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Competact Review Article

 

Adimet Competact (Actoplus Met) approved in 2005. Itís a combination therapy with two active components, pioglitazone (a thiazolidinedione) and metformin (a biguanides). Both drugs are classified as insulin sensitizers. It is the first and only fixed-dose combination approved with the extended release form of metformin. It is used for the treatment of type 2 diabetes mellitus,

Prior to approval, this drug did not have any efficacy studies. But its separate components, metformin and pioglitazone, have long been established for its safety and efficacy. The separate approvals of the two drugs were used as the combination drugís basis for approval. Concerns regarding the combination drug were addressed with two clinical studies proving that co administration of the two tablets (Glucophage and Actos) is safe and effective. A study made by Seufert (2006) has found that the two separate drugs is bioequivalent with a single Competact.

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15 mg / 850 mg 56 tab USD 169.00 Add to Basket
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Type 2 Diabetes, also called as Non Insulin Dependent Diabetes Mellitus, is a type of diabetes in caused by increased insulin sensitivity with decreased insulin secretion by β cells. This results to high levels of sugar in the blood. Diabetes type 2 is the most common form of diabetes, accounting for 90% of all diabetic patients.

Several complications may arise if diabetes is not managed properly. There are four dangerous complications of diabetes. These include peripheral neuropathy, which leads to diabetic foot ulcer and eventual amputation; nephropathy which usually develops to chronic kidney failure; retinopathy which leads to blindness; and cardiovascular problems like stroke and heart attack.

Diabetic foot ulcer In 2003, it is estimated that almost 150 million people have type 2 diabetes, and by 2025 this number will double (Green, 2003). In 2007, it was estimated that the world wide cost of medication (both treatment and prevention) for this disease was about $232 billion dollars, which is estimated to increase by $302.5 billion by 2025.

Combination Drug

Being a combination drug, Competact (Actoplus Met) possesses the efficacy of its two agents. Though they are both insulin sensitizers, they possess different mechanisms of action. Pioglitazone increases glucose utilization of muscles while metformin decreases hepatic glucose production.

Pioglitazone, being a thiazolidinedione, acts by binding to (PPARy) or peroxisome proliferator-activated receptors gamma. This receptor is found on the membrane of skeletal muscle and fat cells. PPARy mediates the metabolism and utilization of glucose into cells, leading to blood glucose lowering.

Metformin, on the other hand, belongs to the biguanides. Studies made by Stumvoll et al., (1995), Schafer (1983) and Hundal et al., (2000) suggest that metformin act by suppression of glucose production through activation of AMPK. AMPK activation produces insulin-like effects (Lochhead, et al., 2000), which leads to glucose level reduction.

Efficacy of Combination Therapy for Diabetes

Several studies have mentioned that combination therapy is advantageous and desired for patients with poor glycemic control. Studies made by Fonseca et al. (2000), Einhorn et al. (2000), and others have all stated that a combination of a thiazolidinedione and metformin produces a significant reduction in glucose levels. Glycemic control deteriorates with time. Thus, with the use of two drugs with complimentary mechanisms of glucose control, patients receive better glucose control.

Seufert and colleagues (2006) states that a combination therapy of pioglitazone and metformin is a rational approach to treating diabetes type 2.

Adverse effects

Though the use of combination therapy is desirable, however, it is not always advisable. Before using this drug, it is highly recommended to consult with a physician. Because this is a combination drug, two drugs are then a plausible source of side effects. The risks are also doubled, should they have a similar side effect. Some of the side effects known for this drug are upper respiratory tract infection, nausea, headache, diarrhea, UTI, sinusitis, dizziness, edema, and weight gain. More notorious side effects include lactic acidosis (metformin) and cardiovascular problems (pioglitazone).

Dosing

Below the recommended initial dosing for three different cases, like patients from metformin, patients from pioglitazone, or patients from combination of pioglitazone and metformin on separate tablets shifting to Competact (Actoplus Met).

Patient Class:From metformin
Dose: 15mg/500mg or 15mg/850mg OD or BID, gradually titrated

From pioglitazone
Dose: 15mg/500mg BID, or 15mg/850mg OD, gradually titrated

From metformin plus pioglitazone
Dose: 15mg/500mg or 15mg/850mg OD or BID, gradually titrated

Conclusion

In conclusion, Competact is a combination drug used for poorly controlled diabetes mellitus type 2. It possesses two drugs as active ingredient, pioglitazone and metformin which are both effective for treating type 2 diabetes. Caution is advised to patients due to the increased risk of adverse effects.

Bibliography

Einhorn, D., Rendell, M., Rosenzweg, J., et al., 2000, Pioglitazone hydrochloride in combination with metformin in the treatment of type 2 diabetes mellitus: A randomized, placebo-controlled study

Fonseca, V., Rosenstock, J., Patwardhan, R., Salzman, A., 2000, Effect of Metformin and Rosiglitazone Combination Therapy in Patients With Type 2 Diabetes Mellitus

Green, A., Chirstian Hirsch, N., and Pramming, S. K., 2003, The changing world demography of type 2 diabetes

Hundal, R. S., et al., 2000, Mechanism by which metformin reduces glucose production in type 2 diabetes, Diabetes. 49:2063-2069

Lochhead, P. A., Salt, I.P., Walker, K. S., Hardie, D. G., and Sutherland, C., 2000, 5- aminoimidazole-4-carboxamide riboside mimics the effects of insulin on the expression of the 2 key gluconeogenic genes PEPCK and glucose-6-phosphatase, Diabetes. 49:896Ė903

Schafer, G., 1983, Biguanides. A review of history, pharmacodynamics and therapy, Diabete Metab. 9:148-163

Seufert, J., 2006, A fixed-dose combination of pioglitazone and metformin:a promising alternative in metabolic control
Stumvoll, M., Nurjhan, N., Perriello, G., Dailey, G., and Gerich, J. E., 1995, Metabolic effects of metformin in non-insulin-dependent diabetes mellitus, N. Engl J. Med. 333:550-554


 

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