Sitagliptin and Metformin Hydrochloride Tablets (II)

Chemical Composition and Strength:

This product is a compound preparation, containing Sitagliptin Phosphate and Metformin Hydrochloride as its active ingredients. Each tablet contains 50mg of sitagliptin phosphate (calculated as sitagliptin) and 850mg of metformin hydrochloride.

Indications

In combination with diet and exercise therapy, this product is indicated for patients with type 2 diabetes mellitus who have inadequate blood glucose control on metformin monotherapy or are already receiving combined therapy with both sitagliptin and metformin.

Dosage and Administration

When using this product for anti-hyperglycemic treatment, an individualized dosage should be administered based on the patient's current treatment regimen, the effectiveness of the treatment, and the patient's tolerance to the drug. However, the daily dosage should not exceed the maximum recommended dose of 100mg sitagliptin phosphate and 2000mg metformin.

The usual administration method is twice daily, taken with meals. When increasing the drug dosage, the dose should be increased gradually to reduce metformin-related gastrointestinal side effects.

Mechanism of Action:

This product is a compound preparation composed of sitagliptin and metformin.

• Sitagliptin Phosphate

Sitagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor. Incretins, including glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are released from the intestine throughout the day, with increased levels after meals. Incretins are part of the endogenous system involved in the physiological regulation of glucose homeostasis. When blood glucose concentrations are normal or elevated, GLP-1 and GIP can increase the synthesis and release of insulin from pancreatic β-cells through intracellular signaling pathways involving cyclic adenosine monophosphate (cAMP). In addition, GLP-1 can also inhibit the secretion of glucagon from pancreatic α-cells. The decrease in glucagon concentration and the increase in insulin level can reduce hepatic glucose production, thereby lowering blood glucose levels. The actions of GLP-1 and GIP are glucose-dependent. When blood glucose concentration is low, GLP-1 does not promote insulin release nor inhibit glucagon secretion. When glucose levels are higher than the normal concentration, the effect of GLP-1 and GIP on promoting insulin release is enhanced. In addition, GLP-1 does not impair the normal glucagon release response to hypoglycemia. The activity of GLP-1 and GIP is limited by the DPP-4 enzyme, which can rapidly hydrolyze incretins to produce inactive products. Sitagliptin can prevent the hydrolysis of incretins by DPP-4, thereby increasing the plasma concentrations of the active forms of GLP-1 and GIP. By increasing the levels of active incretins, sitagliptin can increase insulin release and decrease glucagon levels in a glucose-dependent manner.

• Metformin Hydrochloride

Metformin can improve glucose tolerance in patients with type 2 diabetes mellitus, and can reduce both fasting blood glucose and postprandial blood glucose. It can inhibit the gluconeogenesis of hepatic glycogen, reduce the absorption of glucose in the small intestine, and improve the sensitivity of peripheral tissues to insulin by increasing the uptake and utilization of glucose by peripheral tissues. Except for special circumstances, metformin generally does not cause hypoglycemia in patients with type 2 diabetes mellitus and normal individuals, nor does it lead to hyperinsulinemia. Although metformin treatment can reduce fasting insulin levels and the full-day insulin response, insulin secretion usually does not change.

Adverse Reactions

Adverse Reactions of Each Active Ingredient in Sitagliptin and Metformin Hydrochloride Compound Preparation

• Adverse Reactions Reported for Sitagliptin

In patients receiving sitagliptin monotherapy, the adverse event with an incidence of ≥5% and more common than in patients receiving placebo (regardless of the investigator’s assessment of causality) is nasopharyngitis.

• Adverse Reactions Reported for Metformin Hydrochloride

In patients treated with metformin, the reported adverse reactions with an incidence of >5% and more common than in patients receiving placebo (regardless of causality) are diarrhea, nausea/vomiting, flatulence, abdominal discomfort, dyspepsia, asthenia, and headache. Other less common adverse reactions include abnormal bowel movements, hypoglycemia, myalgia, dizziness, abnormal nails, rash, increased sweating, dysgeusia, chest discomfort, chills, influenza-like symptoms, hot flashes, palpitations, and weight loss. Metformin may reduce the absorption of vitamin B12, but it rarely causes anemia. Lactic acidosis caused by this product within the therapeutic dosage range is rare.

Contraindications

Since this product contains metformin, it is contraindicated in patients with severe renal impairment (eGFR < 45mL/min/1.73m²).

Known hypersensitivity to sitagliptin phosphate, metformin hydrochloride, or any other ingredients of this product.

Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma. For patients undergoing imaging examinations requiring intravascular injection of iodinated contrast media, the treatment with this product should be temporarily discontinued, as such contrast media may cause acute renal changes.