alogliptin/pioglitazone

Action and Spectrum

Mechanism of action

alogliptin: It is a DPP-4 (dipeptidyl peptidase-4) inhibitor. DPP-4 is an enzyme that breaks down incretin hormones, which regulate insulin secretion and glucose metabolism. By inhibiting DPP-4, alogliptin increases the levels of incretin hormones, leading to increased insulin secretion and improved glucose metabolism.

pioglitazone: It is a member of the thiazolidinedione class of antidiabetic drugs known as glitazones. pioglitazone works by increasing insulin sensitivity, mainly in muscle and liver cells. This leads to improved glucose uptake and storage in these cells, leading to improved glycemic control.

The combination of alogliptin and pioglitazone provides a dual mechanism of action, improving glycemic control through increased insulin secretion and sensitivity.

Spectrum

The spectrum of activity of alogliptin/pioglitazone is primarily limited to treating type 2 diabetes in adults. It is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. It is essential to use alogliptin/pioglitazone as directed by a healthcare provider and to follow their instructions to minimize the risk of side effects.

Drug Interaction

Adverse Reaction

Frequency defined:

>10%

Edema

Worsening CHF

1-10%

Nasopharyngitis

Upper respiratory tract infections

Hypoglycemia

Back pain

<1%

Pancreatitis

Hypersensitivity

Post-marketing reports

Anaphylaxis

Rash

Constipation

Nausea

Ileus

Urticaria

Rhabdomyolysis

Nephritis

Arthralgia

Hepatic enzyme elevations

Black Box Warning

Black box warning

The warning states that studies have shown an increased risk of bladder cancer in patients taking pioglitazone, one of the active ingredients in alogliptin/pioglitazone. The risk of bladder cancer increases with a more extended use duration and higher cumulative doses of pioglitazone.

The FDA has also issued warnings about the potential for liver injury and heart failure with pioglitazone. Patients taking alogliptin/pioglitazone should be monitored regularly for liver function changes and heart failure symptoms. Suppose you experience any liver injury or heart failure symptoms, such as abdominal pain, yellowing of the skin or eyes, or shortness of breath. In that case, you should contact your healthcare provider immediately

Contraindication / Caution

Contraindications

• Hypersensitivity to alogliptin, pioglitazone, or any of the excipients in the formulation
• Acute conditions affecting the heart, liver, or pancreas, such as heart failure, liver disease, or acute pancreatitis
• Alcoholism or uncontrolled alcohol intake
• Severe hepatic impairment
• Pregnancy and breastfeeding
• Edema or fluid retention due to heart failure or liver disease

Caution

• Cardiovascular disease: This medication may increase the risk of heart failure, especially in patients with a history of heart disease or those taking medications that can cause fluid retention.
• Bone fractures: In combination with medication, it may increase the risk of bone fractures, particularly in women.
• Liver function: It may cause elevations in liver function tests. Monitoring of liver function is recommended, especially in patients with liver disease.
• Bladder cancer: It has been associated with an increased risk of bladder cancer in some studies. Regular monitoring of patients is recommended.
• Hypoglycemia: The combination medication may increase the risk of low blood sugar (hypoglycemia) in patients taking insulin or insulin secretagogues.
• Edema: It may cause fluid retention, which can lead to edema

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available

Lactation: Excretion of the drug in human breast milk is unknown

Pregnancy category:

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women.

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology

• Alogliptin: It is a selective DPP-4 inhibitor, which slows the inactivation of incretin hormones such as GLP-1 and GIP, leading to increased insulin secretion and reduced glucose production by the liver
• Pioglitazone: It is a thiazolidinedione that improves the response of target cells to insulin and decreases gluconeogenesis in the liver. When used together, the combination of alogliptin and pioglitazone can provide greater glucose control compared to either drug used alone

Pharmacodynamics

• alogliptin: It slows the inactivation of incretin hormones, such as glucagon-like peptide 1 (GLP-1), by inhibiting the activity of the enzyme dipeptidyl peptidase-4 (DPP-4). This increases the concentration and action of incretin hormones, leading to an increase in insulin secretion and a decrease in glucagon secretion. These actions result in reduced fasting and postprandial glucose concentrations in a glucose-dependent manner.
• pioglitazone: It is a thiazolidinedione that improves insulin sensitivity by increasing the expression of genes involved in insulin signaling and glucose uptake in target tissues such as muscle, liver, and fat. It also decreases hepatic gluconeogenesis, which is the production of glucose by the liver.

Pharmacokinetics

• Absorption: It has a bioavailability of about 100% and is rapidly absorbed after oral administration, with a peak plasma time of 1-2 hours. Pioglitazone is rapidly absorbed after oral administration, with a peak plasma time of 2-4 hours.
• Distribution: It is 20% protein bound, and its volume of distribution (Vd) is 417 L. Pioglitazone is highly protein bound (>99%) and has a Vd of 0.63 L/kg.
• Metabolism: It does not undergo extensive metabolism and is primarily excreted unchanged in the urine. Pioglitazone is metabolized to active metabolites by hepatic CYP2C8 and CYP3A4.
• Elimination: It has a half-life of 21 hours, with a renal clearance of 9.6 L/hr and a total body clearance of 14 L/hr. Most of the drug is eliminated through the kidneys, with some excretion in the feces. Pioglitazone has a half-life of 3-7 hours and is primarily eliminated through the urine, with 15-30% of the dose excreted in this manner

Adminstartion

Administration

alogliptin/pioglitazone can be taken with or without food and should be swallowed whole without chewing, splitting, or crushing. This is because the medication is formulated as a tablet to release its active ingredients gradually.

If the tablet is chewed, split, or crushed, the active ingredients may be released too quickly, affecting the drug’s efficacy and increasing the risk of side effects. Taking the tablet whole, as directed, will help ensure that the active ingredients are absorbed into the body at the proper rate for optimal therapeutic effect

Patient Information Leaflet

Patient information leaflet

Generic Name: alogliptin/pioglitazone

Pronounced: [ AL-oh-GLIP-tin-and-PYE-oh-GLI-ta-zone ]

Why do we use alogliptin/pioglitazone?

It is used as an oral medication for the treatment of type 2 diabetes