PHARMACOLOGY

Pharmacotherapeutic Group: Anti-Diabetic

 Pharmacodynamic properties: Sitagliptin is highly selective inhibitor of dipeptidyl peptidase-4 (DPP-4) enzyme that act as incretin enhancer. Metformin is a biguanide  that decreases blood glucose level by decreasing by decreasing hepatic glucose production,decreasing intestinal absorption of glucose & improving insulin sensitivity by increasing peripheral glucose uptake and utilization. 

Pharmacokinetic properties:  

Absorption  (Sitagliptin) : The absolute bioavailability of sitagliptin is approximately 87%. Metformin hydrochloride : The absolute bioavailability of a metformin hydrochloride 500-mg tablet given under fasting conditions is approximately 50-60%.

Distribution  Sitagliptin : The mean volume of distribution at steady state following a single 100-mg intravenous dose of sitagliptin to healthy subjects is approximately 198 liters. The fraction of sitagliptin reversibly bound to plasma proteins is low (38%). Metformin hydrochloride : The apparent volume of distribution (V/F) of metformin following single oral doses of metformin hydrochloride tablets 850 mg averaged 654 ± 358 L. Metformin is negligibly bound to plasma proteins, in contrast to sulfonylureas, which are more than 90% protein bound.

Metabolism Sitagliptin : Approximately 79% of sitagliptin is excreted unchanged in the urine with metabolism being a minor pathway of elimination. Approximately 16% of the radioactivity was excreted as metabolites of sitagliptin. Six metabolites were detected at trace levels and are not expected to contribute to the plasma DPP-4 inhibitory activity of sitagliptin. 

Metformin Hydrochloride : Intravenous single-dose studies in normal subjects demonstrate that metformin is excreted unchanged in the urine and does not undergo hepatic metabolism (no metabolites have been identified in humans) nor biliary excretion.  Excretion Sitagliptin : Approximately 100% of the administered radioactivity was eliminated in feces (13%) or urine (87%) within one week of dosing. The apparent terminal t1/2 following a 100-mg oral dose of sitagliptin was approximately 12.4 hours and renal clearance was approximately 350 mL/min. Metformin Hydrochloride: Renal clearance is approximately 3.5 times greater than creatinine clearance, which indicates that tubular secretion is the major route of metformin elimination. Following oral administration, approximately 90% of the absorbed drug is eliminated via the renal route within the first 24 hours, with a plasma elimination half-life of approximately 6.2 hours.

INDICATIONS : Type 2 Dabetes Mellitus to improve glycemic control.

DOSE : Twice daily with meals, with gradual dose escalation, to reduce the gastrointestinal (GI) side effects due to Metformin. 

CONTRAINDICATIONS Renal dysfunction, Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. History of a serious hypersensitivity reaction to  metfromin  or sitaliptin (one of the components of SITA M), such as anaphylaxis or angioedema. Temporarily discontinue SITA M in patients undergoing radiologic studies involving intravascular administration of iodinated contrast materials.  When used with an insulin secretagogue (e.g., sulfonylurea, 

ADVERSE DRUG REACTIONS  The most common adverse effects are diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, asthenia, and headache.