Ccombination of Linagliptin, a DPP-4 inhibitor & Metformin, a member of the biguanide class) with complementary mechanisms of action to improve glycemic control in patients with type 2 diabetes mellitus.
Linagliptin: Linagliptin is an inhibitor of DPP-4, an enzyme that degrades the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP). Thus, Linagliptin increases the concentrations of active incretin hormones, stimulating the release of insulin in a glucose-dependent manner and decreasing the levels of glucagon in the circulation. Both incretin hormones are involved in the physiological regulation of glucose homeostasis. Incretin hormones are secreted at a low basal level throughout the day and levels rise immediately after meal intake. GLP-1 and GIP increase insulin biosynthesis and secretion from pancreatic beta cells in the presence of normal and elevated blood glucose levels. Furthermore, GLP-1 also reduces glucagon secretion from pancreatic alpha cells, resulting in a reduction in hepatic glucose output.
Metformin: Metformin lowers both basal and postprandial plasma glucose. It does not stimulate insulin secretion and therefore does not produce hypoglyceamia or increased weight gain. Metformin may exert its glucose-lowering effect via four mechanisms:
- by reduction of hepatic glucose production through inhibition of gluconeogenesis and glycogenolysis;
- in muscle, by modestly increasing insulin sensitivity, improving peripheral glucose uptake and utilization;
- by delaying intestinal glucose absorption;
- stimulate intracellular glycogen synthesis by acting on glycogen synthase and increase the transport capacity of glucose transporters (GLUT-1 & GLUT-4)
This is used for an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both linagliptin and metformin is appropriate.
|Generic||Linagliptin + Metformin|
|Therapeutic Class||Combination Oral hypoglycemic preparations|
|Manufacturer||Unimed Unihealth MFG, Ltd|
|Last Updated:||June 23, 2021 at 11:22 am|
Table Of contents
The dosage should be individualized on the basis of both effectiveness and tolerability. Maximum recommended dose of 2.5 mg Linagliptin and 1000 mg Metformin Hydrochloride twice daily with meals. Dose escalation should be gradual to reduce the gastrointestinal (GI) side effects associated with Metformin use.
Recommended starting dose: In patients currently not treated with Metformin, initiate treatment with 2.5 mg Linagliptin and 500 mg Metformin Hydrochloride twice daily. In patients already treated with Metformin, start with 2.5 mg Linagliptin and the current dose of Metformin Hydrochloride twice daily. Patients already treated with linagliptin and metformin, individual components may be switched to this combination containing the same doses of each component.
Most common side effects are nasopharyngitis and diarrhea. Hypoglycemia is more common in patients treated with this combination and sulfonylureas.
In a patient with lactic acidosis who is taking Metformin, the drug should be discontinued immediately and supportive therapy promptly instituted. There have been postmarketing reports of acute pancreatitis. If pancreatitis is suspected, promptly discontinue Linagliptin & Metformin. Temporarily discontinue Linagliptin & Metformin in patients undergoing radiologic studies with intravascular administration of iodinated contrast materials or any surgical procedures necessitating restricted intake of food and fluids. Metformin may lower Vitamin B12 levels; so hematologic parameters shoud be monitored annually.
Cationic drugs (amiloride, digoxin, morphine, ranitidine, trimethoprim etc.): May reduce metformin elimination. P-glycoprotien/CYP3A4 inducer (i.e. rifampin): The efficacy of this medicine may be reduced when administered in combination.
Pregnancy & Breastfeeding use
Pregnancy category B. There are no adequate and well-controlled studies in pregnant women with this combination or its individual component; so it should be used during pregnancy only if clearly needed. Caution should also be excercised when it is administered to a lactating mother.
Although Linagliptin undergoes minimal renal excretion, Metformin is known to be substantially excreted by the kidney. The risk of Metformin accumulation and lactic acidosis increases with the degree of renal impairment. Therefore, this combination is contraindicated in patients with renal impairment. It is also contraindicated in acute or chronic metabolic acidosis (diabetic ketoacidosis) and in hypersensitivity to Linagliptin or Metformin.
Pediatric Use: Safety and effectiveness of Linagliptin & Metformin combination in pediatric patients under 18 years of age have not been established.
Geriatric Use: Linagliptin is minimally excreted by the kidney; however, Metformin is substantially excreted by the kidney. Considering that aging can be associated with reduced renal function, Linagliptin & Metformin combination should be used with caution as age increases.
Renal Impairment: Studies characterizing the pharmacokinetics of Linagliptin and Metformin after administration of Linagliptin & Metformin combination in renally impaired patients have not been performed. Since Metformin is contraindicated in patients with renal impairment, use of Linagliptin & Metformin combination is also contraindicated in patients with renal impairment (e.g., serum creatinine >=1.5 mg/dL [males] or >=1.4 mg/dL [females], or abnormal creatinine clearance).
Hepatic Impairment: Studies characterizing the pharmacokinetics of Linagliptin and Metformin after administration of Linagliptin & Metformin combination in hepatically impaired patients have not been performed. However, use of Metformin alone in patients with hepatic impairment has been associated with some cases of lactic acidosis. Therefore, use of Linagliptin & Metformin combination is not recommended in patients with hepatic impairment.
Keep in a dry place away from light and heat. Keep out of the reach of children.