. Dosing (Adults): Start: 25 mg orally three times daily with meals. Maintenance: 50-100mg three times daily.

Biguanides (Including combination products)

metformin (Glucophage ®):

Decreases hepatic glucose production, decreasing intestinal absorption of glucose and improves insulin sensitivity (increases peripheral glucose uptake and utilization).

Management of type 2 diabetes mellitus: Standard release tablet or oral solution: Dosing (Adults): Start: 500 mg twice daily (give with the morning and evening meals) or 850 mg once daily; increase dosage incrementally. (A lower recommended starting dose and gradual increased dosage is recommended to minimize gastrointestinal symptoms).
Adjustment: Incremental dosing recommendations are based on dosage form:
500 mg tablet: One tablet/day at weekly intervals.
850 mg tablet: One tablet/day every other week.
Oral solution: 500 mg twice daily every other week.
Note: Doses of up to 2000 mg/day may be given in divided doses twice daily. If a dose >2000 mg/day is required, it may be better tolerated in three divided doses.
Maximum recommended dose: 2550 mg/day.

Extended release tablet: Initial: 500 mg once daily (with the evening meal). Dosage may be increased by 500 mg weekly. Maximum dose: 2000 mg once daily. If glycemic control is not achieved at maximum dose, may divide dose to 1000 mg twice daily. If doses >2000 mg/day are needed, switch to regular release tablets and titrate to maximum dose of 2550 mg/day.

Renal dosing: Metformin is contraindicated in the presence of renal dysfunction defined as a serum creatinine >1.5 mg/dL in males, or >1.4 mg/dL in females and in patients with abnormal clearance.
Hepatic impairment: Avoid metformin.

Supplied: Tablet: 500 mg, 850 mg, 1000 mg. Extended release tablet: 500 mg, 750 mg, 1000 mg. Oral solution: 100 mg/ml (118 ml, 473 ml).

Avandamet® (Rosiglitazone + Metformin)

Management of type 2 diabetes mellitus: initial (previously receiving rosiglitazone 4 mg/day): Avandamet® 2/500mg po bid. (previously receiving rosiglitazone 8 mg/day): 4/500mg po bid. (previously receiving metformin 1000 mg/day): 2/500mg po bid. (previously receiving metformin 2000 mg/day): 2/1000mg po bid.
Titrate in increments of rosiglitazone 4 mg and/or metformin 500 mg po daily. Maximum: 8 mg/2000 mg daily.

Other: take with meals. When switching from metformin and rosiglitazone therapy given as separate tablets, starting dose of Avandamet is the dose of each drug previously taken. Dose titration should occur at 1 to 2 week intervals. If the dose of metformin is increased, dose titration should occur at 8 to 12 week intervals. If the dose of rosiglitazone is increased therapeutic response evaluation should be based on fasting plasma glucose values. Monitoring: renal function, baseline and at least annually.
[Supplied: 1 mg/500 mg, 2 mg/500 mg, 4 mg/500 mg] .

Glucovance (Glyburide + Metformin)

Management of type 2 diabetes mellitus:
Dosing (initial): 1.25 mg/250 mg once or twice daily with meals. Dosage increases should be made in increments of 1.25 mg/250 mg per day every two weeks up to the minimum effective dose necessary to achieve adequate control of blood glucose. Glucovance 5 mg/500 mg should not be used as initial therapy due to an increased risk of hypoglycemia. Maximum recommended daily dose: 20 mg glyburide/2000 mg metformin.
Administration: Glucovance should be given with meals and should be initiated at a low dose, with gradual dose escalation in order to avoid hypoglycemia (largely due to glyburide), to reduce GI side effects (largely due to metformin), and to permit determination of the minimum effective dose for adequate control of blood glucose for the individual patient.

Glucovance Use in Previously Treated Patients: Recommended starting dose: 2.5 mg/500 mg or 5 mg/500 mg twice daily with meals. In order to avoid hypoglycemia, the starting dose of Glucovance should not exceed the daily doses of glyburide or metformin already being taken. The daily dose should be titrated in increments of no more than 5 mg/500 mg up to the minimum effective dose to achieve adequate control of blood glucose or to a maximum dose of 20 mg/2000 mg per day.

[Supplied: 1.25 mg/250 mg, 2.5 mg/500 mg, 5 mg/500 mg tablet ]

Metaglip (Glipizide + Metformin)

Management of type 2 diabetes mellitus:
Dosing (initial): 2.5 mg/250 mg qd with a meal. For patients whose FPG is 280 to 320 mg/dl a starting dose of Metaglip 2.5 mg/500 mg twice daily should be considered. The efficacy of Metaglip in patients whose FPG exceeds 320 mg/dl has not been established. Dosage increases to achieve adequate glycemic control should be made in increments of one tablet per day every two weeks up to maximum of 10 mg/1000 mg or 10 mg/2000 mg per day given in divided doses. Maximum recommended daily dose: 20 mg glipizide/2000 mg metformin.

Second-Line Therapy For patients not adequately controlled on either glipizide (or another sulfonylurea) or metformin alone: 2.5 mg/500 mg or 5mg/500mg bid with the morning and evening meals. In order to avoid hypoglycemia, the starting dose of Metaglip should not exceed the daily doses of glipizide or metformin already being taken. The daily dose should be titrated in increments of no more than 5 mg/500 mg up to the minimum effective dose to achieve adequate control of blood glucose or to a maximum dose of 20 mg/2000 mg per day.

[Supplied: 2.5 mg/250 mg, 2.5 mg/500 mg, 5 mg/500 mg tablet ]

Glitazones - Thiazolidinediones

pioglitazone (Actos ®):

Acts primarily by decreasing insulin resistance.
Dosing (Adults): Start: 15-30 mg orally once daily. Maximum: 45 mg/day.

rosiglitazone (Avandia ®):

Monotherapy or combine with metformin.
Dosing (Adults): Start: 4 mg orally once daily or divided twice daily. Max 8 mg/day. Monitor LFT's every 2 months for first year.

Meglitinides

Nateglinide (Starlix ®)

Usual: 120 mg po tid (1-30 minutes before meals). Give alone or in combination with metformin. MOA: stimulates insulin release.

repaglinide (Prandin ®):

(Non-sulfonylurea insulin releasing oral hypoglycemic agent)
Dosing (Adults): Start: 0.5 - 2 mg orally three times daily before meals. Maintenance: 0.5 - 4 mg three to four times daily. Maximum: 16 mg/day.

Sulfonylureas

Chlorpropamide (Diabinese ®):

Adult (usual): initial, 250 mg orally daily (usually as a single dose with breakfast). Maintenance 100-500 mg orally daily. Maximum 750 mg a day.
Diabetes insipidus: 100-250 mg orally once daily, adjusted at 2-3 day intervals as needed.

glimepiride (Amaryl ®):

Sulfonylurea. Dosing (Adults): Start: 1-2 mg orally once daily. Usual: 1-4 mg/day. Maximum: 8 mg/day.

glyburide (Micronase ®, Diabeta ®):

Sulfonylurea. Start 1.25 to 5 mg orally once daily. Usual: 1.25 to 20 mg orally once daily or divided twice daily. Max: 20 mg/day.

glipizide (Glucotrol ®):

Sulfonylurea. Dosing (Adults): start 5 mg orally once daily. Usual: 10-20mg orally once daily. Max: 40mg/day. Glucotrol XL: start 5 mg orally once daily. Max: 20mg/day.

Tolazamide (Tolinase ®):

Adult (usual): initial: 100-250 mg orally once daily. maintenance (dose range): 100-1000 mg orally daily. Max 1000 mg daily. [Supplied 100 mg , 250 mg , 500 mg tablet]

Tolbutamide (Orinase ®):

Adult (usual): initial: 1-2 g orally once daily in the morning or in divided doses. Maintenance, usual range 0.25-3 g orally daily. Max: 3 g daily [Supplied 500 mg tablet]

Other

Glucagon:

Hypoglycemia: 1 mg IV/IM/SC. Onset 5-20min. May repeat in 20 minutes as needed. Note: If patient fails to respond to glucagon, I.V. dextrose must be given.

Beta-blocker overdose: Separate glucagon receptors stimulate adenylcyclase improving heart rate, blood pressure and conduction defects. Adults: 3 - 5 mg (up to 10 mg) IV push (over 1 minute) followed by an IV drip - usually 1 to 5 mg/hour. Note: bolus dose may be repeated in 10 minutes. Usually causes nausea and vomiting. May give Reglan IV, Compazine or Tigan.

Diagnostic aid: I.M., I.V.: 0.25-2 mg 10 minutes prior to procedure

Monitor blood glucose levels in hypoglycemic patients until they are asymptomatic; effective in treating hypoglycemia only if sufficient liver glycogen is present; since liver glycogen availability is necessary to treat hypoglycemic patients, glucagon has virtually no effects on patients in states of starvation, adrenal insufficiency, or chronic hypoglycemia.
(Recommended routes): IM, IV, or SC. Half-life: 8 to 18 minutes.

extenatide (Byetta ®):

Mechanism: Analog of the hormone incretin (glucagon-like peptide 1 or GLP-1) which increases insulin secretion, increases b-cell growth/replication, slows gastric emptying, and may decrease food intake. When added to sulfonylureas and/or metformin, it results in additional lowering of hbA1c by approximately 0.5% to 1%.

Dosing (Adjunctive therapy of type 2 diabetes): Initial: 5 mcg SQ bid within 60 min prior to a meal (morning and evening). After 1 month, may be increased to 10 mcg SQ twice daily (based on response).

Renal
Not recommended in patients CRCL < 30 ml/min.

Supplied: Injection: [prefilled pen]: 250 mcg/ml (1.2 ml) [provides 5 mcg/dose]. 2.4 ml - [provides 10 mcg/dose]

pramlintide (Symlin ® )

Indications: (1) Adjunctive treatment with mealtime insulin in type 1 diabetes mellitus (insulin dependent, IDDM) patients who have failed to achieve desired glucose control despite optimal insulin therapy. (2) Adjunctive treatment with mealtime insulin in type 2 diabetes mellitus (noninsulin dependent, NIDDM) patients who have failed to achieve desired glucose control despite optimal insulin therapy, with or without concurrent sulfonylurea and/or metformin.

Mechanism: Synthetic analog of human amylin cosecreted with insulin by pancreatic beta cells. Reduces postprandial glucose increases via the following mechanisms: 1) prolongation of gastric emptying time, 2) reduction of postprandial glucagon secretion, and 3) reduction of caloric intake through centrally-mediated appetite suppression.

Dosage: Adult (usual):
Type 1 diabetes mellitus (insulin dependent) Initial: 15 mcg SQ immediately prior to meals. Titrate in 15 mcg increments every 3 days (if no significant nausea occurs) to target dose of 30-60 mcg (consider discontinuation if intolerant of 30 mcg dose). Note: When initiating pramlintide, reduce current insulin dose (including rapidly and mixed-acting preparations) by 50% to avoid hypoglycemia.

Type 2 diabetes mellitus: Initial: 60 mcg SQ immediately prior to meals. After 3-7 days, increase to 120 mcg prior to meals if no significant nausea occurs (if nausea occurs at 120 mcg dose, reduce to 60 mcg).

If pramlintide is discontinued for any reason, restart therapy with same initial titration protocol.

Administration: Do not mix with other insulins. Administer SQ into abdominal or thigh areas at sites distinct from concomitant insulin injections (do not administer into arm due to variable absorption). Rotate injection sites frequently. For oral medications in which a rapid onset of action is desired, administer 1 hr before, or 2 hrs after pramlintide, if possible.

Supplied: Injection: Pramlintide acetate 0.6 mg/ml (5 ml).

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David F. McAuley, Pharm.D., R.Ph. GlobalRPh Inc.

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