Weiyitong Saxagliptin and Metformin Hydrochloride Sustained‑release Tablets (Ⅰ)

1. Indications and Usage
Glycemic Control: Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already treated with a combination of saxagliptin and metformin or whose diabetes is inadequately controlled on metformin alone.
Limitations of Use: This medication is not for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis. It has not been studied in patients with a history of pancreatitis.
2. Dosage and Administration
Starting Dose: The dose should be individualized based on the patient’s current regimen, efficacy, and tolerability. For patients inadequately controlled on metformin, the recommended starting dose is 5 mg saxagliptin/500 mg metformin once daily.
Administration: The tablet should be taken once daily with the evening meal to reduce gastrointestinal side effects associated with metformin.
Tablet Handling: The tablet must be swallowed whole. It must not be crushed, split, or chewed, as this would destroy the sustained-release mechanism.
Maximum Dose: The maximum recommended daily dose is 5 mg saxagliptin and 2000 mg metformin.
3. Mechanism of Action
Saxagliptin: A dipeptidyl peptidase-4 (DPP-4) inhibitor that increases the levels of active incretins (GLP-1 and GIP). This enhances glucose-dependent insulin secretion and suppresses glucagon release from the liver.
Metformin Hydrochloride: A biguanide that decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization.
4. Safety and Warnings
Lactic Acidosis: A rare but serious and potentially fatal complication associated with metformin accumulation. Risk factors include renal impairment, sepsis, dehydration, excessive alcohol intake, and hepatic impairment. If suspected, the drug must be discontinued immediately and the patient hospitalized.
Pancreatitis: Post-marketing reports of acute pancreatitis have been reported with DPP-4 inhibitors. Patients should be monitored for symptoms such as persistent severe abdominal pain. If pancreatitis is suspected, the medication should be discontinued promptly.
Renal Impairment: Renal function must be assessed prior to initiation and periodically thereafter. The drug is contraindicated in patients with an eGFR below 30 mL/min/1.73 m².
Hypoglycemia: The risk of hypoglycemia increases when this combination is used concomitantly with insulin or insulin secretagogues (e.g., sulfonylureas). A lower dose of the insulin secretagogue or insulin may be required.
5. Adverse Reactions and Clinical Research
Common Adverse Reactions: Gastrointestinal symptoms (such as diarrhea, nausea, and vomiting) are the most common adverse reactions associated with metformin. Upper respiratory tract infections and headaches are also frequently reported.
Other Adverse Effects: Hypoglycemia (especially when combined with sulfonylureas or insulin), vitamin B12 deficiency with long-term use, and hypersensitivity reactions (e.g., rash, angioedema).
Clinical Findings: Clinical trials have demonstrated significant reductions in HbA1c compared to monotherapy, with a safety profile consistent with the individual components.
6. Drug Interactions
Strong CYP3A4/5 Inhibitors: Concomitant use with strong CYP3A4/5 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir) increases saxagliptin exposure. The dose of saxagliptin should be limited to 2.5 mg once daily.
Insulin and Sulfonylureas: Concurrent use may significantly increase the risk of hypoglycemia, requiring dose adjustments.
Alcohol: Intake should be limited or avoided due to the increased risk of lactic acidosis.
Iodinated Contrast Media: The drug should be temporarily discontinued at the time of or prior to imaging procedures involving iodinated contrast in patients with reduced renal function or other risk factors.
7. Pharmaceutical Information
Active Ingredients: Saxagliptin and Metformin Hydrochloride.
Strengths: Type Ⅰ is commonly available as 5 mg saxagliptin/1000 mg metformin sustained-release tablets.
Appearance: Film-coated sustained-release tablets, typically pink or white to off-white.
Storage: Store at controlled room temperature (below 30°C) in a dry place, protected from light and moisture.