Glimepiride + Pioglitazone

Glimepiride + Pioglitazone is used for: Type 2 DM

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

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

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.

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 Limited data in pregnant women are not sufficient to determine a drug-associated risk for major birth defects or miscarriage; there are clinical considerations related to fetal and neonatal adverse reactions and drug discontinuation if glimepiride is used during pregnancy; there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, pre-eclampsia, spontaneous abortions, preterm delivery, still birth and delivery complications; poorly controlled diabetes increases fetal risk for major birth defects, still birth, and macrosomia related morbidity Neonates of women with gestational diabetes, who are treated with sulfonylureas during pregnancy, may be at increased risk for neonatal intensive care unit admission, and may develop respiratory distress, hypoglycemia, birth injury, and be large for gestational age; prolonged severe hypoglycemia, lasting 4-10 days, reported in neonates born to mothers receiving a sulfonylurea at time of delivery and has been reported with use of agents with a prolonged half-life; observe newborns for symptoms of hypoglycemia and respiratory distress and manage accordingly Due to reports of prolonged severe hypoglycemia in neonates born to mothers receiving a sulfonylurea at time of delivery, therapy should be discontinued at least two weeks before expected delivery Lactation There is no information regarding presence of pioglitazone or glimepiride in human milk, effects on breastfed infant, or on milk production; pioglitazone and glimepiride are present in rat milk; however, due to species-specific differences in lactation physiology, animal data may not reliably predict drug levels in human milk The developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or from underlying maternal condition

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.

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%)

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.