What is Actos (pioglitazone)?
Actos (pioglitazone) is in a class of anti-diabetic drugs called thiazolidinediones used to treat type 2 diabetes in adults. It is used along with a healthy diabetic diet, regular exercise, weight control, smoking reduction, and careful monitoring of blood glucose. Actos may be used alone or in combination with other drugs that also lower blood glucose.
Common side effects of Actos include:
- upper respiratory tract infection,
- headache,
- sinusitis,
- muscle aches,
- tooth disorders,
- low blood sugar (hypoglycemia),
- and sore throat.
Serious side effects of Actos include:
- anemia,
- liver injury (symptoms include nausea, vomiting, abdominal pain, fatigue, loss of appetite, dark urine),
- fluid retention (edema),
- fractures,
- bladder cancer,
- diabetic macular edema,
- and reduced red blood cells.
Drug interactions of Actos include gemfibrozil or other drugs that reduce the activity of liver enzymes that break down Actos and rifampin.
There are no adequate studies of Actos in pregnant women. Actos may be used in pregnancy if the physician feels the potential risks are justified. It is unknown if Actos is secreted in breast milk and its effects on nursing infants are unknown. Consult your doctor before breastfeeding.
What are the important side effects of Actos (pioglitazone)?
WARNING
- Actos and similar drugs can cause or worsen congestive heart failure in some patients.
- Patients should be monitored for signs and symptoms of heart failure at the beginning of treatment and after dose increases. For example:
- excessive, rapid weight gain,
- dyspnea,
- and/or edema.
- Actos is not recommended for patients with symptomatic heart failure and patients with established New York Heart Association (NYHA) Class III or IV heart failure should not use Actos.
Other side effects of Actos
The most common side effects of Actos alone or in combination with sulfonylureas, metformin, or insulin are:
- Upper respiratory tract infection
- Headache
- Sinusitis
- Muscle aches
- Tooth disorders
- Hypoglycemia (low blood sugar)
- Sore throat
Possible serious side effects of Actos include:
- Anemia
- Liver injury
- Edema
- Fractures
- Bladder cancer
- Diabetic macular edema
Dose-related fluid accumulation (edema) can occur especially when combined with insulin. Fluid accumulation can worsen or lead to heart failure. Actos should not be used in patients with heart disease classified by the New York Heart Association (NYHA) as Class III and IV heart failure or symptomatic heart failure.
Fluid accumulation also may lead to macular edema, resulting in reduced vision. Actos also can reduce red blood cells.
There have been post-marketing reports of liver failure while taking Actos.
Actos has been associated with liver injury. Periodic monitoring of liver-related side effects and liver tests should be conducted in patients taking Actos.
Symptoms of liver injury are:
- Nausea
- Vomiting
- Abdominal pain
- Fatigue
- Anorexia (loss of appetite)
- Dark urine
Actos should be stopped if patients have symptoms of liver injury and liver function test results that are greater than three times the normal level. Liver blood tests are obtained before starting treatment. Monitoring liver tests during treatment is not recommended for patients without liver disease.
Actos may cause ovulation in women who have stopped ovulating if they are premenopausal and insulin resistant. This may lead to pregnancy. For women (but not men) taking Actos, there is an increased risk of bone fractures of the distal bones of the arm and leg. Patients taking Actos should maintain proper bone health.
Actos (pioglitazone) side effects list for healthcare professionals
The following serious adverse reactions are discussed elsewhere in the labeling:
- Congestive heart failure
- Edema
- Fractures
Clinical Trials Experience
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- Over 8500 patients with type 2 diabetes have been treated with Actos in randomized, double-blind, controlled clinical trials, including 2605 patients with type 2 diabetes and macrovascular disease treated with Actos in the PROactive clinical trial.
- In these trials, over 6000 patients have been treated with Actos for six months or longer, over 4500 patients have been treated with Actos for one year or longer, and over 3000 patients have been treated with Actos for at least two years.
- In six pooled 16-to 26-week placebo-controlled monotherapy and 16-to 24-week add-on combination therapy trials, the incidence of withdrawals due to adverse events was 4.5% for patients treated with Actos and 5.8% for comparator-treated patients.
- The most common adverse events leading to withdrawal were related to inadequate glycemic control, although the incidence of these events was lower (1.5%) with Actos than with placebo (3.0%).
- In the PROactive trial, the incidence of withdrawals due to adverse events was 9.0% for patients treated with Actos and 7.7% for placebo-treated patients. Congestive heart failure was the most common serious adverse event leading to withdrawal occurring in 1.3% of patients treated with Actos and 0.6% of patients treated with placebo.
Common Adverse Events: 16-To 26-Week Monotherapy Trials
A summary of the incidence and type of common adverse events reported in three pooled 16to 26-week placebo-controlled monotherapy trials of Actos is provided in Table 1.
Terms that are reported represent those that occurred at an incidence of >5% and more commonly in patients treated with Actos than in patients who received placebo. None of these adverse events were related to Actos dose.
Table 1. Three Pooled 16-to 26-Week Placebo-Controlled Clinical Trials of Actos Monotherapy: Adverse Events Reported at an Incidence >5% and More Commonly in Patients Treated with Actos than in Patients Treated with Placebo
% of Patients | ||
Placebo N=259 | Actos N=606 | |
Upper Respiratory Tract Infection | 8.5 | 13.2 |
Headache | 6.9 | 9.1 |
Sinusitis | 4.6 | 6.3 |
Myalgia | 2.7 | 5.4 |
Pharyngitis | 0.8 | 5.1 |
Common Adverse Events: 16-To 24-Week Add-On Combination Therapy Trials
A summary of the overall incidence and types of common adverse events reported in trials of Actos add-on to sulfonylurea is provided in Table 2. Terms that are reported represent those that occurred at an incidence of >5% and more commonly with the highest tested dose of Actos.
Table 2. 16-to 24-Week Clinical Trials of Actos Add-on to Sulfonylurea
16-Week Placebo-Controlled Trial Adverse Events Reported in >5% of Patients and More Commonly in Patients Treated with Actos 30 mg + Sulfonylurea than in Patients Treated with Placebo + Sulfonylurea | |||
% of Patients | |||
Placebo + Sulfonylurea N=187 | Actos 15 mg + Sulfonylurea N=184 | Actos 30 mg + Sulfonylurea N=189 | |
Edema | 2.1 | 1.6 | 12.7 |
Headache | 3.7 | 4.3 | 5.3 |
Flatulence | 0.5 | 2.7 | 6.3 |
Weight Increased | 0 | 2.7 | 5.3 |
24-Week Non-Controlled Double-Blind Trial Adverse Events Reported in >5% of Patients and More Commonly in Patients Treated with Actos 45 mg + Sulfonylurea than in Patients Treated with Actos 30 mg + Sulfonylurea | |||
% of Patients | |||
Actos 30 mg + Sulfonylurea N=351 | Actos 45 mg + Sulfonylurea N=351 | ||
Hypoglycemia | 13.4 | 15.7 | |
Edema | 10.5 | 23.1 | |
Upper Respiratory Tract Infection | 12.3 | 14.8 | |
Weight Increased | 9.1 | 13.4 | |
Urinary Tract Infection | 5.7 | 6.8 | |
Note: The preferred terms of edema peripheral, generalized edema, pitting edema and fluid retention were combined to form the aggregate term of “edema.” |
A summary of the overall incidence and types of common adverse events reported in trials of Actos add-on to metformin is provided in Table 3. Terms that are reported represent those that occurred at an incidence of >5% and more commonly with the highest tested dose of Actos.
Table 3. 16-to 24-Week Clinical Trials of Actos Add-on to Metformin
16-Week Placebo-Controlled Trial Adverse Events Reported in >5% of Patients and More Commonly in Patients Treated with Actos + Metformin than in Patients Treated with Placebo + Metformin | ||
% of Patients | ||
Placebo + Metformin N=160 | Actos 30 mg + Metformin N=168 | |
Edema | 2.5 | 6.0 |
Headache | 1.9 | 6.0 |
24-Week Non-Controlled Double-Blind Trial Adverse Events Reported in >5% of Patients and More Commonly in Patients Treated with Actos 45 mg + Metformin than in Patients Treated with Actos 30 mg + Metformin | ||
% of Patients | ||
Actos 30 mg + Metformin N=411 | Actos 45 mg + Metformin N=416 | |
Upper Respiratory Tract Infection | 12.4 | 13.5 |
Edema | 5.8 | 13.9 |
Headache | 5.4 | 5.8 |
Weight Increased | 2.9 | 6.7 |
Note: The preferred terms of edema peripheral, generalized edema, pitting edema and fluid retention were combined to form the aggregate term of “edema.” |
Table 4 summarizes the incidence and types of common adverse events reported in trials of Actos add-on to insulin. Terms that are reported represent those that occurred at an incidence of >5% and more commonly with the highest tested dose of Actos.
Table 4. 16-to 24-Week Clinical Trials of Actos Add-on to Insulin
16-Week Placebo-Controlled Trial Adverse Events Reported in >5% of Patients and More Commonly in Patients Treated with Actos 30 mg + Insulin than in Patients Treated with Placebo + Insulin | |||
% of Patients | |||
Placebo + Insulin N=187 | Actos 15 mg + Insulin N=191 | Actos 30 mg + Insulin N=188 | |
Hypoglycemia | 4.8 | 7.9 | 15.4 |
Edema | 7.0 | 12.6 | 17.6 |
Upper Respiratory Tract Infection | 9.6 | 8.4 | 14.9 |
Headache | 3.2 | 3.1 | 6.9 |
Weight Increased | 0.5 | 5.2 | 6.4 |
Back Pain | 4.3 | 2.1 | 5.3 |
Dizziness | 3.7 | 2.6 | 5.3 |
Flatulence | 1.6 | 3.7 | 5.3 |
24-Week Non-Controlled Double-Blind Trial Adverse Events Reported in >5% of Patients and More Commonly in Patients Treated with Actos 45 mg + Insulin than in Patients Treated with Actos 30 mg + Insulin | |||
% of Patients | |||
Actos 30 mg + Insulin N=345 | Actos 45 mg + Insulin N=345 | ||
Hypoglycemia | 43.5 | 47.8 | |
Edema | 22.0 | 26.1 | |
Weight Increased | 7.2 | 13.9 | |
Urinary Tract Infection | 4.9 | 8.7 | |
Diarrhea | 5.5 | 5.8 | |
Back Pain | 3.8 | 6.4 | |
Blood Creatine Phosphokinase Increased | 4.6 | 5.5 | |
Sinusitis | 4.6 | 5.5 | |
Hypertension | 4.1 | 5.5 | |
Note: The preferred terms of edema peripheral, generalized edema, pitting edema and fluid retention were combined to form the aggregate term of “edema.” |
A summary of the overall incidence and types of common adverse events reported in the PROactive trial is provided in Table 5. Terms that are reported represent those that occurred at an incidence of >5% and more commonly in patients treated with Actos than in patients who received placebo.
Table 5. PROactive Trial: Incidence and Types of Adverse Events Reported in >5% of Patients Treated with Actos and More Commonly than Placebo
% of Patients | ||
Placebo N=2633 | Actos N=2605 | |
Hypoglycemia | 18.8 | 27.3 |
Edema | 15.3 | 26.7 |
Cardiac Failure | 6.1 | 8.1 |
Pain in Extremity | 5.7 | 6.4 |
Back Pain | 5.1 | 5.5 |
Chest Pain | 5.0 | 5.1 |
Mean duration of patient follow-up was 34.5 months. |
Congestive Heart Failure
A summary of the incidence of adverse events related to congestive heart failure is provided in Table 6 for the 16-to 24-week add-on to sulfonylurea trials, for the 16-to 24-week add-on to insulin trials, and for the 16-to 24-week add-on to metformin trials. None of the events were fatal.
Table 6. Treatment-Emergent Adverse Events of Congestive Heart Failure (CHF)
Patients Treated with Actos or Placebo Added on to a Sulfonylurea | |||||
Number (%) of Patients | |||||
Placebo-Controlled Trial (16 weeks) | Non-Controlled Double-Blind Trial (24 weeks) | ||||
Placebo + Sulfonylurea N=187 | Actos 15 mg + Sulfonylurea N=184 | Actos 30 mg + Sulfonylurea N=189 | Actos 30 mg + Sulfonylurea N=351 | Actos 45 mg + Sulfonylurea N=351 | |
At least one congestive heart failure event | 2 (1.1%) | 0 | 0 | 1 (0.3%) | 6 (1.7%) |
Hospitalized | 2 (1.1%) | 0 | 0 | 0 | 2 (0.6%) |
Patients Treated with Actos or Placebo Added on to Insulin | |||||
Number (%) of Patients | |||||
Placebo-Controlled Trial (16 weeks) | Non-Controlled Double-Blind Trial (24 weeks) | ||||
Placebo + Insulin N=187 | Actos 15 mg + Insulin N=191 | Actos 30 mg + Insulin N=188 | Actos 30 mg + Insulin N=345 | Actos 45 mg + Insulin N=345 | |
At least one congestive heart failure event | 0 | 2 (1.0%) | 2 (1.1%) | 3 (0.9%) | 5 (1.4%) |
Hospitalized | 0 | 2 (1.0%) | 1 (0.5%) | 1 (0.3%) | 3 (0.9%) |
Patients Treated with Actos or Placebo Added on to Metformin | |||||
Number (%) of Patients | |||||
Placebo-Controlled Trial (16 weeks) | Non-Controlled Double-Blind Trial (24 weeks) | ||||
Placebo + Metformin N=160 | Actos 30 mg + Metformin N=168 | Actos 30 mg + Metformin N=411 | Actos 45 mg + Metformin N=416 | ||
At least one congestive heart failure event | 0 | 1 (0.6%) | 0 | 1 (0.2%) | |
Hospitalized | 0 | 1 (0.6%) | 0 | 1 (0.2%) |
Patients with type 2 diabetes and NYHA class II or early class III congestive heart failure were randomized to receive 24 weeks of double-blind treatment with either Actos at daily doses of 30 mg to 45 mg (n=262) or glyburide at daily doses of 10 mg to 15 mg (n=256). A summary of the incidence of adverse events related to congestive heart failure reported in this study is provided in Table 7.
Table 7. Treatment-Emergent Adverse Events of Congestive Heart Failure (CHF) in Patients with NYHA Class II or III Congestive Heart Failure Treated with Actos or Glyburide
Number (%) of Subjects | ||
Actos N=262 | Glyburide N=256 | |
Death due to cardiovascular causes (adjudicated) | 5 (1.9%) | 6 (2.3%) |
Overnight hospitalization for worsening CHF (adjudicated) | 26 (9.9%) | 12 (4.7%) |
Emergency room visit for CHF (adjudicated) | 4 (1.5%) | 3 (1.2%) |
Patients experiencing CHF progression during study | 35 (13.4%) | 21 (8.2%) |
Congestive heart failure events leading to hospitalization that occurred during the PROactive trial are summarized in Table 8.
Table 8. Treatment-Emergent Adverse Events of Congestive Heart Failure (CHF) in PROactive Trial
Number (%) of Patients | ||
Placebo N=2633 | Actos N=2605 | |
At least one hospitalized congestive heart failure event | 108 (4.1%) | 149 (5.7%) |
Fatal | 22 (0.8%) | 25 (1.0%) |
Hospitalized, nonfatal | 86 (3.3%) | 124 (4.7%) |
Cardiovascular Safety
- In the PROactive trial, 5238 patients with type 2 diabetes and a history of macrovascular disease were randomized to Actos (N=2605), force-titrated up to 45 mg daily or placebo (N=2633) in addition to standard of care.
- Almost all patients (95%) were receiving cardiovascular medications (beta blockers, ACE inhibitors, angiotensin II receptor blockers, calcium channel blockers, nitrates, diuretics, aspirin, statins and fibrates).
- At baseline, patients had a mean age of 62 years, mean duration of diabetes of 9.5 years, and mean HbA1c of 8.1%.
- Mean duration of follow-up was 34.5 months.
- The primary objective of this trial was to examine the effect of Actos on mortality and macrovascular morbidity in patients with type 2 diabetes mellitus who were at high risk for macrovascular events.
- The primary efficacy variable was the time to the first occurrence of any event in a cardiovascular composite endpoint that included all-cause mortality, nonfatal myocardial infarction (MI) including silent MI, stroke, acute coronary syndrome, cardiac intervention including coronary artery bypass grafting or percutaneous intervention, major leg amputation above the ankle, and bypass surgery or revascularization in the leg.
- A total of 514 (19.7%) patients treated with Actos and 572 (21.7%) placebo-treated patients experienced at least one event from the primary composite endpoint (hazard ratio 0.90; 95% Confidence Interval: 0.80, 1.02; p=0.10).
- Although there was no statistically significant difference between Actos and placebo for the three-year incidence of a first event within this composite, there was no increase in mortality or in total macrovascular events with Actos.
- The number of first occurrences and total individual events contributing to the primary composite endpoint is shown in Table 9.
Table 9. PROactive: Number of First and Total Events for Each Component within the Cardiovascular Composite Endpoint
Cardiovascular Events | Placebo N=2633 | Actos N=2605 | ||
First Events n (%) | Total events n | First Events n (%) | Total events n | |
Any event | 572 (21.7) | 900 | 514 (19.7) | 803 |
All-cause mortality | 122 (4.6) | 186 | 110 (4.2) | 177 |
Nonfatal myocardial infarction (MI) | 118 (4.5) | 157 | 105 (4.0) | 131 |
Stroke | 96 (3.6) | 119 | 76 (2.9) | 92 |
Acute coronary syndrome | 63 (2.4) | 78 | 42 (1.6) | 65 |
Cardiac intervention (CABG/PCI) | 101 (3.8) | 240 | 101 (3.9) | 195 |
Major leg amputation | 15 (0.6) | 28 | 9 (0.3) | 28 |
Leg revascularization | 57 (2.2) | 92 | 71 (2.7) | 115 |
CABG = coronary artery bypass grafting; PCI = percutaneous intervention |
Weight Gain
- Dose-related weight gain occurs when Actos is used alone or in combination with other antidiabetic medications.
- The mechanism of weight gain is unclear but probably involves a combination of fluid retention and fat accumulation.
- Tables 10 and 11 summarize the changes in body weight with Actos and placebo in the 16to 26-week randomized, double-blind monotherapy and 16-to 24-week combination add-on therapy trials and in the PROactive trial.
Table 10. Weight Changes (kg) from Baseline During Randomized, Double-Blind Clinical Trials
Control Group (Placebo) | Actos 15 mg | Actos 30 mg | Actos 45 mg | ||
Median (25th/75th percentile) | Median (25th/75th percentile) | Median (25th/75th percentile) | Median (25th/75th percentile) | ||
Monotherapy (16 to 26 weeks) | -1.4 (-2.7/0.0) N=256 | 0.9 (-0.5/3.4) N=79 | 1.0 (-0.9/3.4) N=188 | 2.6 (0.2/5.4) N=79 | |
Combination Therapy (16 to 24 weeks) | Sulfonylurea | -0.5 (-1.8/0.7) N=187 | 2.0 (0.2/3.2) N=183 | 3.1 (1.1/5.4) N=528 | 4.1 (1.8/7.3) N=333 |
Metformin | -1.4 (-3.2/0.3) N=160 | N/A | 0.9 (-1.3/3.2) N=567 | 1.8 (-0.9/5.0) N=407 | |
Insulin | 0.2 (-1.4/1.4) N=182 | 2.3 (0.5/4.3) N=190 | 3.3 (0.9/6.3) N=522 | 4.1 (1.4/6.8) N=338 |
Table 11. Median Change in Body Weight in Patients Treated with Actos Versus Patients Treated with Placebo During the Double-Blind Treatment Period in the PROactive Trial
Placebo | Actos | |
Median (25th/75th percentile) | Median (25th/75th percentile) | |
Change from baseline to final visit (kg) | -0.5 (-3.3, 2.0) N=2581 | +3.6 (0.0, 7.5) N=2560 |
Note: Median exposure for both Actos and Placebo was 2.7 years. |
Edema
- Edema induced from taking Actos is reversible when Actos is discontinued. The edema usually does not require hospitalization unless there is coexisting congestive heart failure.
- A summary of the frequency and types of edema adverse events occurring in clinical investigations of Actos is provided in Table 12.
Table 12. Adverse Events of Edema in Patients Treated with Actos
Number (%) of Patients | |||||
Placebo | Actos 15 mg | Actos 30 mg | Actos 45 mg | ||
Monotherapy (16 to 26 weeks) | 3 (1.2%) N=259 | 2 (2.5%) N= 81 | 13 (4.7%) N= 275 | 11 (6.5%) N=169 | |
Combined Therapy (16 to 24 weeks) | Sulfonylurea | 4 (2.1%) N=187 | 3 (1.6%) N=184 | 61 (11.3%) N=540 | 81 (23.1%) N=351 |
Metformin | 4 (2.5%) N=160 | N/A | 34 (5.9%) N=579 | 58 (13.9%) N=416 | |
Insulin | 13 (7.0%) N=187 | 24 (12.6%) N=191 | 109 (20.5%) N=533 | 90 (26.1%) N=345 | |
Note: The preferred terms of edema peripheral, generalized edema, pitting edema and fluid retention were combined to form the aggregate term of “edema.” |
Table 13. Adverse Events of Edema in Patients in the PROactive Trial
Number (%) of Patients | |
Placebo N=2633 | Actos N=2605 |
419 (15.9%) | 712 (27.3%) |
Note: The preferred terms of edema peripheral, generalized edema, pitting edema and fluid retention were combined to form the aggregate term of “edema.” |
Hepatic Effects
- There has been no evidence of induced hepatotoxicity with Actos in the Actos controlled clinical trial database to date.
- One randomized, double-blind 3-year trial comparing Actos to glyburide as add-on to metformin and insulin therapy was specifically designed to evaluate the incidence of serum ALT elevation to greater than three times the upper limit of the reference range, measured every eight weeks for the first 48 weeks of the trial then every 12 weeks thereafter.
- A total of 3/1051 (0.3%) patients treated with Actos and 9/1046 (0.9%) patients treated with glyburide developed ALT values greater than three times the upper limit of the reference range.
- None of the patients treated with Actos in the Actos controlled clinical trial database to date have had a serum ALT greater than three times the upper limit of the reference range and a corresponding total bilirubin greater than two times the upper limit of the reference range, a combination predictive of the potential for severe drug-induced liver injury.
Hypoglycemia
- In the Actos clinical trials, adverse events of hypoglycemia were reported based on clinical judgment of the investigators and did not require confirmation with fingerstick glucose testing.
- In the 16-week add-on to sulfonylurea trial, the incidence of reported hypoglycemia was 3.7% with Actos 30 mg and 0.5% with placebo.
- In the 16-week add-on to insulin trial, the incidence of reported hypoglycemia was:
- 7.9% with Actos 15 mg,
- 15.4% with Actos 30 mg,
- and 4.8% with placebo.
- The incidence of reported hypoglycemia was higher with Actos 45 mg compared to Actos 30 mg in both the 24-week add-on to sulfonylurea trial (15.7% vs. 13.4%) and in the 24-week add-on to insulin trial (47.8% vs. 43.5%).
- Three patients in these four trials were hospitalized due to hypoglycemia. All three patients were receiving Actos 30 mg (0.9%) in the 24-week add-on to insulin trial.
- An additional 14 patients reported severe hypoglycemia (defined as causing considerable interference with patient’s usual activities) that did not require hospitalization.
- These patients were receiving Actos 45 mg in combination with sulfonylurea (n=2) or Actos 30 mg or 45 mg in combination with insulin (n=12).
Urinary Bladder Tumors
- Tumors were observed in the urinary bladder of male rats in the two-year carcinogenicity study.
- During the three year PROactive clinical trial, 14 patients out of 2605 (0.54%) randomized to Actos and 5 out of 2633 (0.19%) randomized to placebo were diagnosed with bladder cancer.
- After excluding patients in whom exposure to study drug was less than one year at the time of diagnosis of bladder cancer, there were 6 (0.23%) cases on Actos and two (0.08%) cases on placebo.
- After completion of the trial, a large subset of patients was observed for up to 10 additional years, with little additional exposure to Actos.
- During the 13 years of both PROactive and observational follow-up, the occurrence of bladder cancer did not differ between patients randomized to Actos or placebo (HR =1.00; 95% CI: 0.59-1.72).
Laboratory Abnormalities
Hematologic Effects
- Actos may cause decreases in hemoglobin and hematocrit.
- In placebo-controlled monotherapy trials, mean hemoglobin values declined by 2% to 4% in patients treated with Actos compared with a mean change in hemoglobin of -1% to +1% in placebo-treated patients.
- These changes primarily occurred within the first 4 to 12 weeks of therapy and remained relatively constant thereafter.
- These changes may be related to increased plasma volume associated with Actos therapy and are not likely to be associated with any clinically significant hematologic effects.
Creatine Phosphokinase
- During protocol-specified measurement of serum creatine phosphokinase (CPK) in Actos clinical trials, an isolated elevation in CPK to greater than 10 times the upper limit of the reference range was noted in nine (0.2%) patients treated with Actos (values of 2150 to 11400 IU/L) and in no comparator-treated patients.
- Six of these nine patients continued to receive Actos, two patients were noted to have the CPK elevation on the last day of dosing and one patient discontinued Actos due to the elevation.
- These elevations resolved without any apparent clinical sequelae.
- The relationship of these events to Actos therapy is unknown.
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of Actos.
Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- New onset or worsening diabetic macular edema with decreased visual acuity.
- Fatal and nonfatal hepatic failure.
Postmarketing reports of congestive heart failure have been reported in patients treated with Actos, both with and without previously known heart disease and both with and without concomitant insulin administration.
In postmarketing experience, there have been reports of unusually rapid increases in weight and increases in excess of that generally observed in clinical trials. Patients who experience such increases should be assessed for fluid accumulation and volume-related events such as excessive edema and congestive heart failure.
What drugs interact with Actos (pioglitazone)?
Strong CYP2C8 Inhibitors
An inhibitor of CYP2C8 (e.g., gemfibrozil) significantly increases the exposure (area under the serum concentration-time curve or AUC) and half-life (t½) of pioglitazone. Therefore, the maximum recommended dose of Actos is 15 mg daily if used in combination with gemfibrozil or other strong CYP2C8 inhibitors.
CYP2C8 Inducers
An inducer of CYP2C8 (e.g., rifampin) may significantly decrease the exposure (AUC) of pioglitazone. Therefore, if an inducer of CYP2C8 is started or stopped during treatment with Actos, changes in diabetes treatment may be needed based on clinical response without exceeding the maximum recommended daily dose of 45 mg for Actos.
Topiramate
A decrease in the exposure of pioglitazone and its active metabolites were noted with concomitant administration of pioglitazone and topiramate. The clinical relevance of this decrease is unknown; however, when Actos and topiramate are used concomitantly, monitor patients for adequate glycemic control.
Summary
Actos (pioglitazone) is in a class of anti-diabetic drugs called thiazolidinediones used to treat type 2 diabetes in adults. It is used along with a healthy diabetic diet, regular exercise, weight control, smoking reduction, and careful monitoring of blood glucose. Actos may be used alone or in combination with other drugs that also lower blood glucose. Common side effects of Actos include upper respiratory tract infection, headache, sinusitis, muscle aches, tooth disorders, low blood sugar (hypoglycemia), and sore throat. Drug interactions of Actos include gemfibrozil or other drugs that reduce the activity of liver enzymes that break down Actos and rifampin. There are no adequate studies of Actos in pregnant women. Actos may be used in pregnancy if the physician feels the potential risks are justified. It is unknown if Actos is secreted in breast milk and its effects on nursing infants are unknown. Consult your doctor before breastfeeding.
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Discover the best and worst meals for diabetes-savvy dining. See how to avoid carbs and control your blood sugar with healthier...
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Type 2 Diabetes: Test Your Medical IQ
What causes type 2 diabetes? Can it be prevented? Take this online quiz and challenge your knowledge of this common condition....
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Type 1 Diabetes Quiz: Test Your Medical IQ
What are the causes of type 1 diabetes? Take this quiz and challenge your knowledge of causes, symptoms, diagnosis and treatments...
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Diabetes Quiz: Test Your Medical IQ
Take the Diabetes Quiz and learn the causes, signs, symptoms, and types of this growing epidemic. What does diabetes have to do...
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Diabetes Travel: Tips for Better Diabetes Control
Diabetes shouldn't stop you from traveling! Learn tips for packing diabetic supplies, controlling blood sugar while changing time...
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Diabetes Diet: 11 Low-Sugar Drink Ideas
Searching for low-sugar drink ideas? This pictures slideshow has eleven beverages ideal for people with diabetes and those...
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Diabetes: 15 Famous Celebrities With Diabetes
See pictures of celebrities that have been diagnosed with type 1 or type 2 diabetes including Mary Tyler Moore, Salma Hayek, and...
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Slideshow: Diabetes Management in 10 Minutes
Learn 10 simple ways to better manage your diabetes. See tips for controlling blood sugar, diet and exercise and other helpful...
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Diabetes: Guide to Diabetic Peripheral Neuropathy
Diabetes can damage the nerves that help you feel pain, heat, and cold, especially in your feet. Learn about the symptoms of...
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10 Muscle-Building Exercises for Diabetes
Watch this slideshow on Diabetes and Exercise. If you have diabetes, see how strengthening your muscles with these 10 weight...
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Diabetes: Diabetic Peripheral Neuropathy Treatment
This nerve damage is a common complication of both type 1 and type 2 diabetes. Find out how to prevent it, slow its progression,...
Related Disease Conditions
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Normal Blood Sugar Levels In Adults with Diabetes
People with diabetes can manage and prevent low or high blood sugar levels (hyperglycemia or hypoglycemia) by keeping a log of your blood sugar levels when you are eating and fasting and eat foods that are high in carbohydrates and sugar, for example, buttered potatoes, candy, sugary desserts, and fatty foods. Blood tests, for example, the hemoglobin A1c test (A1c test) and urinalysis can diagnose the type of diabetes the person has. Diabetes during pregnancy, called gestational diabetes, should be managed by you and your OB/GYN or another healthcare professional. Extremely high levels of blood glucose in the blood can be dangerous and life threatening if you have type 1, type 2, or gestational diabetes. If you or someone that you are with has extremely high blood glucose levels, call 911 or go to your nearest Urgent Care or Emergency Department immediately. To prevent and manage high blood glucose levels in people with diabetes keep a log of your blood sugar levels, eat foods that are high in carbohydrates sugar, for example, buttered potatoes, candy, sugary deserts, and fatty foods that you can share with your doctor and other healthcare professionals.
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Diabetes (Type 1 and Type 2)
Diabetes is a chronic condition characterized by high levels of sugar (glucose) in the blood. The two types of diabetes are referred to as type 1 (insulin dependent) and type 2 (non-insulin dependent). Symptoms of diabetes include increased urine output, thirst, hunger, and fatigue. Treatment of diabetes depends on the type.
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Type 2 Diabetes Diet Plan
A type 2 diabetes diet or a type 2 diabetic diet is important for blood sugar (glucose) control in people with diabetes to prevent complications of diabetes. There are a variety of type 2 diabetes diet eating plans such as the Mediterranean diet, Paleo diet, ADA Diabetes Diet, and vegetarian diets.Learn about low and high glycemic index foods, what foods to eat, and what foods to avoid if you have type 2 diabetes.
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Pregnancy and Gestational Diabetes
Gestational diabetes is a form of diabetes that can occur during pregnancy. Pregnant women with gestational diabetes have not had the condition prior to becoming pregnant. Usually, gestational diabetes has no symptoms or signs and of gestational diabetes. Gestational diabetes can cause insulin resistance, hypoglycemia, hypoglycemia, and diabetic ketoacidosis. Treatment of gestational diabetes is managing the condition by checking your blood sugar as recommended, diet changes, getting enough exercise, and monitoring your baby's growth.
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Diabetes-Related Dental Problems
Second Source WebMD Medical Reference
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Type 2 Diabetes: Diagnosing Diabetes
Second Source WebMD Medical Reference
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Controlling Diabetes
Second Source WebMD Medical Reference
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Diabetes Symptoms in Women
Diabetes symptoms in women include vaginal itching, pain, or discharge, loss of interest or pain after having sex, polycystic ovarian syndrome (POS), and urinary tract infections or UTIs (which are more common in women. Symptoms of diabetes that are the same in women and men are excessive thirst and hunger, bad breath, and skin infections, darkening of skin in areas of body creases (acanthosis nigricans), breath odor that is fruity, sweet, or acetone, and tingling or numbness in the hands or feet, blurred vision, fatigue, tingling or numbness in the hands or feet, wounds that heal slowly, irritability, and weight loss or gain. Complications of type 1 and type 2 diabetes are the same, for example, skin, eye, and circulation problems, low blood sugar (hypoglycemia), high blood sugar (hyperglycemia), ketoacidosis, and amputation. If diabetes is not managed a person may not survive.
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Type 2 Diabetes
Type 2 diabetes is a chronic condition that may be reversible with diet and lifestyle changes. Symptoms include excessive thirst, frequent urination, weight loss, fatigue, and an unusual odor to your urine. Most people don't know they have type 2 diabetes until they have a routine blood test. Treatment options include medications, a type 2 diabetes diet, and other lifestyle changes.
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Diabetes Treatment: Medication, Diet, and Insulin
The major goal in treating diabetes is controlling elevated blood sugar without causing abnormally low levels of blood sugar. Type 1 diabetes is treated with: insulin, exercise, and a diabetic diet. Type 2 diabetes is first treated with: weight reduction, a diabetic diet, and exercise. When these measures fail to control the elevated blood sugar, oral medications are used. If oral medications are still insufficient, insulin medications are considered.
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Diabetes Symptoms in Men
Early symptoms of diabetes are different in men, such as low testosterone. In many cases, prediabetes that will progress to type 2 diabetes if it is not treated early.
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Prediabetes
Prediabetes is a situation where a person's blood sugar levels are higher than they should be, but aren't high enough to be diagnosed with type 2 diabetes. There are no signs or symptoms of prediabetes. Some of the risk factors for prediabetes are high blood pressure, high cholesterol, heart disease, smoking, family history, poor diet, and lack of activity. Diet changes along with other healthy lifestyle changes are important in treating prediabetes.
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Type 1 vs. Type 2 Diabetes: Differences
Diabetes mellitus is a metabolic condition in which a person's blood sugar (glucose) levels are too high. Over 29.1 million children and adults in the US have diabetes. Of that, 8.1 million people have diabetes and don't even know it. Type 1 diabetes (insulin-dependent, juvenile) is caused by a problem with insulin production by the pancreas. Type 2 diabetes (non-insulin dependent) is caused by: Eating a lot of foods and drinking beverages with simple carbohydrates (pizza, white breads, pastas, cereals, pastries, etc.) and simple sugars (donuts, candy, etc.) Consuming too many products with artificial sweeteners (We found out that they are bad for us!) Lack of activity Exercise Stress Genetics While the signs and symptoms of both types of diabetes are the same, which include: Increased urination Increased hunger Increased thirst Unexplained weight loss. However, the treatments are different. Type 1 diabetes is insulin dependent, which means a person with this type of diabetes requires treatment with insulin. People with type 2 diabetes require medication, lifestyle changes like eating a healthy diet, and getting regular exercise.
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Diabetes and Safe Medications for Colds & Flu
If you have diabetes and catch a cold or the flu, can be more difficult to recover from infections and their complications, for example, pneumonia. Home remedies and over-the-counter (OTC) drugs used for the treatment of the signs and symptoms of colds and the flu may affect blood sugar levels in people with diabetes.Some medications are OK to take if you have diabetes get a cold or the flu include nonsteroidal anti-inflammatory drugs or NSAIDs, like acetaminophen (Tylenol) and ibuprofen (Motrin) to control symptoms of fever and pain. Most cough syrups are safe to take; however, check with your pediatrician to see what medications are safe to give your child if he or she has type 1 or 2 diabetes. If you have diabetes and are sick with a cold or flu, you need to check your blood sugar levels more frequently. Continue taking your regular medications. Eat a diabetic low-glycemic index diet rich in antioxidants. To prevent colds and the flu drink at least eight 8 ounce glasses of water a day. To replenish fluids, drink sports drinks like Gatorade and Pedialyte to replenish electrolytes. Avoid people who are sick, sneezing, coughing, or have other symptoms of a cold or flu.
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Type 1 Diabetes (Symptoms, Causes, Diet, Treatment, Life Expectancy)
Type 1 diabetes mellitus (juvenile) is an auto-immune disease with no known cause at this time, although there are a few risk factors. Symptoms of type 1 diabetes include frequent urination, unintentional weight loss, dry and itchy skin, vision problems, wounds that heal slowly, and excessive thirst. Type 1 diabetes is diagnosed with blood tests. A healthy lifestyle and controlling blood glucose levels can improve life expectancy.
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Gestational Diabetes (Diabetes during Pregnancy))
Learning how to avoid gestational diabetes is possible and maintaining a healthy weight and diet before and during pregnancy can help. Discover risk factors, tests and treatments for, and signs and symptoms of gestational diabetes.
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How to Prevent Diabetes Naturally
Prediabetes is a condition in which a person has early symptoms of diabetes, but has not yet fully developed the condition. If prediabetes is not treated with lifestyle changes, the person could develop type 2 diabetes. Type 2 diabetes and prediabetes can be prevented with lifestyle changes, for example, eating a healthy diet, getting more exercise, reducing stress, quitting smoking, reducing or managing blood pressure and cholesterol, and managing any other health conditions or risk factors that you may have for developing type 2 diabetes.
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Diabetes Foot Problems
Diabetes related foot problems can affect your health with two problems: diabetic neuropathy, where diabetes affects the nerves, and peripheral vascular disease, where diabetes affects the flow of blood. Common foot problems for people with diabetes include athlete's foot, fungal infection of nails, calluses, corns, blisters, bunions, dry skin, foot ulcers, hammertoes, ingrown toenails, and plantar warts.
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Eye Problems and Diabetes
Diabetes and eye problems are generally caused by high blood sugar levels over an extended period of time. Types of eye problems in a person with diabetes include glaucoma, cataracts, and retinopathy. Examples of symptoms include blurred vision, headaches, eye aches, pain, halos around lights, loss of vision, watering eyes. Treatment for eye problems in people with diabetes depend on the type of eye problem. Prevention of eye problems include reducing blood pressure, cholesterol levels, quitting smoking, and maintaining proper blood glucose levels.
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Types of Diabetes Type 2 Medications
Type 2 diabetes oral medications are prescribed to treat type 2 diabetes in conjuction with lifestyle changes like diet and exercise. There are nine classes of drugs approved for the treatment of type 2 diabetes. Examples of type 2 oral diabetes medications include acarbose (Precose), chlorpropamide (Diabinese), glipizide (Glucotrol, Glucotrol XL), and metformin (Glucophage). Side effects, drug interactions, warnings and precautions, dosage, and breastfeeding and pregnancy safety information should be reviewed prior to taking any medication.
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Tips for Managing Type 1 and 2 Diabetes at Home
Managing your diabetes is a full time commitment. The goal of diabetic therapy is to control blood glucose levels and prevent the complications of diabetes. Information about exercise, diet, and medication will help you manage your diabetes better. Blood glucose reagent strips, blood glucose meters, urine glucose tests, tests for urinary ketones, continuous glucose sensors, and Hemoglobin A1C testing information will enable you to mange your diabetes at home successfully.
Treatment & Diagnosis
- Diabetes FAQs
- Type 2 Diabetes FAQs
- Type 1 Diabetes FAQs
- Diabetes - An Aspirin A Day
- Diabetes and Eye Disease...See No Evil
- Diabetes - David Meets Goliath
- Insulin...Getting Better All the Time
- Exercise Therapy in Type 2 Diabetes - Part 1
- Exercise Therapy in Diabetes - Part 2
- Insulin Resistance - Keypoints
- Diabetes Mellitus - The Work Pays Off
- Diabetes - Foot Care: A Walking Matter
- Ramipril, Heart Disease, Stroke & Diabetes
- Diabetes Type I...Insulin Therapy
- Heart Disease Stroke and Diabetes
- Hypoglycemia (Low Blood Sugar) Symptoms and Diabetes
- Rheumatoid Arthritis & Diabetes Gene (PTPN22)
- Diabetes Report From The National ADA Meeting 2003
- Diabetes Update - American Diabetes Association 2006
- What Foods to Eat to Reverse Diabetes
- How Bad Is Type 1 Diabetes?
- What Causes Type 1 Diabetes in Adults?
- Is Type 1 Diabetes Genetic?
- What Will Happen if Type 1 Diabetes Is Left Untreated?
- Can You Get Diabetes from Stress?
- How Do You Know if You Have Diabetes?
- Does Celiac Disease Cause Diabetes?
- Can oral diabetes medications cause impotence?
- Does Diabetes Cause Gum Disease?
- What Is the Treatment for Diabetes Eye Damage?
- Does Anti-Retroviral Therapy for HIV Cause Diabetes?
- Can You Have Type 1 Diabetes Without Symptoms?
- 6 Frequently Asked Diabetes Question
- What Kind of Candy Can You Eat With Diabetes?
- Is Weight Loss Caused by Diabetes Dangerous?
- Can Diabetes Cause Muscle Pain?
- 11 Diabetes Diet Tips for the Holidays
- Diabetes Diet
- Top 10 Questions to Ask Your Doctor About Diabetes
- Prediabetes Symptoms and Diagnosis
- Diabetes: Eating Well with Type 2 Diabetes
- Diabetes: What Can I Eat?
Medications & Supplements

Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.