Sitagil M ER100 mg+1000 mg

Established Use

Sitagil M ER is indicated, together with diet and exercise, to improve blood sugar (glycemic) control in adults with type 2 diabetes mellitus. Sitagil M ER may be used:

• As initial combination therapy in adults who need both a DPP-4 inhibitor and metformin to reach their blood sugar targets.
• As add-on therapy in adults whose type 2 diabetes is not adequately controlled on metformin alone, on sitagliptin alone, or on metformin combined with a sulfonylurea or insulin, when treatment with both components is appropriate.

Limitations of Use

• Sitagil M ER is not indicated for type 1 diabetes mellitus or for the treatment of diabetic ketoacidosis.
• Sitagil M ER has not been studied in patients with a history of pancreatitis, and Sitagil M ER is not a substitute for diet and exercise, which should be continued throughout treatment.

Sitagliptin

After oral dosing, sitagliptin is well absorbed, with peak blood levels reached within 1 to 4 hours and an absolute bioavailability of about 87%; food does not meaningfully affect its absorption. It distributes throughout the body with moderate plasma protein binding (about 38%). Only a small portion (about 16%) is metabolized in the liver, mainly involving the enzyme CYP3A4; the majority (about 79%) is eliminated unchanged by the kidneys, with a terminal half-life of roughly 12 hours. Because it is cleared mainly by the kidneys, blood levels of sitagliptin rise substantially in people with reduced kidney function.

Metformin

Metformin is absorbed more slowly and incompletely, with an absolute bioavailability of roughly 50-60% under fasting conditions; food modestly reduces and delays its absorption. It is not significantly bound to plasma proteins and does not undergo liver metabolism - it is eliminated essentially unchanged by the kidneys, mainly through active tubular secretion, with a plasma half-life of around 6 hours. Because metformin depends on the kidneys for clearance, kidney function is a key factor in determining safe dosing.

• Take Sitagil M ER with meals (usually with breakfast and dinner) to help reduce stomach upset such as nausea or diarrhea.
• Swallow the tablet whole with a glass of water; do not crush, split, or chew the tablet, especially for extended-release formulations.
• Take Sitagil M ER at the same times every day to maintain steady blood sugar control.
• Do not skip meals after taking a dose, since this can increase the risk of low blood sugar (hypoglycemia), especially if also taking insulin or a sulfonylurea.
• If a dose is missed, take it as soon as remembered unless it is almost time for the next dose - in that case, skip the missed dose and continue the regular schedule; do not take a double dose.
• Continue following the recommended diet and exercise plan alongside Sitagil M ER, as lifestyle measures remain an essential part of treatment.
• Attend all scheduled blood sugar, HbA1c, and kidney function tests, as these guide dose adjustments.

• Iodinated contrast media: increases the risk of acute kidney injury and metformin-associated lactic acidosis; Sitagil M ER is temporarily discontinued around imaging procedures (see Precautions and Warnings).
• Alcohol: potentiates the effect of the metformin component on lactate metabolism, increasing lactic acidosis risk; avoid excessive intake.
• Carbonic anhydrase inhibitors (e.g., topiramate, zonisamide, acetazolamide): may increase the risk of lactic acidosis; use with caution and monitor closely.
• Drugs that reduce metformin renal clearance (e.g., ranolazine, vandetanib, dolutegravir, cimetidine): can raise metformin plasma levels, increasing lactic acidosis risk.
• Insulin and insulin secretagogues (e.g., sulfonylureas): combined use increases hypoglycemia risk; dose adjustment of these agents may be needed.
• Drugs that affect glycemic control (e.g., corticosteroids, thiazide diuretics, certain thyroid medicines): may reduce the glucose-lowering effect of Sitagil M ER and lead to loss of control; monitor blood sugar more closely.

Common Side Effects

Diarrhea, nausea/vomiting, flatulence, abdominal discomfort, indigestion, headache, and upper respiratory tract infection are commonly reported. Low blood sugar (hypoglycemia) can occur, particularly when Sitagil M ER is combined with insulin or a sulfonylurea.

Serious Side Effects - Seek Medical Attention

• Signs of lactic acidosis - unusual muscle pain, difficulty breathing, unusual sleepiness, abdominal pain with nausea or vomiting, feeling cold, dizziness, or a slow or irregular heartbeat (see Precautions and Warnings).
• Signs of acute pancreatitis - severe, persistent abdominal pain, sometimes spreading to the back, with or without vomiting.
• Serious allergic reactions - swelling of the face, lips, tongue, or throat, difficulty breathing or swallowing, or severe skin reactions such as blistering (Stevens-Johnson syndrome or bullous pemphigoid).
• Signs of heart failure - unusual shortness of breath, rapid weight gain, or swelling in the ankles or legs.
• Reduced kidney function.
• Symptoms of vitamin B12 deficiency with long-term use - unusual tiredness, weakness, or tingling in the hands or feet.
• Severe or persistent joint pain.

Pregnancy

There are no adequate and well-controlled studies of Sitagil M ER in pregnant women. Poorly controlled diabetes during pregnancy increases the risk of complications for both mother and baby, including a higher background risk of major birth defects and miscarriage compared with a pregnancy without diabetes. Limited published data on the metformin component have not shown a clear increase in major birth defects or miscarriage risk, and animal studies with both components have not shown harm at doses relevant to human use, but human data on the combination itself remain limited. Sitagil M ER should be used during pregnancy only if a doctor decides the benefit clearly outweighs the risk, with good blood sugar control maintained throughout pregnancy under close medical supervision.

Breastfeeding

Metformin passes into breast milk in small amounts, generally reported at less than 1% of the mother's weight-adjusted dose, and available data have not shown adverse effects in breastfed infants. Whether sitagliptin passes into human breast milk is not well established, although it has been detected in the milk of lactating animals. Because of this limited data on the combination, a doctor should be consulted to weigh the benefits of breastfeeding against the mother's need for Sitagil M ER, and the breastfed infant should be monitored for any unusual symptoms.

• Lactic acidosis (rare but serious): the metformin component can rarely cause lactic acidosis, a medical emergency, more likely in patients with renal impairment, hepatic impairment, dehydration, excessive alcohol use, acute heart failure, sepsis, or advanced age; discontinue Sitagil M ER promptly and seek emergency care if symptoms (unusual muscle pain, breathing difficulty, abdominal pain, feeling cold, dizziness, or a slow or irregular heart rate) develop.
• Renal function monitoring: kidney function should be assessed before starting and periodically during treatment, as dosing depends on eGFR and reduced kidney function raises the risk of drug accumulation and lactic acidosis (see Dosage).
• Use around iodinated contrast imaging: temporarily stop Sitagil M ER at or before contrast procedures in at-risk patients and restart only after renal function is confirmed stable (see Interaction).
• Risk of acute pancreatitis: rare postmarketing reports of pancreatitis, including severe forms, have occurred with sitagliptin-containing products; stop treatment promptly if persistent severe abdominal pain occurs.
• Hypersensitivity reactions: rare but serious allergic reactions (anaphylaxis, angioedema, Stevens-Johnson syndrome) have been reported with sitagliptin, usually within the first 3 months of treatment; discontinue and seek care if signs appear.
• Heart failure: monitor for signs and symptoms of heart failure (swelling, sudden weight gain, breathlessness), particularly in those with existing heart or kidney disease.
• Vitamin B12 deficiency: long-term metformin use may reduce vitamin B12 levels; periodic monitoring is recommended, especially in those with anemia or peripheral neuropathy.
• Hypoglycemia with combination therapy: risk increases when Sitagil M ER is used with insulin or sulfonylureas; dose adjustment of those agents may be required.
• Hepatic impairment: use is not recommended due to increased lactic acidosis risk from reduced lactate clearance.
• Severe joint pain and skin reactions: rare reports of severe arthralgia and bullous pemphigoid have occurred with DPP-4 inhibitors; discontinue if suspected and seek medical advice.
• Alcohol: avoid excessive alcohol intake, which increases lactic acidosis risk.

Children

Safety and effectiveness of Sitagil M ER have not been established in children, and Sitagil M ER is not recommended for pediatric use (see Pediatric Uses).

Elderly

Older adults, especially those aged 65 and above, may be more likely to have reduced kidney, liver, or heart function, and are at higher risk of lactic acidosis. Treatment with Sitagil M ER is usually started at the lower end of the dosing range, with more frequent monitoring of kidney function.

Renal (Kidney) Impairment

Dosing of Sitagil M ER depends on kidney function. Sitagil M ER is contraindicated in severe renal impairment (eGFR below 30 mL/min/1.73 m²) and generally not recommended for starting treatment when eGFR is between 30 and 45 mL/min/1.73 m² (see Dosage and Precautions and Warnings).

Hepatic (Liver) Impairment

Use of Sitagil M ER is not recommended in patients with hepatic impairment, because reduced ability to clear lactate can increase the risk of lactic acidosis (see Precautions and Warnings).

Other Populations

Patients undergoing surgery, those who are seriously ill, dehydrated, or with conditions that reduce tissue oxygen supply (such as acute heart failure or a recent heart attack) require careful assessment, as these situations raise the risk of lactic acidosis and may require temporary discontinuation of Sitagil M ER.

Sitagliptin

Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor. It slows the breakdown of incretin hormones (such as GLP-1 and GIP) released by the gut after meals. By raising the active levels of these hormones, sitagliptin increases insulin release from the pancreas and reduces glucagon release from the liver, both in a glucose-dependent manner, helping to lower blood sugar after meals and overall.

Metformin

Metformin belongs to the biguanide class. It lowers blood sugar mainly by reducing glucose production by the liver, decreasing the amount of sugar absorbed from the intestine, and improving the sensitivity of muscle and fat tissue to insulin, which increases the uptake and use of glucose by the body.