Glimepiride + Pioglitazone

Indications

Glimepiride + Pioglitazone is used for: Type 2 DM

Adult Dose

Oral Type 2 diabetes mellitus Adult: 30 mg/2 mg, OR 30 mg/4 mg: Initially, 1 tab once daily then titrate gradually as needed. Elderly: Should start w/ glimepiride 1 mg/day prior to initiating pioglitazone + glimepiride combination. Hepatic Impairment 1 mg/day glimpiride PO prior to initiating glimepiride/pioglitazone; titrate conservatively to avoid hypoglycemia Baseline ALT <2.5 xULN: Use caution Baseline ALT >2.5 xULN: Do not initiate ALT >3 xULN or jaundice after initiating therapy: Discontinue

Child Dose

Renal Dose

Renal Impairment CrCl <22 mL/min: 1 mg/day glimepiride PO prior to initiating glimepiride/pioglitazone; titrate conservatively to avoid hypoglycemia Base dose titration on fasting glucose levels CrCl >22 mL/min: 30 mg/2 mg or 30 mg/4 mg PO qDay initially

Administration

Contra Indications

History of allergic reaction to sulfonamide derivative. Patient w/ established CHF (NYHA class III or IV). Not intended for treatment of type 1 DM or diabetic ketoacidosis.

Precautions

Pioglitazone, like other thiazolidinediones, can cause dose-related fluid retention when used alone or in combination with other antidiabetic medications and is most common when is used in combination with insulin. Fluid retention may lead to or exacerbate congestive heart failure. Patients should be observed for signs and symptoms of congestive heart failure. If congestive heart failure develops, it should be managed according to current standards of care and discontinuation or dose reduction of must be considered. Lactation: Not known if crosses into breast milk, discontinue drug or breastfeeding

Pregnancy-Lactation

Interactions

Increased plasma levels w/ CYP2C8 inhibitors (e.g. gemfibrozil) and CYP2C9 inhibitors (e.g. fluconazole). Decreased plasma levels w/ CYP2C8 inducers (e.g. rifampicin). Colesevelam may reduce the max plasma concentration and total exposure of glimepiride. Concominant use w/ oral miconazole may lead to severe hypoglycaemia.

Adverse Effects

Side effects of Glimepiride + Pioglitazone : >10% Peripheral edema (6-12%),Upper respiratory tract infection (12-15%),Weight gain (9-13%),Hypoglycemia (13-16%) 1-10% Anemia (<2%),Limb pain (4-5%),Urinary tract infection (6-7%),Headache (4-7%),Diarrhea (4-6%),Nausea (4-5%)

Mechanism of Action

Pioglitazone, a thiazolidinedione, reduces blood glucose by improving target cell response to insulin w/o increasing pancreatic insulin secretion and is dependent on the presence of insulin for activity. Glimepiride, a sulfonylurea, stimulates insulin release from the pancreatic beta-cells. It also reduces glucose output from the liver and increases insulin sensitivity at peripheral target sites.