Dosing and uses of Duetact (glimepiride-pioglitazone)
Adult dosage forms and strengths
pioglitazone/glimepiride
tablet
- 30mg/2mg
- 30mg/4mg
Type 2 Diabetes Mellitus
Indicated for management of type 2 diabetes mellitus as adjunct to diet and exercise
Indicated for type 2 diabetes mellitus in patients treated with combination of pioglitazone and a sulfonylurea, or patients not adequately controlled on a sulfonylurea alone, or who have initially responded to pioglitazone and require additional glycemic control Management of diabetes mellitus as adjunct to diet and exercise
30 mg/2 mg, OR 30 mg/4 mg PO qDay; not to exceed 45 mg/8 mg
Dosage modifications
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
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
Dosing Considerations
Systolic dysfunction (NYHA I/II): Initiate after patient has been safely titrated to 30 mg of pioglitazone monotherapy
For use in type 2 DM patients treated with combination of pioglitazone and a sulfonylurea, or patients not adequately controlled on a sulfonylurea alone, or patients who have initially responded to pioglitazone and require additional glycemic controL
Pediatric dosage forms and strengths
Safety and efficacy not established
Geriatric dosage forms and strengths
1 mg/day glimpiride (as monotherapy) PO prior to initiating glimepiride/pioglitazone; titrate conservatively to avoid hypoglycemia
Duetact (glimepiride-pioglitazone) adverse (side) effects
>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%)
Postmarketing Reports
Thrombocytopenia and thrombocytopenic purpura
Warnings
Black box warnings
Thiazolidinediones (eg, pioglitazone) can cause or exacerbate congestive heart failure in some patients
After initiation and dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive, rapid weight gain; dyspnea; and/or edema)
If these signs or symptoms develop, the heart failure should be managed according to the current standards of care
Discontinuation or dose reduction of thiazolidinedione must be considered
Thiazolidinediones not recommended with symptomatic heart failure; initiation in patients with established NYHA class III or IV heart failure is contraindicated
Contraindications
Hypersensitivity
Diabetic ketoacidosis with of without coma
Active liver disease, increased serum transaminase levels
Not recommended in heart failure NYHA III-IV patients
Cautions
Increased risk of cardiovascular mortality
Edema; thiazolidinediones, which are peroxisome proliferator-activated receptor (PPAR) gamma agonists, can cause dose-related fluid retention, particularly when used in combination with insulin
Hemolytic anemia may occur with glucose 6-phosphate dehydrogenase (G6PD) deficiency when treated with sulfonylurea agents
Fluid retention may occur and can exacerbate or lead to congestive heart failure; combination use with insulin and use in congestive heart failure NYHA Class I and II may increase risk; monitor patients for signs and symptoms
Hypoglycemia may be severe. when insulin or an insulin secretagogue is used with pioglitazone, a lower insulin dose or insulin secretagogue dose may be needed to reduce risk of hypoglycemia
Postmarketing reports for glimepiride include anaphylaxis, angioedema, and Stevens-Johnson syndrome; promptly discontinue glimepiride, assess for other causes, institute appropriate monitoring and treatment, and initiate alternative treatment for diabetes
Postmarketing reports of hepatic failure, sometimes fatal; causality cannot be excluded; if liver injury detected, promptly interrupt therapy and assess patient for probable cause, then treat cause if possible, to resolution or stabilization; do not restart therapy if liver injury confirmed and no alternate etiology can be found
Dose-related edema may occur
Increased incidence of bone fracture reported
Macular edema reported; recommend regular eye exams in all patients with diabetes according to current standards of care with prompt evaluation for acute visual changes
No clinical studies establishing conclusive evidence of macrovascular risk reduction with glimepiride/pioglitazone or any other antidiabetic drug exist
Increase in weight gain possibly related to pioglitazone effects on fluid retention and fat accumulation
Cancer risk
- Bladder cancer
- 5-year interim results of a 10-year cohort study suggest that pioglitazone use >12 months increases the relative risk of developing bladder cancer in any given year by 40%, an increase from ~7 cases in 10,000 to ~10 cases in 10,000
- Greatest risk was shown in patients with long-term use and the highest cumulative doses
- FDA recommendations include not prescribing pioglitazone for patients with active bladder cancer and cautious use in patients with a history of bladder cancer
- 7/22/2015: A prospective study found that during ~7 years' follow-up, the rate of incident bladder cancer was higher in patients who had ever used pioglitazone than nonusers (89.8 vs. 75.9 per 100,000 person-years), but the difference was not significant after adjustment for potential confounders [JAMA 2015 July 21;314(3):265-277]
- Prostate cancer
- 7/22/2015: Compared with nonuse, pioglitazone use was associated with increased risk for prostate cancer (453.3 vs. 449.3 per 100,000 person-years) [JAMA 2015 July 21;314(3):265-277]
- Pancreatic cancer
- 7/22/2015: Compared with nonuse, pioglitazone use was associated with increased risk for pancreatic cancer (81.1 vs. 48.4 per 100,000 person-years) [JAMA 2015 July 21;314(3):265-277]
See also individual monographs
- Pioglitazone
- Glimepiride
Pregnancy and lactation
Pregnancy category: C
Lactation: Not known if crosses into breast milk, discontinue drug or breastfeeding
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
