• Piodiab indications
• Uses of Piodiab in details
• Piodiab description
• Piodiab dosage
• Piodiab interactions
• Piodiab side effects
• Piodiab contraindications

What is Piodiab?

Piodiab is an oral diabetes medicine that helps control blood sugar levels.

Piodiab is for people with type 2 diabetes. Piodiab is sometimes used in combination with insulin or other medications, but it is not for treating type 1 diabetes.

Piodiab may also be used for purposes not listed in this medication guide.

Piodiab indications

Monotherapy and Combination Therapy

Piodiab is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus in multiple clinical settings.

Important Limitations of Use

Piodiab exerts its antihyperglycemic effect only in the presence of endogenous insulin. Piodiab should not be used to treat type 1 diabetes or diabetic ketoacidosis, as it would not be effective in these settings.

Use caution in patients with liver disease.

How should I use Piodiab?

Use Piodiab as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Piodiab comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Piodiab refilled.
• Take Piodiab by mouth with or without food.
• Continue to take Piodiab even if you feel well. Do not miss any doses.
• Taking Piodiab at the same time each day will help you remember to take it.
• If you miss a dose of Piodiab, skip the missed dose and go back to your regular dosing schedule, unless your doctor directs you otherwise. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Piodiab.

Uses of Piodiab in details

Piodiab is an anti-diabetic drug (thiazolidinedione-type, also called "glitazones") used along with a proper diet and exercise program to control high blood sugar in patients with type 2 diabetes. It works by helping to restore your body's proper response to insulin, thereby lowering your blood sugar.

Controlling high blood sugar helps prevent kidney damage, blindness, nerve problems, loss of limbs, and sexual function problems. Proper control of diabetes may also lessen your risk of a heart attack or stroke.

Piodiab is used either alone or in combination with other anti-diabetic medications (such as metformin or a sulfonylurea such as glyburide).

Talk to your doctor about the risks and benefits of Piodiab.

How to use Piodiab

Read the Medication Guide provided by your pharmacist before you start using Piodiab and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth with or without food as directed by your doctor, usually once daily. Dosage is based on your medical condition, response to treatment, and if you are taking other anti-diabetic drugs. Your doctor will adjust your dose based on your blood sugar levels to find the best dose for you. Follow your doctor's directions carefully.

Take this medication regularly in order to get the most benefit from it. Remember to use it at the same time each day.

If you are already taking another anti-diabetic drug (such as metformin or a sulfonylurea), follow your doctor's directions carefully for stopping/continuing the old drug and starting this medication. Carefully follow the medication treatment plan, meal plan, and exercise program your doctor has recommended.

Check your blood sugar regularly as directed by your doctor. Keep track of the results, and share them with your doctor. Tell your doctor if your blood sugar measurements are too high or too low. Your dosage/treatment may need to be changed. It may take up to 2 to 3 months before the full benefit of this drug takes effect.

Piodiab description

Piodiab has been specially formulated with 20 nutrients to help safeguard the daily requirements with particular emphasis on those of special relevance to diabetics. These include vitamins B1, B6 and C, which are important factors in glucose metabolism.

Piodiab contains magnesium to help replace that which can be lose through excess excretion and zinc which plays an important role in insulin metabolism and action.

Nutritional Information of Piodiab: See table.

It does not contain gluten, starch, sugar, fat, salt, yeast, artificial colors and preservatives.

Piodiab is a 100% vitamin and mineral supplement capsule.

Piodiab dosage

Piodiab Dosage

Generic name: Piodiab HYDROCHLORIDE 15mg

Dosage form: tablet

The information at Drugs.com is not a substitute for medical advice. Always consult your doctor or pharmacist.

Recommendations for All Patients

Piodiab should be taken once daily and can be taken without regard to meals.

The recommended starting dose for patients without congestive heart failure is 15 mg or 30 mg once daily.

The recommended starting dose for patients with congestive heart failure (NYHA Class I or II) is 15 mg once daily.

The dose can be titrated in increments of 15 mg up to a maximum of 45 mg once daily based on glycemic response as determined by HbA1c.

After initiation of Piodiab or with dose increase, monitor patients carefully for adverse reactions related to fluid retention such as weight gain, edema, and signs and symptoms of congestive heart failure.

Liver tests (serum alanine and aspartate aminotransferases, alkaline phosphatase, and total bilirubin) should be obtained prior to initiating Piodiab. Routine periodic monitoring of liver tests during treatment with Piodiab is not recommended in patients without liver disease. Patients who have liver test abnormalities prior to initiation of Piodiab or who are found to have abnormal liver tests while taking Piodiab should be managed as described under Warnings and Precautions.

Concomitant Use with an Insulin Secretagogue or Insulin

If hypoglycemia occurs in a patient co-administered Piodiab and an insulin secretagogue (e.g., sulfonylurea), the dose of the insulin secretagogue should be reduced.

If hypoglycemia occurs in a patient co-administered Piodiab and insulin, the dose of insulin should be decreased by 10% to 25%. Further adjustments to the insulin dose should be individualized based on glycemic response.

Concomitant Use with Strong CYP2C8 Inhibitors

Coadministration of Piodiab and gemfibrozil, a strong CYP2C8 inhibitor, increases Piodiab exposure approximately 3-fold. Therefore, the maximum recommended dose of Piodiab is 15 mg daily when used in combination with gemfibrozil or other strong CYP2C8 inhibitors.

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Piodiab interactions

See also:
What other drugs will affect Piodiab?

Oral Contraceptives:

Co-administration of Piodiab (45 mg once daily) and an oral contraceptive (norethindrone 1 mg plus ethinyl estradiol 0.035 mg once daily) resulted in 11% and 11-14% decrease in ethinyl estradiol AUC and C_max, respectively. Clinical significance of a high variability on ethinyl estradiol pharmacokinetics is unknown.

Insulin or Insulin Secretagogues: The dose of insulin and insulin secretagogues (eg, sulfonylurea) should be reduced since concomitant administration may result in hypoglycemia.

Midazolam: Administration of Piodiab for 15 days followed by a 7.5 mg single dose of midazolam syrup resulted in a 26% reduction in midazolam C_max and AUC.

Strong CYP2C8 Inhibitors: Gemfibrozil (an inhibitor of CYP450 2C8) resulted in a 3-fold increase in the plasma concentration of parent Piodiab and also inhibited the further metabolism of M-III and M-IV. Careful blood glucose monitoring and dosage adjustments are suggested during co-administration of Piodiab and gemfibrozil. If used in combination with gemfibrozil or other strong CYP2C8 inhibitors, a maximum dose of Piodiab 15 mg should be used.

CYP2C8 Inducers: Co-administration of Piodiab with rifampicin (an inducer of CYP450 2C8) resulted in a 54% reduction in Piodiab's AUC. The dose of Piodiab may need to be increased when rifampicin is co-administered and glycemic control closely monitored.

If an inducer of CYP2C8 is started or stopped during treatment with Piodiab, the maximum recommended dose of 45 mg should not be exceeded and changes in diabetes treatment may be needed based on the patient's clinical response.

Drugs Metabolized via Cytochrome P-450: The cytochrome P-450 isoform, CYP3A4, is partially responsible for the metabolism of Piodiab. Potential pharmacokinetic interaction (reduction in C_max and AUC) with CYP3A4 substrates (eg, atorvastatin, nifedipine). Clinical significance of this finding is unknown.

Peak plasma concentration and area under the AUC of Piodiab may increase when taken concomitantly with CYP3A4 inhibitors eg, ketoconazole. However, pharmacokinetic interaction is unlikely with ranitidine which is a relatively weak CYP3A4 inhibitor.

In vitro studies have shown no inhibition of any subtype of cytochrome P-450. Interactions with substances metabolized by these enzymes are unlikely: Ciclosporin, calcium channel blockers, and HMGCoA reductase inhibitors.

Co-administration of Piodiab with the following drugs did not show pharmacokinetic interactions: Metformin, glipizide, digoxin, phenprocoumon, fexofenadine, CYP2C9 substrates (eg, warfarin), CYP1A2 substrates (eg, theophylline).

Piodiab side effects

See also:
What are the possible side effects of Piodiab?

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 Piodiab in randomized, double-blind, controlled clinical trials, including 2605 patients with type 2 diabetes and macrovascular disease treated with Piodiab in the PROactive clinical trial. In these trials, over 6000 patients have been treated with Piodiab for six months or longer, over 4500 patients have been treated with Piodiab for one year or longer, and over 3000 patients have been treated with Piodiab 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 Piodiab 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 Piodiab than with placebo (3.0%).

In the PROactive trial, the incidence of withdrawals due to adverse events was 9.0% for patients treated with Piodiab 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 Piodiab 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 16-to 26-week placebo-controlled monotherapy trials of Piodiab 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 Piodiab than in patients who received placebo. None of these adverse events were related to Piodiab dose.

Table 1: Three Pooled 16-to 26-Week Placebo-Controlled Clinical Trials of Piodiab Monotherapy: Adverse Events Reported at an Incidence > 5% and More Commonly in Patients Treated with Piodiab than in Patients Treated with Placebo

	% of Patients
Placebo N=259	Piodiab 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 Piodiab 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 Piodiab.

Table 2: 16-to 24-Week Clinical Trials of Piodiab Add-on to Sulfonylurea

	16-Week Placebo-Controlled Trial Adverse Events Reported in > 5% of Patients and More Commonly in Patients Treated with Piodiab 30 mg + Sulfonylurea than in Patients Treated with Placebo + Sulfonylurea
% of Patients
Placebo + Sulfonylurea N=187	Piodiab 15 mg + Sulfonylurea N=184	Piodiab 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 Piodiab 45 mg + Sulfonylurea than in Patients Treated with Piodiab 30 mg + Sulfonylurea
% of Patients
Piodiab 30 mg + Sulfonylurea N=351	Piodiab 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 Piodiab 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 Piodiab.

Table 3: 16-to 24-Week Clinical Trials of Piodiab Add-on to Metformin

	16-Week Placebo-Controlled Trial Adverse Events Reported in >5% of Patients and More Commonly in Patients Treated with Piodiab + Metformin than in Patients Treated with Placebo + Metformin
% of Patients
Placebo + Metformin N=160	Piodiab 30 mg + Metformin N=168
Edema	2.5	6
Headache	1.9	6
	24-Week Non-Controlled Double-Blind Trial Adverse Events Reported in >5% of Patients and More Commonly in Patients Treated with Piodiab 45 mg + Metformin than in Patients Treated with Piodiab 30 mg + Metformin
% of Patients
Piodiab 30 mg + Metformin N=411	Piodiab 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 Piodiab 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 Piodiab.

Table 4: 16-to 24-Week Clinical Trials of Piodiab Add-on to Insulin

	16-Week Placebo-Controlled Trial Adverse Events Reported in >5% of Patients and More Commonly in Patients Treated with Piodiab 30 mg + Insulin than in Patients Treated with Placebo + Insulin
% of Patients
Placebo + Insulin N=187	Piodiab 15 mg + Insulin N=191	Piodiab 30 mg + Insulin N=188
Hypoglycemia	4.8	7.9	15.4
Edema	7	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 Piodiab 45 mg + Insulin than in Patients Treated with Piodiab 30 mg + Insulin
	% of Patients
	Piodiab 30 mg + Insulin N=345	Piodiab 45 mg + Insulin N=345
Hypoglycemia	43.5	47.8
Edema	22	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 Piodiab than in patients who received placebo.

Table 5: PROactive Trial: Incidence and Types of Adverse Events Reported in > 5% of Patients Treated with Piodiab and More Commonly than Placebo

	% of Patients
Placebo N=2633	Piodiab 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	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 Piodiab 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	Piodiab 15 mg + Sulfonylurea N=184	Piodiab 30 mg + Sulfonylurea N=189	Piodiab 30 mg + Sulfonylurea N=351	Piodiab 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 Piodiab 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	Piodiab 15 mg + Insulin N=191	Piodiab 30 mg + Insulin N=188	Piodiab 30 mg + Insulin N=345	Piodiab 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 Piodiab 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	Piodiab 30 mg + Metformin N=168	Piodiab 30 mg + Metformin N=411	Piodiab 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 Piodiab 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 Piodiab or Glyburide

	Number (%) of Subjects
Piodiab 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	Piodiab 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 Piodiab (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 Piodiab 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 Piodiab 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 Piodiab 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 Piodiab. 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	Piodiab 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 Piodiab 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 Piodiab and placebo in the 16-to 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)	Piodiab 15 mg	Piodiab 30 mg	Piodiab 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 Piodiab Versus Patients Treated with Placebo During the Double-Blind Treatment Period in the PROactive Trial

	Placebo	Piodiab
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 Piodiab and Placebo was 2.7 years.

>

Edema

Edema induced from taking Piodiab is reversible when Piodiab 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 Piodiab is provided in Table 12.

Table 12: Adverse Events of Edema in Patients Treated with Piodiab

		Number (%) of Patients
Placebo	Piodiab 15 mg	Piodiab 30 mg	Piodiab 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	Piodiab 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 Piodiab in the Piodiab controlled clinical trial database to date. One randomized, double-blind 3-year trial comparing Piodiab 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 Piodiab 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 Piodiab in the Piodiab 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 Piodiab 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 Piodiab 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 Piodiab 15 mg, 15.4% with Piodiab 30 mg, and 4.8% with placebo.

The incidence of reported hypoglycemia was higher with Piodiab 45 mg compared to Piodiab 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 Piodiab 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 Piodiab 45 mg in combination with sulfonylurea (n=2) or Piodiab 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. In two 3-year trials in which Piodiab was compared to placebo or glyburide, there were 16/3656 (0.44%) reports of bladder cancer in patients taking Piodiab compared to 5/3679 (0.14%) in patients not taking Piodiab. After excluding patients in whom exposure to study drug was less than one year at the time of diagnosis of bladder cancer, there were six (0.16%) cases on Piodiab and two (0.05%) cases on placebo. There are too few events of bladder cancer to establish causality.

Laboratory Abnormalities

Hematologic Effects

Piodiab may cause decreases in hemoglobin and hematocrit. In placebo-controlled monotherapy trials, mean hemoglobin values declined by 2% to 4% in patients treated with Piodiab 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 Piodiab 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 Piodiab 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 Piodiab (values of 2150 to 11400 IU/L) and in no comparator-treated patients. Six of these nine patients continued to receive Piodiab, two patients were noted to have the CPK elevation on the last day of dosing and one patient discontinued Piodiab due to the elevation. These elevations resolved without any apparent clinical sequelae. The relationship of these events to Piodiab therapy is unknown.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Piodiab. 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 Piodiab, 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.

Piodiab contraindications

See also:
What is the most important information I should know about Piodiab?

You should not use this medication if you are allergic to Piodiab, if you have severe heart failure, if you have active bladder cancer, or if you are in a state of diabetic ketoacidosis (call your doctor for treatment with insulin).

Do not take Piodiab for longer than recommended. Taking this medication for longer than 1 year (12 months) may increase your risk of developing bladder cancer. Talk with your doctor about your specific risk.

Before taking Piodiab, tell your doctor if you have congestive heart failure or heart disease, fluid retention, a history of bladder cancer, a history of heart attack or stroke, or liver disease.

Take care not to let your blood sugar get too low. Low blood sugar (hypoglycemia) can occur if you skip a meal, exercise too long, drink alcohol, or are under stress. Symptoms include headache, hunger, weakness, sweating, tremors, irritability, or trouble concentrating. Carry hard candy or glucose tablets with you in case you have low blood sugar. Other sugar sources include orange juice and milk. Be sure your family and close friends know how to help you in an emergency.

Some women using Piodiab have started having menstrual periods, even after not having a period for a long time due to a medical condition. You may be able to get pregnant if your periods restart. Talk with your doctor about the need for birth control.

Women may also be more likely than men to have bone fractures in the upper arm, hand, or foot while taking Piodiab. Talk with your doctor if you are concerned about this possibility.

Certain oral diabetes medications may increase your risk of serious heart problems. However, not treating your diabetes can damage your heart and other organs. Talk to your doctor about the risks and benefits of treating your diabetes with Piodiab.

Active ingredient matches for Piodiab:

Pioglitazone in Lebanon.

List of Piodiab substitutes (brand and generic names)	Sort by popularity
Unit description / dosage (Manufacturer)	Price, USD
Piodia (South Korea)
Piodib
Piodib 15mg TAB / 10
Piodib 30mg TAB / 10
Piodiglin (Poland)
Piofix
Piofix 15mg TAB / 10	$ 0.30
Piofix 30mg TAB / 10	$ 0.51
Pioforce (Turkey)
Piofox (Turkey)
Piogaz
Piogaz 15mg TAB / 10	$ 0.29
Piogaz 30mg TAB / 10	$ 0.53
PIOGAZ 15MG TABLET 1 strip / 10 tablets each (Ravenbhel Pharmaceuticals Pvt Ltd)	$ 0.34
Piogaz 15mg Tablet (Ravenbhel Pharmaceuticals Pvt Ltd)	$ 0.03
Piogi (South Korea)
PIOGIS (India)
PIOGIS tab 30 mg x 10's (Curis)
Piogla
Piogla 30mg TAB / 10	$ 0.42
Pioglar (India, Peru)
Tablet; Oral; Pioglitazone Hydrochloride 15 mg (Ranbaxy (Stancare))
Tablet; Oral; Pioglitazone Hydrochloride 30 mg (Ranbaxy (Stancare))
Tablet; Oral; Pioglitazone Hydrochloride 45 mg (Ranbaxy (Stancare))
PIOGLAR Capsule/ Tablet / 30mg / 10 units (Ranbaxy (Stancare))	$ 1.18
PIOGLAR Capsule/ Tablet / 15mg / 10 units (Ranbaxy (Stancare))	$ 0.74
Pioglar 15mg TAB / 10 (Ranbaxy (Stancare))	$ 0.77
Pioglar 30mg TAB / 10 (Ranbaxy (Stancare))	$ 1.18
15 mg x 10's (Ranbaxy (Stancare))	$ 0.77
30 mg x 10's (Ranbaxy (Stancare))	$ 1.18
Tablets; Oral; Pioglitazone Hydrochloride 15 mg (Ranbaxy (Stancare))
Tablets; Oral; Pioglitazone Hydrochloride 30 mg (Ranbaxy (Stancare))
Tablets; Oral; Pioglitazone Hydrochloride 45 mg (Ranbaxy (Stancare))
PIOGLAR 15 MG TABLET 1 strip / 10 tablets each (Ranbaxy (Stancare))	$ 1.01
PIOGLAR 30 MG TABLET 1 strip / 10 tablets each (Ranbaxy (Stancare))	$ 1.61
PIOGLAR 7.5 MG TABLET 1 strip / 10 tablets each (Ranbaxy (Stancare))	$ 0.73
PIOGLAR tab 15 mg x 10's (Ranbaxy (Stancare))	$ 0.84
PIOGLAR tab 30 mg x 10's (Ranbaxy (Stancare))	$ 1.35
Pioglar 15mg Tablet (Ranbaxy (Stancare))	$ 0.07
Pioglar 30mg Tablet (Ranbaxy (Stancare))	$ 0.10
Pioglar 7.5mg Tablet (Ranbaxy (Stancare))	$ 0.07
Pioglaz (India)
Pioglaz 15mg TAB / 10 (East West)	$ 0.36
Pioglaz 30mg TAB / 10 (East West)	$ 0.54
15 mg x 10's (East West)	$ 0.36
30 mg x 10's (East West)	$ 0.54
PIOGLAZ 15MG TABLET 1 strip / 10 tablets each (East West)	$ 0.46
PIOGLAZ 30MG TABLET 1 strip / 10 tablets each (East West)	$ 0.71
PIOGLAZ tab 15 mg x 10's (East West)	$ 0.36
See 1539 substitutes for Piodiab

References

1. PubChem. "Pioglitazone". https://pubchem.ncbi.nlm.nih.gov/com... (accessed September 17, 2018).
2. DrugBank. "Pioglitazone". http://www.drugbank.ca/drugs/DB01132 (accessed September 17, 2018).
3. DTP/NCI. "pioglitazone hydrochloride: The NCI Development Therapeutics Program (DTP) provides services and resources to the academic and private-sector research communities worldwide to facilitate the discovery and development of new cancer therapeutic agents.". https://dtp.cancer.gov/dtpstandard/s... (accessed September 17, 2018).

Reviews

The results of a survey conducted on ndrugs.com for Piodiab are given in detail below. The results of the survey conducted are based on the impressions and views of the website users and consumers taking Piodiab. We implore you to kindly base your medical condition or therapeutic choices on the result or test conducted by a physician or licensed medical practitioners.

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Information checked by Dr. Sachin Kumar, MD Pharmacology