- Diformin® is a medicine which contains two components: Metformin
  Hydrochloride and Glimepiride. 
- Metformin Hydrochloride is an oral antidiabetic (biguanide) agent. Its
  mechanism of action is differs from those of sulfonylurea, where it decreases 
  hepatic glucose production, decreases intestinal absorption of glucose and 
  improves insulin sensitivity (increase peripheral glucose uptake and utilization). 
  It doesn’t produce hypoglycemia and doesn’t change insulin secretion. 
- Glimepiride is a sulfonylurea hypoglycemic agent and act by stimulation of 
  insulin release from functioning pancreatic beta cells and increases sensitivity of 
  peripheral tissues to insulin.
- Absorption: Metformin hydrochloride is slowly and incompletely absorbed 
  from the gastrointestinal tract, inverse Glimepiride where it completely 
  absorbed from the gastrointestinal tract. The peak plasma concentrations for 
  both occur between 2- 3 hours, and bioavailability from 50- 60% for 
- Plasma protein binding: Metformin’s plasma protein binding is negligible, and 
  it excreted unchanged in urine, where the plasma elimination half life range 
  from about 2 -6 hours. 
  Glimepiride is highly bound to plasma proteins and is completely metabolized.   
  The half life after multiple doses is about 9 hours and ( 60%) of  dose is 
  eliminated in the urine and 40% in the feces.

- Each film coated tablet of Diformin®  500/ 4 contains :  
- Metformin Hydrochloride    500  mg
- Glimepiride                             4   mg
- Each film coated tablet of Diformin® 500/ 2 contains :       
- Metformin Hydrochloride    500  mg
- Glimepiride                        2   mg

*Diformin® is contraindicated in the following cases:- 
- Insulin dependent diabetes (Type 1- diabetes requiring lnsulin therapy).
- Diabetic ketoacidosis. 
- Hypersensitivity to Diformin®, or any of its ingredients,and other Sulfonylureas  
  and biguanides. 
- Lactic acidosis. 
- Renal diseases or renal dysfunction.
- Heart failure.
- Recently heart attack, severe circulatory  problems or breathing difficulty.
- Liver diseases.
- Severe infections or any dehydration.
- X-ray with iodinated contrast materials administered IV stop taking Diformin® 
  at the time of and for a few days after this procedure.
- If you are not eating sufficiently, if you are debilitated or suffering from pituitary 
  or adrenal insufficiency.

- Diformin® hypoglycemic effects may potentiated when administered with the 
  following drugs: insulin and other oral antidiabetics, ACE inhibitors, allopurinol, 
  anabolic steroids and male sex hormones, chloramphenicol, coumarin derivatives, 
  cyclophosphamide, disopyramide, fenfluramine, fenyramidol, fibrates, fluoxetine, 
  guanethidine, ifosfamide, MAO inhibitors, miconazole, para- aminosalicylic acid, 
  pentoxifylline(high injection dose), phenylbutazone, azapropazone, 
  oxyphenbutazone, probenecide, quinolines, salicylates, sulfinpurazone, 
  sulfonamides, tetracyclines, tritoqualine, and trofosfamide. 
- Weaking of blood sugar lowering effect and thus raised blood sugar levels may 
  occur when the following medicines is taken, for example: 
  Acetazolamide, barbiturates, corticosteroides, diazoxide, diuretics, epinephrine, 
  and other sympathomimetic agents, glocagon, laxatives, nicotinic acid, estrogens 
  and progestogens, phenothiazines, phenytion, rifampicin and thyroid hormones, 
- H2 receptor antagonists, clonidine and reserpine may potentiate or decrease the 
  Diformin® effects. 
- Beta- blockers decrease glucose tolerance. In patients with diabetes melitus this 
  may lead to deterioration of metabolic control, in addition, beta blockers may  
  potentiate or weaken the blood sugar lowering action of Diformin® unpredictably.
- coumarin derivatives may increase or decrease the activity of Diformin®.
- Lactic acidosis may occur by concomitant. with Diformin® administration of the 
  following drugs : Iodinated contrast materials and antibiotics having strong renal 
  toxicity (for example gentamycin).

- Diformin® should not be used during pregnancy, if there is planning for 
  pregnancy or breast feeding. 

- Hypoglycemia.
- Lactic acidosis practically in those who have renal dysfunction.
- Temporary visual impairment may occur due to change in blood sugar levels.
- Occasionally, gastrointestinal symptoms may occur, most frequently during 
  initiation of therapy and resolve spontaneously in most cases: Nausea, vomiting, 
  sensation of pressure or fullness in the epigastria, flatulence, abdominal pain, 
  and diarrhea. In rare cases, liver enzyme levels may increase. 
- Severe changes in blood picture may occur, rarely, thrombopenia and in isolated 
  cases, leucopenia, hemolytic anemia, erythrocytopenia and agranulocytosis, and 
  pancytopenia may develop.
- A decrease in vit B12 levels can be observed, therefore, serum B12 levels 
  should be appropriately monitored.
- Allergic or pseudoallergic reactions may occur e.g.:(in the form of itching, 
  urticaria or rashes), such reactions may be mild, but may become more serious 
  and may be complained by dyspnoea, and fall in blood pressure, sometimes  
  progressing to shock. in case of urticaria you should tell the doctor In rare cases, 
  a decrease in serum sodium, inflammation of blood vessels and hypersensitivity 
  of the skin to light may occur. 

Over dosage:-
 If an excessive dose is taken, this may lead to severe and sometimes 
 life-threatening hypoglycemia and may require hospitalization even as 
 precautionary  measure. 

- Please follow closely the instructions for dosage monitoring (blood and urine 
  tests), diet and physical activity ( physical work and exercise) as discussed with 
  your doctor. 
- Inform your doctor in event of the following: surgery, fever, infection, difficulty in 
- The risk of hypoglacemia is increased in the first weeks of treatment so you need a 
  strict monitoring during them.  
- Vision, alertness and reactions during driving or machine operation may be 
  impaired during treatment due to that diabetes is not properly balanced or in the 
  case of hypoglycemia.

- Blister contains 10 tablets, pack contains three blisters.

- Store in a dry place, away from moisture at a temperature below 25 °C.