Sucosit

Sitagliptin belongs to a group of medicines called DPP-4 inhibitors. In people with type 2 diabetes, it is thought to work by slowing down the breakdown of incretin hormones. Because of this, Sitagliptin raises the levels of the active, intact hormones and keeps them working for longer.

The intestine releases incretin hormones, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), throughout the day. Their levels rise after a meal. The enzyme DPP-4 breaks these hormones down quickly. Incretins are part of the body's natural system for keeping blood glucose under control. When blood glucose is normal or high, GLP-1 and GIP stimulate the beta cells of the pancreas to make and release more insulin, using signalling pathways inside the cell that involve cyclic AMP. GLP-1 also reduces the amount of glucagon released by the alpha cells of the pancreas, which means the liver makes less glucose.

By keeping active incretin levels higher for longer, Sitagliptin increases insulin release and lowers glucagon in the blood. It does this only when glucose is raised, so the effect depends on blood glucose levels. Sitagliptin is selective for DPP-4. In laboratory studies, at concentrations close to those reached with therapeutic doses, it did not inhibit DPP-8 or DPP-9.

Sitagliptin has been studied in rats and rabbits, and it is placed in Pregnancy Category B. Animal studies don't always predict what happens in people, so sitagliptin should be used during pregnancy only when it is clearly needed.

In lactating rats, sitagliptin passes into the milk at a milk to plasma ratio of 4:1. We don't know whether it passes into human milk. Many drugs do, so care is needed when sitagliptin is given to a woman who is breastfeeding.

Pediatric use: the safety and effectiveness of Sitagliptin in patients under 18 years of age have not been established.

Geriatric use: the kidney clears a large part of Sitagliptin from the body, and elderly patients are more likely to have reduced renal function. So take care when choosing the dose in the elderly. It may be useful to check renal function before starting treatment and then at regular intervals.

Patients with mild renal insufciency (CrCl <50 ml/min or serum creatinine levels of <1.7 mg/DL in men and <1.5 mg/DL in women) need no dosage adjustment. In moderate renal insufciency (CrCl <30 to <50 mL/min, or serum creatinine levels of >1.7 to <3.0 mg/dL in men and >1.5 to <2.5 mg/dL in women), the dose is 50 mg once daily. Severe renal insufficiency (CrCl <30 mL/min or serum creatinine levels of >3.0 mg/dL in men and 2.5 mg/dL in women) and end-stage renal disease (ESRD) needing hemodialysis or peritoneal dialysis call for 25 mg once daily. Sitagliptin can be given regardless of hemodialysis.

In healthy volunteers during controlled clinical trials, single doses of Sitagliptin up to 800 mg were given. In one study, the 800 mg dose caused a maximal mean increase in QTc of 8.0 msec, and this effect is not considered clinically important. No clinical study has tested doses above 800 mg. In Phase I multiple-dose studies, Sitagliptin caused no dose-related clinical adverse reactions at doses of up to 600 mg per day for up to 10 days, or 400 mg per day for up to 28 days.

If an overdose happens, the usual supportive measures are reasonable. These include removing unabsorbed material from the gastrointestinal tract, clinical monitoring (including an electrocardiogram), and supportive therapy based on the patient's clinical status.

Sitagliptin is modestly dialyzable. In clinical studies, about 13.5% of the dose was removed during a 3 to 4 hour hemodialysis session. Prolonged hemodialysis may be considered if clinically appropriate. It is not known whether Sitagliptin can be removed by peritoneal dialysis.

Keep Sitagliptin below 25°C, in a dry place and away from light. Store the medicine somewhere safe, out of the reach of children. Don't use it after the expiry date. Sitagliptin should be dispensed only on the prescription of a registered physician.