JANUMET ® a drug based on Sitagliptin and Metformin
THERAPEUTIC GROUP: Associated oral hypoglycemic agents
IndicationsAction mechanismStudies and clinical effectiveness Usage and dosage instructionsWarnings Pregnancy and lactationInteractionsContraindicationsUndesirable effects
Indications JANUMET ® - Sitagliptin + Metformin
JANUMET ® is used in the treatment of type II diabetes, when only metformin therapy, even at the highest dose, was not able to guarantee good glycemic control.
In patients with severe metabolic decompensation, JANUMET ® may be included in the triple therapy with sulfonylurea.
Mechanism of action JANUMET ® - Sitagliptin + Metformin
JANUMET ® is an oral hypoglycemic drug, obtained by combining active ingredients belonging to the DPP-4 and biguanide inhibitors category.
The therapeutic effect, which is carried out through an integrated control of glucose metabolism, is mediated by sitagliptin, able to increase the availability of incretins (reducing the activation of DPP-4, involved in irreversible hydrolysis), hormones dedicated to sensitization of the pancreatic beta cell useful to ensure the release of insulin, and of metformin, able to act on various sensitive insulin tissues by increasing blood glucose uptake, and to the liver level by inhibiting the process of gluconeogenesis and glycogenolysis.
From a metabolic point of view, therefore, the hypoglycemic effect is on the one hand supported by the increased secretion of insulin and on the other by the reduced endogenous production of glucose.
From the pharmacokinetic point of view, the intake of JANUMET ® maintains the characteristics of the two active ingredients taken individually, almost unchanged.
Studies carried out and clinical efficacy
1. THE EFFECTIVENESS OF COMBINED SITAGLIPTIN / METFORMIN THERAPY
Studies have shown that the association between metformin and sitagliptin can ensure good glycemic control in those patients with type II diabetes mellitus, for whom metformin-only therapy was ineffective. In these cases, a further reduction in glycosylated hemoglobin was observed, excellent glycemic control, both basic and post-prandial, and a reduced risk of hypoglycemia.
2. SITAGLIPTIN / METFORMIN, BEYOND THE CLINICAL PRACTICE
The important therapeutic successes that the association between metformin and sitagliptin has gained in clinical practice seem essentially associated with the individual therapeutic effects of the two active ingredients. However, in vitro studies have shown that this combination can act synergistically on the beta cell, preserving function and integrity, probably by activating anti-apoptotic genes involved in cell survival.
3. SITAGLIPTIN / METFORMIN IN A SINGLE FORMULATION
Pharmacokinetic studies and clinical trials of various nature, have concluded that the therapeutic effect observable following the intake of JANUMET, can be completely comparable to that obtained with the separate but simultaneous administration of metformin and sitagliptin, with the same frequency of side effects.
Method of use and dosage
JANUMET ® 50/850 or 50/1000 mg tablets of sitagliptin and metformin:
JANUMET ® therapy should start from the minimum dose that can be administered, to then eventually correct or validate the aforementioned dosage, based on the metabolic response observed in terms of blood glucose concentration.
The maximum dose should not exceed that of 100 mg of sitagliptin, possibly taken in two different doses concomitantly with meals to reduce gastrointestinal side effects.
In the event that triple therapy with sulfonylureas is used, lower dosages could also be used.
In any case, it is up to your doctor to evaluate and formulate the appropriate dosage.
Warnings JANUMET ® - Sitagliptin + Metformin
It is very important in ensuring correct glycemic control, that treatment with JANUMET ® is accompanied by periodic monitoring of glycemic levels and the concomitant application of non-pharmacological measures such as physical activity and a balanced diet.
It is also necessary to monitor renal function to prevent the accumulation of metformin from inducing a potentially lethal state of metabolic acidosis in the patient.
Treatment with JANUMET ® should be suspended in cases where the use of iodinated contrast media is required, or of drugs or procedures that could compromise renal function.
Hypoglycaemia conditions, potentially verifiable following incorrect dosages, administration of active ingredients or other causes, could reduce the patient's perceptive and reactive capacities, making the use of machinery and driving vehicles dangerous.
PREGNANCY AND BREASTFEEDING
The use of JANUMET ® in pregnancy is strongly contraindicated, due to the presence of studies showing an increased risk of congenital malformations in newborns born to women treated with metformin.
On the contrary, experimentation with sitagliptin does not currently produce statistically significant results.
Furthermore, the possible secretion of these active ingredients in breast milk exposes the infant to the potential risk of hypoglycemia, so as to extend the contraindication also to the period of breastfeeding.
Interactions
Also in this case the pharmacological interactions observed for JANUMET ® are to be attributed separately to the presence of the two active ingredients.
Consequently, while sitagliptin is not very reactive, with pharmacokinetic changes observable following the administration of digoxin and ciclosporin, metformin could respond negatively to the concomitant administration of glucorticoids, beta agonists, cimetidine, and diuretics.
Several studies have also evaluated the presence of other possible in vitro interactions, which however assume a modest clinical relevance in vivo.
It is also useful to remember that the concomitant administration of rifampicin or iodinated contrast agents could alter normal renal function, increasing the body's exposure to these hypoglycemic drugs.
Contraindications JANUMET ® - Sitagliptin + Metformin
JANUMET ® is contraindicated in case of hypersensitivity to the active ingredients or excipients, type I diabetes, diabetic keto acidosis, severe changes in liver and kidney function, dehydration, shock, acute pathologies, heart and respiratory failure, shock, alcoholism, pregnancy and lactation .
Undesirable effects - Side effects
The side effects described following therapy with JANUMET ® are essentially attributable to those observed during monotherapy with sitagliptin and metformin.
Above all, the initial phase of therapy may be accompanied by gastrointestinal disorders such as nausea, vomiting, constipation or diarrhea, upper respiratory tract infections and headache and dizziness.
Clinically more significant adverse reactions have been observed only rarely, with the appearance of hypersensitivity reactions such as angioedema, rash and urticaria, alterations of the hematological and electrocardiographic pattern, for which it was necessary to suspend therapy.
Hypoglycemia conditions, on the other hand, occurred mainly during triple therapy with sulfonylureas.
Note
JANUMET ® can only be sold under strict medical prescription
