Mechanism of Action
JANUVIA targets 2 core defects of diabetes in a glucose-dependent manner
JANUVIA + metformin targets 3 core defects of diabetes
- • Metformin increases glucose uptake and
- utilization (greater in the liver than in muscle
- and fat)1,2
- • JANUVIA works in a glucose-dependent manner
- to enhance active incretin levels, which stimulate
- the synthesis and release of insulin from beta
- • Metformin reduces glucose production in the liver (gluconeogenesis) and diminishes the
- breakdown of glycogen into glucose (glycogenolysis)2,3
- • JANUVIA improves the ability of alpha cells to suppress glucagon secretion (by
- enhancing active incretin levels), which results in reduced glycogen breakdown and glucose synthesis
- • JANUVIA increases insulin synthesis and release from pancreatic beta cells, which
- helps reduce hepatic glucose overproduction
Glucose-dependent mechanism: targets insufficient insulin release and hepatic glucose overproduction
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Selected Important Risk Information
When JANUVIA was used in combination with a sulfonylurea or insulin, medications known to cause hypoglycemia, the incidence of hypoglycemia was increased over that of placebo. Therefore, a lower dose of sulfonylurea or insulin may be required to reduce the risk of hypoglycemia.
The incidence (and rate) of hypoglycemia based on all reports of symptomatic hypoglycemia were: 12.2% (0.59 episodes/patient–year) for JANUVIA 100 mg in combination with glimepiride (with or without metformin), 1.8% (0.24 episodes/patient–year) for placebo in combination with glimepiride (with or without metformin), 15.5% (1.06 episodes/patient-year) for JANUVIA 100 mg in combination with insulin (with or without metformin), and 7.8% (0.51 episodes/patient-year) for placebo in combination with insulin (with or without metformin).
JANUVIA® (sitagliptin) tablets is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
JANUVIA has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk of developing pancreatitis while taking JANUVIA.
References: 1. Bailey CJ, Turner RC. Metformin. N Engl J Med. 1996;334(9):574–579. 2. Kirpichnikov D, McFarlane SI, Sowers JR. Metformin: an update. Ann Intern Med. 2002;137(1):25–33. 3. Krentz AJ, Bailey CJ. Oral antidiabetic agents: current role in type 2 diabetes mellitus. Drugs. 2005;65(3):385–411.
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