Pioglitazone + Glimepiride

Oral
Type 2 diabetes mellitus

CrCl <22 mL/min: Should start w/ glimepiride 1 mg/day prior to initiating pioglitazone + glimepiride combination.

Should start w/ glimepiride 1 mg/day prior to initiating pioglitazone + glimepiride combination.

Should be taken with food. Take w/ 1st main meal of the day.

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.

Patients w/ prior history of active bladder cancer; anaemia, G6PD deficiency, symptomatic heart failure. Premenopausal/anovulatory females. May exacerbate CHF. Do not initiate in patient w/ active liver disease of ALT >2.5 times the upper limit of normal at baseline. Hepatic and renal impairment. Pregnancy and lactation.

Fracture, macular oedema, hypoglycaemia, wt gain, peripheral oedema, upper resp tract infection, headache, nausea, anaemia, diarrhoea, UTI, limb pain.
Potentially Fatal: CHF, severe hypoglycaemia, oedema, haemolytic anaemia, hepatic failure.

PO: C

Monitor for signs and symptoms of heart failure (e.g. excessive, rapid wt gain, oedema, dyspnoea) after initiation.

Glimepiride: Symptoms: Severe hypoglycaemia w/ coma, seizure, or neurological impairment. Management: Admin glucagon or IV glucose. Additional carbohydrate intake may be necessary as hypoglycaemia may recur after apparent clinical recovery.

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.

Alcohol may increase hypoglycaemic effect.

Description:
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 β-cells. It also reduces glucose output from the liver and increases insulin sensitivity at peripheral target sites.
Pharmacokinetics:
Absorption: Pioglitazone: Rapidly absorbed from the GI tract. Time to peak plasma concentrations: W/in 2 hr. Bioavailability: >80%. Glimepiride: Completely absorbed from the GI tract. Time to peak plasma concentrations: 2-3 hr.
Distribution: Pioglitazone: Plasma protein binding: >99%. Glimepiride: Highly protein bound.
Metabolism: Pioglitazone: Extensively metabolised mainly by CYP2C8 isoenzyme to both active and inactive metabolites. Glimepiride: Extensively metabolised to hydroxy derivative by CYP2C9 isoenzyme and to carboxy derivative by cytosolic enzymes.
Excretion: Pioglitazone: Via urine and faeces. Plasma half-life: Up to 7 hr. Half-life: Up to 24 hr (active metabolites). Glimepiride: Via urine (approx 60%) and faeces (40%). Half-life: Approx 9 hr (after multiple doses).

Store at 25°C.

Antidiabetic Agents

Anon. Pioglitazone and Glimepiride. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 30/06/2014.

Buckingham R (ed). Glimepiride. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/07/2014.

Buckingham R (ed). Pioglitazone. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/07/2014.

Duetact Tablet (Takeda Pharmaceuticals America, Inc). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 01/07/2014.

Wickersham RM. Pioglitazone/Glimepiride. Facts and Comparisons [online]. St. Louis, MO. Wolters Kluwer Clinical Drug Information, Inc. https://www.wolterskluwercdi.com/facts-comparisons-online/. Accessed 01/07/2014.