Brand Name: MODULIN-M
Generic Name: Linagliptin 2.5 mg + Metformin 500/800/SR 1000 mg
Preparation: Tablets
Pharmacological Category: Antidiabetic

Mechanism of Action (MOA)
Linagliptin is a competitive, reversible DPP-4 inhibitor. Inhibition of this enzyme slows the breakdown of glucagon-like peptide 1 (GLP-1) and glucose-dependant insulinotropic polypeptide (GIP). GLP-1 and GIP stimulate the release of insulin from beta cells in the pancreas while inhibiting release of glucagon from pancreatic apha cells. These effects together reduce the breakdown of glycogen in the liver and increase insulin release in response to glucose.

Metformin decreases blood glucose levels by decreasing hepatic glucose production, decreasing intestinal absorption of glucose and improving insulin sensitivity by increasing peripheral glucose uptake and utilization. These effects are mediated by the initial activation of AMP-activated protein kinase (AMPK), a liver enzyme that plays an important role in insulin signaling, whole body energy balance, and the metabolism of glucose and fats.

• Absorption: Absorbed from gastrointestinal tract
• Bioavailability: 30%
• Peak Plasma Time: 1.5 hours
• Distribution: Extensive
• Protein Binding: 75-99%
• Metabolism: Not extensively metabolized
• Elimination Half-life: About 12 hours
• Excretion: Faeces unchaged (80%), urine unchanged (5%)
• Absorption: Slowly and incompletely absorbed from the gastrointestinal tract
• Bioavailability: About 50 to 60%
• Plasma Half-life: 2 to 6 hours
• Protein Binding: Negligible
• Metabolism: Does not undergo metabolism
• Elimination Half-life: 4 to 9 hours
• Excretion: Urine (unchanged drug)

Indication and Dosage
Type II Diabetes mellitus: 1 tablet twice daily as an adjunct to diet and exercise
Maximum dose: Linagliptin 5 mg + Metformin 1000 mg daily

Side Effects
COMMON: Hypoglycemia, increased serum lipase, nasopharyngitis, hyperuricemia, cough, anorexia, nausea, vomiting, diarrhoea, taste disturbance, weight loss, and impaired vitamin B12 absorption
FREQUENCY NOT DEFINED: Urticaria, myalgia, and asthma
REPORTED: Acute pancreatitis, anaphylaxis, angioedema, bullous pemphigoid, exfoliation of skin, oral mucosa ulcer, severe arthralgia, severe hypersensitivity, skin rash, and stomatitis
RARE: Skin rashes, hypoglycemia

• Hypersensitivity
• type 1 diabetes mellitus or diabetic ketoacidosis
• renal disease or dysfunction (serum creatinine level 1.5 mg per dL or above in male, 1.4 mg per dL or above in female or abnormal creatinine clearance) which may result from cardiovascular collapse (shock), acute myocardial infarction and septicemia
• patients undergoing radiologic studies

Warnings/ Precautions
• Should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.
• There is risk of developing acute pancreatitis.
• Bullous pemphigoid has been observed in patients taking linagliptin.
• Metformin should not be given to patients with even mild renal impairment as metformin may predispose patients to lactic acidosis and renal function should be monitored throughout the therapy. Conditions associated with hypoxia, such as acute heart failure, recent myocardial infarction, or shock may increase the risk of lactic acidosis. Other conditions that may also predispose to lactic acidosis in a patient taking a biguanide include excessive alcohol intake and hepatic impairment.
• Metformin should be temporarily stopped for examinations using contrast media.
• Annual monitoring of vitamin B12 concentration is advised during long term treatment.

Drug Interactions
• Thiazide and thiazide-like diuretics may diminish the therapeutic effect of linagliptin.
• Linagliptin enhances hypoglycemic effect of sulphonylureas.
• Salicylaytes may enhance the hypoglycemic effect of linagliptin.
• Ritonavir increases concentration of linagliptin.
• Quinolone may enhance the hypoglycemic effect of linagliptin.
• Alcohol may increase the risk of lactic acidosis as well as of hypoglycemia.
• Metformin diminishes phenprocaumon activity.
• With didanosine, stavudine and tenofovir fatal lactic acidosis has been reported.
• Cimetidine increases plasma metformin concentration.

Pregnancy Category: B; however it is preferable to avoid the use of linagliptin during pregnancy

MODULIN-M 500 : 5 X 2 X 15’s
MODULIN-M 850 : 5 X 2 X 15’s
MODULIN-M SR 1000: 5 X 2 X 15’s