Vildagliptin acts primarily by inhibiting DPP-4 (Dipeptidyl
peptidase-4), the enzyme responsible for the degradation of the incretin
hormones GLP-1 (glucagon-like peptide-1) and GIP (glucose-dependent
insulinotropic polypeptide). The administration of Vildagliptin results in a
rapid and complete inhibition of DPP-4 activity resulting in increased fasting
and postprandial endogenous levels of the incretin hormones GLP-1 and GIP. By
increasing the endogenous levels of these incretin hormones, Vildagliptin
increases insulin secretion from the pancreatic beta-cell and decreases
glucagon secretion from the alpha cells. The enhanced increase in the
insulin/glucagon ratio during hyperglycaemia due to increased incretin hormone
levels results in a decrease in fasting and postprandial hepatic glucose
production, leading to reduced glycaemia.
Metformin Hydrochloride is a biguanide type oral
antihyperglycemic drug used in the management of type 2 diabetes. It lowers
both basal and postprandial plasma glucose. Its mechanism of action is
different from those of sulfonylureas and it does not produce hypoglycemia.
Glucomin decreases hepatic glucose production decreases intestinal absorption
of glucose and improves insulin sensitivity by an increase in peripheral glucose
uptake and utilization.
Adults: Based on the patient's current dose of Metformin, this
combination may be initiated twice daily, with 1 tablet in the morning and the
other in the evening. Patients receiving Vildagliptin and Metformin from
separate tablets may be switched to this combination containing the same doses
of each component. Doses higher than 100 mg of vildagliptin are not
recommended. There is no clinical experience of Vildagliptin and Metformin in
triple combination with other antidiabetic agents. Taking this combination with
or just after food may reduce gastrointestinal symptoms associated with
Metformin.
No clinically relevant pharmacokinetic interaction was observed
when Vildagliptin (100 mg once daily) was co-administered with Metformin
Hydrochloride (1,000 mg once daily). Vildagliptin has a low potential for drug
interactions. Since Vildagliptin is not a cytochrome P (CYP) 450
enzyme-substrate nor does it inhibit nor induce CYP 450 enzymes, it is not likely
to interact with co-medications that are substrates, inhibitors or inducers of
these enzymes. As a result of these studies no clinically relevant interactions
with other oral antidiabetics (glibenclamide, pioglitazone, metformin
hydrochloride), amlodipine, digoxin, ramipril, simvastatin, valsartan or
warfarin were observed after co-administration with vildagliptin. On the other
hand, furosemide, nifedipine and glyburide increase Cmax and blood AUC of
Metformin with no change in renal clearance of Metformin.
This combination is contraindicated in patients with known
hypersensitivity to Vildagliptin or Metformin Hydrochloride or to any of the
excipients. It is contraindicated in patients with renal disease or renal
dysfunction, acute myocardial infarction, and septicaemia. It is also
contraindicated in patients with congestive heart failure patients and in
patients with acute or chronic metabolic acidosis, including diabetic
ketoacidosis, with or without coma. It should be temporarily discontinued in
patients undergoing radiologic studies involving intravascular administration
of iodinated contrast materials, because the use of such products may result in
acute alteration of renal function.
The most common side effects are headache, tremor, dizziness,
nausea, hypoglycaemia etc.
There are no adequate and well-controlled studies in pregnant
women and therefore, this combination should not be used during pregnancy
unless the potential benefit justifies the potential risk to the foetus. No
studies have been conducted on the components of this combination. As it is not
known whether Vildagliptin and/or Metformin Hydrochloride is excreted in human
milk this combination should not be administered to breastfeeding women.
Lactic acidosis can occur due to Metformin accumulation. If
metabolic acidosis is suspected, treatment should be discontinued and the
patient should be hospitalized immediately. Serum creatinine should be
monitored at least once a year in patients with normal renal function and 2–4
times a year in patients with serum creatinine levels at the upper limit of
normal and in elderly patients. Special caution should be exercised in elderly
patients where renal function may become impaired (e.g. when initiating
antihypertensives, diuretics or NSAIDs). It is recommended that Liver Function
Tests (LFTs) are monitored prior to initiation of this drug, at three-monthly
intervals in the first year and periodically thereafter. If transaminase levels
are increased, patients should be monitored with a second liver function
evaluation to confirm the finding and be followed thereafter with frequent
liver function tests until the abnormality return to normal. If AST or ALT
persist at 3 x ULN, Vildagliptin & Metformin tablets should be stopped for
Patients who develop jaundice or other signs of liver dysfunction. Following
the withdrawal of treatment with Vildagliptin & Metformin and LFT
normalization, treatment with Vildagliptin & Metformin should not be reinitiated.
Vildagliptin & Metformin tablets should be discontinued 48 hours before
elective surgery with general anaesthesia and should not usually be resumed
earlier than 48 hours afterwards.
Combination Oral hypoglycemic preparations
Keep in a dry place away from light and heat. Keep out of the reach of children
