Dieta Plus30 mg+4 mg

Dieta Plus is a fixed-dose combination antidiabetic medicine used in the management of type 2 diabetes mellitus, indicated as an adjunct to diet and exercise to improve glycemic control.

• Established/approved use: Dieta Plus is indicated for patients with type 2 diabetes mellitus who are already being treated with a thiazolidinedione and a sulfonylurea, or whose blood glucose is not adequately controlled with a sulfonylurea alone, or who have initially responded to pioglitazone monotherapy and require additional glycemic control from a sulfonylurea.
• Combination-therapy requirement: Dieta Plus is intended for patients who require dual-mechanism therapy (an insulin sensitizer plus an insulin secretagogue) and is not intended as first-line monotherapy for newly diagnosed type 2 diabetes.
• Not indicated for: type 1 diabetes mellitus or diabetic ketoacidosis, in which Dieta Plus has no established role.

Pioglitazone + Glimepiride is available as an oral tablet combining two active pharmaceutical ingredients:

• Pioglitazone (as pioglitazone hydrochloride) — a thiazolidinedione insulin-sensitizer.
• Glimepiride — a second-generation sulfonylurea insulin secretagogue.

Common fixed-dose strengths of Pioglitazone + Glimepiride include Pioglitazone 15 mg/Glimepiride 1 mg, Pioglitazone 15 mg/Glimepiride 2 mg, Pioglitazone 30 mg/Glimepiride 2 mg, and Pioglitazone 30 mg/Glimepiride 4 mg; exact available strengths vary by manufacturer.

Dieta Plus is an oral fixed-dose combination medicine used in adults with type 2 diabetes mellitus. It combines a thiazolidinedione (pioglitazone), which improves the body's sensitivity to insulin in muscle and fat tissue and reduces hepatic glucose output, with a sulfonylurea (glimepiride), which stimulates the pancreas to release more insulin.

By acting through two complementary mechanisms, Dieta Plus helps lower blood glucose more effectively than either component alone in appropriately selected patients, and is used as part of a broader treatment plan that includes diet, exercise, and regular blood glucose monitoring.

Antidiabetic combination — Dieta Plus belongs to the thiazolidinedione (TZD) plus sulfonylurea class of oral antidiabetic agents.

Mechanism of Action

Pioglitazone + Glimepiride combines two agents with complementary and distinct mechanisms of glucose lowering:

• Pioglitazone is a thiazolidinedione that acts as a selective agonist at the peroxisome proliferator-activated receptor-gamma (PPAR-γ). Activation of PPAR-γ increases insulin sensitivity in skeletal muscle and adipose tissue and reduces hepatic glucose production, without directly stimulating insulin secretion.
• Glimepiride is a sulfonylurea that binds to ATP-sensitive potassium channels on pancreatic beta-cell membranes, causing depolarization and calcium influx, which triggers insulin release from the pancreas. It may also have modest extrapancreatic insulin-sensitizing effects.

Pharmacokinetics

Both components of Pioglitazone + Glimepiride are well absorbed orally, extensively bound to plasma proteins, and metabolized primarily in the liver via cytochrome P450 pathways (pioglitazone mainly via CYP2C8, glimepiride mainly via CYP2C9), with elimination via bile/feces (pioglitazone) and urine/feces (glimepiride metabolites).

Dieta Plus should be taken orally, once daily, with the first main meal of the day to reduce the risk of gastrointestinal upset and hypoglycemia. Tablets should be swallowed whole with a glass of water and not crushed or chewed unless otherwise directed. Doses should not be doubled if a dose is missed; the next dose should be taken at the usual time.

Dieta Plus has clinically important interactions related to both of its components:

• Gemfibrozil (a CYP2C8 inhibitor) can substantially increase pioglitazone exposure; concomitant use requires dose caution and limitation of the pioglitazone component of Dieta Plus.
• Rifampicin and other strong CYP2C8/CYP2C9 inducers can reduce plasma levels of both components of Dieta Plus, potentially reducing glycemic control.
• Insulin: combined use with Dieta Plus increases the risk of fluid retention and heart failure and is generally not recommended, especially in patients with or at risk of heart failure.
• Other antidiabetic agents and alcohol: concurrent use increases the risk of hypoglycemia from the glimepiride component of Dieta Plus.
• Beta-blockers and certain other sympatholytic drugs may mask the warning signs and symptoms of hypoglycemia caused by the glimepiride component of Dieta Plus.
• CYP2C9 inhibitors (e.g., fluconazole) may increase glimepiride levels and hypoglycemia risk, while CYP2C9 inducers may reduce efficacy.

Side effects of Dieta Plus may arise from either component:

See Precautions and Warnings for detail on serious risks associated with Dieta Plus.

Pregnancy: Dieta Plus is not recommended during pregnancy. Insulin is generally preferred for glycemic control in pregnant women with diabetes. Dieta Plus should be used only if clearly needed and if the potential benefit justifies the potential risk to the fetus; a physician should be consulted before use in pregnancy or if pregnancy is suspected.

Lactation: It is not known whether the components of Dieta Plus are excreted in human breast milk; because of the potential for hypoglycemia in a nursing infant, Dieta Plus is not recommended during breastfeeding unless a physician determines the benefit outweighs the risk.

Note: in premenopausal, anovulatory women, the pioglitazone component of Dieta Plus may result in resumption of ovulation, increasing the risk of unintended pregnancy; adequate contraception should be discussed with a physician.

Boxed Warning: Heart Failure

The pioglitazone component of Dieta Plus can cause or worsen congestive heart failure. Dieta Plus is contraindicated in patients with NYHA Class III or IV heart failure. Patients should be monitored for signs and symptoms of heart failure (rapid weight gain, edema, shortness of breath), particularly after starting Dieta Plus or increasing its dose.

Other Warnings

• Bladder cancer: pioglitazone has been associated with an increased risk of bladder cancer in some studies; Dieta Plus should be avoided in patients with active bladder cancer and used with caution in those with a prior history.
• Hypoglycemia: the glimepiride component of Dieta Plus can cause hypoglycemia, particularly with missed meals, alcohol use, strenuous exercise, renal or hepatic impairment, or in elderly patients; patients should be educated on recognizing and managing low blood sugar.
• Fluid retention, edema, and macular edema: Dieta Plus may cause or worsen fluid retention; new or worsening visual disturbance should prompt ophthalmologic evaluation for macular edema.
• Bone fracture risk: an increased incidence of bone fractures, particularly in women, has been reported with thiazolidinediones such as the pioglitazone component of Dieta Plus.
• Hepatic effects: baseline and periodic liver function monitoring is reasonable during treatment with Dieta Plus; therapy should be discontinued if significant liver injury is suspected.
• Hemolytic anemia: patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency may be at risk of hemolytic anemia with the sulfonylurea component of Dieta Plus; a non-sulfonylurea alternative should be considered in such patients.
• Alcohol: alcohol should be avoided or limited during treatment with Dieta Plus, as it can increase the risk of hypoglycemia and, historically, sulfonylureas have been associated with disulfiram-like reactions in some patients.

Overdose of Dieta Plus may present primarily with hypoglycemia (from the glimepiride component), with symptoms such as sweating, tremor, confusion, or loss of consciousness, and potentially with fluid retention or edema (from the pioglitazone component). If an overdose of Dieta Plus is suspected, seek immediate medical attention or contact a poison control center right away; mild hypoglycemia can be managed with oral glucose, but severe or persistent symptoms require emergency medical care and close monitoring.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

• Renal impairment: the glimepiride component of Dieta Plus should be initiated at the lowest dose with careful titration in patients with renal impairment due to increased hypoglycemia risk.
• Hepatic impairment: Dieta Plus is not recommended in patients with significant hepatic impairment; see Contraindications.
• Elderly: elderly patients are at increased risk of hypoglycemia and heart failure with Dieta Plus and should be dosed conservatively with close monitoring.
• Pregnancy and lactation: see the Pregnancy and Lactation section.
• Pediatric use: see Pediatric Uses section.

Dieta Plus is generally used as long-term, ongoing therapy for chronic management of type 2 diabetes mellitus, with periodic reassessment of glycemic control (e.g., HbA1c), liver function, cardiac status, and overall tolerability by the treating physician to determine continued suitability of therapy.

Pioglitazone + Glimepiride is classified as a thiazolidinedione (TZD) insulin-sensitizer combined with a second-generation sulfonylurea insulin secretagogue.

Pioglitazone + Glimepiride lowers blood glucose through two complementary actions: pioglitazone activates PPAR-γ receptors to improve peripheral insulin sensitivity and reduce hepatic glucose production, while glimepiride stimulates pancreatic beta-cells to release insulin by closing ATP-sensitive potassium channels. Together, these actions in Pioglitazone + Glimepiride address both insulin resistance and insufficient insulin secretion in type 2 diabetes.

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The safety and efficacy of Dieta Plus in pediatric patients (under 18 years of age) have not been established. Dieta Plus is not recommended for use in children and adolescents, and alternative, pediatric-appropriate antidiabetic therapy should be used under specialist guidance.