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T2D Medicine Thiazolidinedione

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T2D Medicine Thiazolidinedione

Actos, Avandia (Thiazolidinedione) diabetes medicines help the body to utilize the insulin properly; thus blood-glucose level stay on target and body cells get the energy they needed.

Thiazolidinedione increases insulin-stimulated glucose uptake in skeletal muscle cells. In addition to lowering glycemia, these agents modestly reduce blood pressure, increases high-density lipoprotein cholesterol (HDL), decreases triglyceride, enhance fibrinolysis, and improve endothelial function.

Thiazolidinediones is suitable as a mono-therapy and in combination with metformin, sulfonylureas, and insulin. Additionally, combining two sensitizers from different drug classes (pioglitazone and metformin or rosiglitazone and metformin) produces an additive effect. They can combine with another class of drugs (sulphonylureas or metformin) to improve glucose control.

Thiazolidinedione’s mechanism of action

Thiazolidinediones acts primarily by improving insulin sensitivity in muscle and adipose tissue and inhibit hepatic gluconeogenesis.

They act on the peroxisome proliferator-activated receptor-gamma (PPAR-γ) which regulates the transcription of insulin responsive genes and fatty acid metabolism. Improvement in glycemic control may be apparent after six weeks of treatment and maximal effect up to six months.

Thiazolidinedione’s diabetes medications

  • Generic name: Pioglitazone (Brand names: Actos in Australia, United Kingdom, Philippines, United States, Canada;  Diabetone, Glitaz, Glitter, Glucozone, Insulact, Piotaz, Piouno, Piozar, Piozone, PPAR, Prialta, Pyoglit, Zolid, Zypi in Philippines; Diavista, Glito, Glizone, G-Tase, K-Pio, Lita, Path, Pepar, P-Glitz, Pioglar, Pioglaz, Pioglit, Pionorm, Pio-Q, Piostar, Piosys, Piotrol, Pioz, Piozed, Piozone, Pizorad, Pozitiv, Radizone, Zipio in India; Apo-Pioglitazone, CO Pioglitazone, Gen-Pioglitazone, Pioglitazone Hydrochloride Accord, PMS-Pioglitazone, ratio-Pioglitazone, Sandoz Pioglitazone in Canada; Pioglitazone Consilient in United Kingdom)
  • Generic name: Rosiglitazone (Brand names: Avandia in Australia, Canada, United States, United Kingdom, and other countries)

Thiazolidinedione dosage

Rosiglitazone minimum dose is 4 mg once daily and maximum dose is 4 mg twice daily. Pioglitazone minimum dose is 15 mg once daily and maximum dose is 45 mg once daily.

Rosiglitazone and Metformin fixed combination minimum dose 2 mg Rosiglitazone and 500 mg Metformin, maximum dose 4 mg Rosiglitazone and 500 mg Metformin.

Side effects of TZDs

The most common side effect of all thiazolidinediones is water retention, leading to edema, a problem in less than 5% of individuals. Significant water retention may lead to a decompensation of potentially, previously unrecognized heart failure.

Studies have shown that there is an increased risk of coronary heart disease and heart attacks with rosiglitazone. However, pioglitazone has shown significant protection from both micro and macro-vascular cardiovascular events and plaque formation.

What you can expect from Thiazolidinediones?

Thiazolidinediones decrease fasting plasma glucose (FPG) by 35 to 40 mg/dl or 1.94 to 2.22 mmol/l and lower hemoglobin A1C by 0.5 to 1.5%, the same degree as metformin and sulfonylureas, and to a greater degree than alpha-glucosidase inhibitors.

When used as a mono-therapy, both rosiglitazone and pioglitazone have not been associated with hypoglycemia, 1 to 4 kgs (2lb 3.274oz to 8ld 13.096oz) weight gain. Additionally, it raises HDL; however, it may also slightly raise LDL cholesterol with minimal effect on triglyceride concentrations. It may cause increases in plasma volume that result in edema and small decreases in hemoglobin and hematocrit. The clearance of this drug is decreasing in patients with moderate to severe liver disease; thus, carryout liver function tests every two months for the first year, thereafter periodically.

Who can benefit from Thiazolidinediones?

Pioglitazone demonstrated modest improvement in the composite outcome of all-cause mortality, nonfatal myocardial infarction, and stroke in patients with type d diabetes. Diabetes Reduction Assessment with Ramipril and Rosiglitazone Medications (DREAM) trial demonstrate a significant (62%) reduction in the progression to diabetes mellitus in high-risk patients treated with rosiglitazone.

Who should avoid using Thiazolidinediones

Adverse effects of thiazolidinediones include weight gain, edema, anemia, and peripheral fractures in women. Weight gain and edema are more common among patients treated with thiazolidinediones and insulin. The FDA still recommends periodic measurement of hepatic function in patients treated with TDZs. Patients with congestive heart failure or hepatic impairment should avoid taking this drug.

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