OHD<br />Dr. Khaled Dhaifullah Al-Harby<br />Consultant Family Medicine<br />
Sulfonylureas<br />Meglitinide Phenylalanine derivative (StarlixTM)<br />Alpha-glucosidase inhibitor  (acarbose)<br />Bigu...
Sulfonylureas (1st generation)<br />Agents:Tolbutamide (OrnaseTM) Tolazamide (TolinaseTM) Chlorpropamide (DiabeneseTM)<br ...
Sulfonylureas (1st generation)<br />Typical Dosage: <br />Tolbutamide: 0.25-2.0 g/day in divided doses; maximum, 3 g/day <...
Sulfonylureas (1st generation)<br />Precautions: Chlorpropamide remains active for up to 60 hours. Use extreme caution wit...
Sulfonylureas (2nd generation)<br />Agents:Glyburide = glibenclamide (MicronaseTM, DiabetaTM, GlynaseTM) glipizide (Glucot...
Sulfonylureas (2nd generation)<br />Typical dosing:<br />Glyburide: 1.25-2.50 mg/day twice a day; maximum 29 mg/day<br />G...
Sulfonylureas (2nd generation)<br />Precautions: Clearance may be diminished in patients with hepatic or renal impairment<...
Sulfonylureas<br />Blood Glucose Most Affected: Fasting and postprandial<br />SMBG Testing to Recommend: 2 - 3 times per d...
Meglitinide Phenylalanine derivative<br />Agents: Repaglinide (PrandinTM) , Nateglinide (StarlixTM)<br />Primary actions: ...
Meglitinide Phenylalanine derivative<br />Typical dosing: <br />Repaglinide (PrandinTM) New diagnosis or HbAlc &lt;8% 0.5 ...
Meglitinide Phenylalanine derivative<br />Precautions: Should not be used in patients with diabetic ketoacidosis and known...
Meglitinide Phenylalanine derivative<br />Blood Glucose Most Affected: Postprandial<br />SMBG Testing to Recommend: 2 hr a...
Biguanide<br />Agents : Metformin (GlucophageTM)<br />Primary action: Increases insulin sensitivity<br />Side effects: Nau...
Biguanide<br />Typical dosing:  500 mg/day twice a day with meals increase by 500 mg every 1-3 wk, twice or three times a ...
Biguanide<br />Precautions: Should not be used in patients who use alcohol frequently, liver, kidney disease or CHF becaus...
Biguanide<br />Blood Glucose Most Affected : Fasting<br />SMBG Testing to Recommend: Fasting<br />Greatest Risk for Hypogl...
Thiazolidinedione1-  Rosiglitazone (AvandiaTM)<br />Primary action: Increases insulin sensitivity<br />Side effects: Weigh...
Thiazolidinedione1-  Rosiglitazone (AvandiaTM)<br />Typical dosing: 4 mg/day in single or divided doses Increase to 8 mg/d...
Thiazolidinedione2-  Pioglitazone (ActosTM)<br />Primary action: Increases insulin sensitivity<br />Side effects: Weight g...
Thiazolidinedione2-  Pioglitazone (ActosTM)<br />Typical dosing: 15 or 30 mg/day; Maximum with or without food 45 mg for m...
Thiazolidinedione<br />Blood Glucose Most Affected: Fasting and postprandial<br />SMBG Testing to Recommend: 2 - 3 times p...
Alpha-glucosidase inhibitor <br />Agents : Acarbose (PrecoseTM) , Miglitol (GlysetTM) <br />Primary action: Blocks gut abs...
Alpha-glucosidase inhibitor <br />Typical dosing: 25 mg/day; increase by 25 mg/day every 4-6 wk; maximum, split dose befor...
Alpha-glucosidase inhibitor <br />Precautions: Avoid if serum creatinine is &gt;2.0 mg/dL.<br />Monitor serum transaminase...
Alpha-glucosidase inhibitor <br />Blood Glucose Most Affected: Postprandial<br />SMBG Testing to Recommend: 2 hr after mea...
Combinations <br />
glipizide and metforminGlucovanceTM   ,MetaglipTM<br />Primary action: Decreases hepatic glucose production and increases ...
GlucovanceTM<br />Typical dosing: Initial, 1.25 mg/250 mg once or twice a day with meals; increase every 2 wk by 1.25 mg/2...
GlucovanceTM<br />Precautions: Should not be used if frequent alcohol use, liver or kidney disease, or CHF is suspected<br...
GlucovanceTM<br />Blood Glucose Most Affected: Fasting and postprandial<br />SMBG Testing to Recommend: 2 - 3 times per da...
rosiglitazone and metforminAvandametTM<br />Primary action: Decreases hepatic glucose production, increases glucose uptake...
AvandametTM<br />Typical dosing: 1 mg/500 mg, 2 mg/500 mg or 4 mg/500 mg twice a day; dosage individualized based on curre...
Precautions: Should be avoided in patients with hepatic disease, CHF, renal disease<br />Comments: Agent is less expensive...
DAONIL® Tablets<br />COMPOSITION:Each tablet contains 5 mg glibenclamide.<br />
CONTRA-INDICATIONS:1- Hypersensitivity to sulphonylureas2- Diabetes mellitus in patients with a history of metabolic decom...
WARNING:<br />The administration of oral hypoglycaemic drugs has been reported to be associated with increased cardiovascu...
DOSAGE AND DIRECTIONS FOR USE:In general the initial dose is half a tablet (= 2,5 mg DAONIL® ) daily. The daily dose can t...
SIDE-EFFECTS : include skin rashes, photosensitivity, diarrhoea, nausea, vomiting, epigastric pain, feeling of gastric ful...
Interactions:<br />The hypoglycaemic effects may be enhanced by: propranolol and other beta-adrenergic blocking agents, su...
GLUCOPHAGE 500 mg TabletsGLUCOPHAGE 850 mg TabletsMetforminHydrochloride<br />PHARMACOLOGICAL ACTION:<br />Glucophage is a...
INDICATIONS:Non-insulin dependent diabetes when diet has failed and especially if the patient is overweight.<br />Glucopha...
CONTRA-INDICATIONS:Sensitivity to metformin hydrochloride. <br />Diabetic coma and ketoacidosis<br />impairment of renal f...
DOSAGE AND DIRECTIONS FOR USE:It is important that Glucophage tablets be taken in divided doses with meals.Adults:Initiall...
SIDE-EFFECTS :Gastro-intestinal adverse effects with anorexia, nausea and vomiting. <br />Metallic taste.<br />Lactic acid...
Glucophage is excreted by the kidney and regular monitoring of renal function is advised in all diabetics. <br />Glucophag...
Patients receiving continuous Glucophage therapy should have an annual estimation of Vitamin B12 levels because of reports...
Stabilisation of diabetic patients with Glucophage and insulin should be carried out in hospital because of the possibilit...
DIAMICRON®<br />COMPOSITION:Each tablet contains 80 mg of gliclazide.PHARMACOLOGICAL ACTION:Gliclazide stimulates the secr...
INDICATIONS:Therapy of maturity onset Diabetes Mellitus (non-insulin- dependent or Type II), where dietary management alon...
DOSAGE AND DIRECTIONS FOR USE:<br />generally between 1 tablet (80 mg) for mild cases, and 4 tablets (320 mg) daily for se...
SIDE-EFFECTS Weight changes - Most studies report no significant overall change in weight.Hypoglycaemic reactions may occu...
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brief on commonly prescribed oral hypoglycemic drugs (anti diabetic)

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  1. 1. OHD<br />Dr. Khaled Dhaifullah Al-Harby<br />Consultant Family Medicine<br />
  2. 2.
  3. 3. Sulfonylureas<br />Meglitinide Phenylalanine derivative (StarlixTM)<br />Alpha-glucosidase inhibitor (acarbose)<br />Biguanide (metformine)<br />Thiazolidinedione (avandia + actose)<br />
  4. 4. Sulfonylureas (1st generation)<br />Agents:Tolbutamide (OrnaseTM) Tolazamide (TolinaseTM) Chlorpropamide (DiabeneseTM)<br />Primary Action: Increases insulin production in pancreas<br />Side Effects: Hypoglycemia, weight gain, hyperinsulinemiaDisulfiram reaction with alcohol<br />Critical Tests: Metabolized in liver. Periodic evaluation of liver function tests<br />
  5. 5. Sulfonylureas (1st generation)<br />Typical Dosage: <br />Tolbutamide: 0.25-2.0 g/day in divided doses; maximum, 3 g/day <br />Tolazamide: 100-1,000 mg/day in divided doses; maximum, 1 g/day <br />Chlorpropamide: 100-500 mg/day twice a day; maximum, 750 mg/day<br />
  6. 6. Sulfonylureas (1st generation)<br />Precautions: Chlorpropamide remains active for up to 60 hours. Use extreme caution with elderly patients or patients with hepatic or renal impairment<br />Comments: Use of these agents is not recommended unless the patient has a well-established history of taking them. Second-generation sulfonylureas provide more predictable results with fewer side effects and more convenient dosing.<br />
  7. 7. Sulfonylureas (2nd generation)<br />Agents:Glyburide = glibenclamide (MicronaseTM, DiabetaTM, GlynaseTM) glipizide (Glucotrol, Glucotrol XLTM), glimepiride (AmarylTM)<br />Primary action: Increases insulin production in pancreas<br />Side effects: Hypoglycemia, weight gain, hyperinsulinemia<br />Critical tests: Metabolized in liver. Periodic evaluation of liver function tests<br />
  8. 8. Sulfonylureas (2nd generation)<br />Typical dosing:<br />Glyburide: 1.25-2.50 mg/day twice a day; maximum 29 mg/day<br />Glynase: 0.75-12.0 mg/day; maximum 20 mg/day <br />Glipizide: 2.5-20.0 mg/day twice a day; Maximum, 40 mg/day; or XL* 2.5-10.0 mg/day twice a day; maximum, 20 mg/day <br />Glimepiride: 1-8 mg/day; maximum, 8 mg/day<br />
  9. 9. Sulfonylureas (2nd generation)<br />Precautions: Clearance may be diminished in patients with hepatic or renal impairment<br />Comments: Glipizide is preferred with renal impairment. Doses &gt;15 mg should be split<br />
  10. 10. Sulfonylureas<br />Blood Glucose Most Affected: Fasting and postprandial<br />SMBG Testing to Recommend: 2 - 3 times per day, especially fasting<br />Greatest Risk for Hypoglycemia: 4 - 6 hr after meal and fasting<br />
  11. 11. Meglitinide Phenylalanine derivative<br />Agents: Repaglinide (PrandinTM) , Nateglinide (StarlixTM)<br />Primary actions: Increases insulin release from pancreas<br />Side effects: Hypoglycemia, weight gain, hyperinsulinemia<br />Clinical test: Metabolized in liver. Periodic evaluation of liver function tests.<br />
  12. 12. Meglitinide Phenylalanine derivative<br />Typical dosing: <br />Repaglinide (PrandinTM) New diagnosis or HbAlc &lt;8% 0.5 mg before meals 2-4 times a day HbA1c &gt;8: 1-2 mg, 15-30 min after each meal; increase weekly until results are obtained; maximum, 16 mg/day<br />Nateglinide (StarlixTM) 120, or 60 mg 3 times a day before meals<br />
  13. 13. Meglitinide Phenylalanine derivative<br />Precautions: Should not be used in patients with diabetic ketoacidosis and known hypersensitivity to drug or its inactive ingredients<br />Comments: Patients should be instructed to take medication ≤30 min before a meal. If meals are skipped or added, medication should be skipped or added as well<br />
  14. 14. Meglitinide Phenylalanine derivative<br />Blood Glucose Most Affected: Postprandial<br />SMBG Testing to Recommend: 2 hr after meal<br />Greatest Risk for Hypoglycemia: 2 - 3 hr after meal<br />
  15. 15. Biguanide<br />Agents : Metformin (GlucophageTM)<br />Primary action: Increases insulin sensitivity<br />Side effects: Nausea, diarrhea, metallic taste, very rare lactic acidosis<br />Critical tests: Contraindicated if serum creatinine is: &gt;1.5 mg/dL in men or &gt;1.4 mg/dL women, or use if creatinine clearance is abnormal. Monitor hematological and renal function annually<br />
  16. 16. Biguanide<br />Typical dosing: 500 mg/day twice a day with meals increase by 500 mg every 1-3 wk, twice or three times a day; usually most effective at 2,000 mg/day; maximum, 2,550 mg/day<br />
  17. 17. Biguanide<br />Precautions: Should not be used in patients who use alcohol frequently, liver, kidney disease or CHF because of risk of lactic acidosis.<br />Comments:Metformin is especially beneficial in obese patients due to potential for weight loss, improved lipid profile, and lack of potential for hypoglycemia requiring supplemental carbohydrate intake. Discontinue for 48 hr after procedure using contrast dye.<br />
  18. 18. Biguanide<br />Blood Glucose Most Affected : Fasting<br />SMBG Testing to Recommend: Fasting<br />Greatest Risk for Hypoglycemia : None if used as single agent<br />
  19. 19. Thiazolidinedione1- Rosiglitazone (AvandiaTM)<br />Primary action: Increases insulin sensitivity<br />Side effects: Weight gain, fluid retention, edema<br />Critical tests: Avoid initiation with patients with increased baseline liver enzyme levels (ALT &gt;2.5 times upper limit of normal). Liver enzymes monitored every 2 months for 12 months, then periodically. If ALT levels increase to &gt;3 times the upper limit of normal, discontinue use and recheck liver enzyme levels.<br />
  20. 20. Thiazolidinedione1- Rosiglitazone (AvandiaTM)<br />Typical dosing: 4 mg/day in single or divided doses Increase to 8 mg/day in 12 wk, if needed; maximum, 8 mg/day with or without food<br />Precautions: Should not be used in patients with CHF or hepatic disease.Can cause mild-to-moderate edema<br />Comments: Rosiglitazone is approved for use as monotherapy and in combination with metformin or sulfonylureas<br />
  21. 21. Thiazolidinedione2- Pioglitazone (ActosTM)<br />Primary action: Increases insulin sensitivity<br />Side effects: Weight gain, fluid retention, edema<br />Critical tests: Avoid initiation with patients who have liver disease or ALT levels &gt;2.5 times the upper limit of normal. Patients with mildly elevated liver enzymes (ALT levels 1-2.5 times the upper limit of normal) should be evaluated. Discontinue if &gt;3 times the upper limit of normal<br />
  22. 22. Thiazolidinedione2- Pioglitazone (ActosTM)<br />Typical dosing: 15 or 30 mg/day; Maximum with or without food 45 mg for monotherapy 30 mg for combination therapy<br />Precautions: Clearance may be diminished in patients with hepatic or renal impairment<br />Comments:Pioglitazone is approved for use as monotherapy or with metformin, sulfonylureas, or insulin<br />
  23. 23. Thiazolidinedione<br />Blood Glucose Most Affected: Fasting and postprandial<br />SMBG Testing to Recommend: 2 - 3 times per day, especially fasting<br />Greatest Risk for Hypoglycemia: After exercise when used with sulfonylureas or insulin<br />
  24. 24. Alpha-glucosidase inhibitor <br />Agents : Acarbose (PrecoseTM) , Miglitol (GlysetTM) <br />Primary action: Blocks gut absorption of complex sugars<br />Side effects: Gas and bloating, sometimes diarrhea for both drugs<br />Critical tests: Should not be used if GI disorders are concurrent.<br />
  25. 25. Alpha-glucosidase inhibitor <br />Typical dosing: 25 mg/day; increase by 25 mg/day every 4-6 wk; maximum, split dose before meals with first bite of food 300 mg/day (150 mg/day for weight&lt;60 kg)<br />
  26. 26. Alpha-glucosidase inhibitor <br />Precautions: Avoid if serum creatinine is &gt;2.0 mg/dL.<br />Monitor serum transaminase every 3 months for 1st year of therapy.<br />
  27. 27. Alpha-glucosidase inhibitor <br />Blood Glucose Most Affected: Postprandial<br />SMBG Testing to Recommend: 2 hr after meal<br />Greatest Risk for Hypoglycemia: None if used as single agent<br />
  28. 28. Combinations <br />
  29. 29. glipizide and metforminGlucovanceTM ,MetaglipTM<br />Primary action: Decreases hepatic glucose production and increases insulin secretion<br />Side effects: Possible hypoglycemia, nausea, diarrhea, abdominal pain for this combination drug<br />Critical tests: Contraindicated if serum creatinine is &gt;1.5 mg/dL in men or 1.4 mg/dL in women, or if creatinine clearance is abnormal. Monitor hematological and renal function annually<br />
  30. 30. GlucovanceTM<br />Typical dosing: Initial, 1.25 mg/250 mg once or twice a day with meals; increase every 2 wk by 1.25 mg/250 mg per day; 2nd line, 2.5mg/500 mg or 5 mg glyburide/500 mg twice a day with meals; maximum, 20 mg/2000 mg per day<br />
  31. 31. GlucovanceTM<br />Precautions: Should not be used if frequent alcohol use, liver or kidney disease, or CHF is suspected<br />Comments: May use 1.25mg/250mg and 2.5mg/500mg doses at different times of day for best glucose control. Incidence of hypoglycemia is higher for combination than for single agent use<br />
  32. 32. GlucovanceTM<br />Blood Glucose Most Affected: Fasting and postprandial<br />SMBG Testing to Recommend: 2 - 3 times per day, especially fasting<br />Greatest Risk for Hypoglycemia: 4 - 6 hr after meal and fasting<br />
  33. 33. rosiglitazone and metforminAvandametTM<br />Primary action: Decreases hepatic glucose production, increases glucose uptake, and decreases insulin resistance<br />Side effects: Diarrhea, edema, anemia for this combination drug<br />Critical tests: Contraindicated if serum creatinine is &gt;1.5 mg/dL in men or &gt;1.4 mg/dL in women, or if creatinin clearance is abnormal<br />
  34. 34. AvandametTM<br />Typical dosing: 1 mg/500 mg, 2 mg/500 mg or 4 mg/500 mg twice a day; dosage individualized based on current therapy. Maximum, 8 mg/2000mg per day<br />
  35. 35. Precautions: Should be avoided in patients with hepatic disease, CHF, renal disease<br />Comments: Agent is less expensive than its components separately. Decrease in GI upset is reported with metformin compared with rosiglitazone alone.<br />
  36. 36. DAONIL® Tablets<br />COMPOSITION:Each tablet contains 5 mg glibenclamide.<br />
  37. 37. CONTRA-INDICATIONS:1- Hypersensitivity to sulphonylureas2- Diabetes mellitus in patients with a history of metabolic decompensation e.g. acidosis, diabetic precoma and coma3- Diabetes mellitus complicated by fever trauma or gangrene and in patients with impaired renal or hepatic function or serious impairment of thyroid or adrenal function4- Insulin-dependent diabetes mellitus5- Diabetes mellitus in young people6- Pregnancy and lactation7- Hypersensitivity to glibenclamide<br />
  38. 38. WARNING:<br />The administration of oral hypoglycaemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin, although controversy exists concerning interpretation of these findings<br />
  39. 39. DOSAGE AND DIRECTIONS FOR USE:In general the initial dose is half a tablet (= 2,5 mg DAONIL® ) daily. The daily dose can then be raised gradually in steps of half a tablet. Raising the dose beyond 15 mg daily does not usually produce any increased response.In combination therapy with a biguanide, there may be a greater risk of cardiovascular mortality than with the use of glibenclamide alone.<br />
  40. 40. SIDE-EFFECTS : include skin rashes, photosensitivity, diarrhoea, nausea, vomiting, epigastric pain, feeling of gastric fullness, dizziness, headache, weakness, fever, hypoglycaemic reactions and paraesthesia.<br />Eosinophilia, cholestasis, hepatitis, jaundice, blood disorders including leucopenia, thrombocytopenia, aplasticanaemia, pancytopenia, haemolyticanaemia and agranulocytosis may occur. <br />The incidence of hypoglycaemia can be reduced if DAONIL® is taken with or immediately after a meal.<br />Transient visual disturbances may occur at the commencement of treatment.<br />When major surgery is to be performed, DAONIL® should be substituted with insulin therapy<br />
  41. 41. Interactions:<br />The hypoglycaemic effects may be enhanced by: propranolol and other beta-adrenergic blocking agents, sulphonamides, biguanides, ACE-inhibitors, fluoxetine, and tetracyclines.<br />The hypoglycaemic effect may be diminished by corticosteroids or diuretics, abuse of laxatives, and thyroid hormones. <br />Propranolol may inhibit normal physiological response to hypoglycaemia and mask the symptoms of hypoglycaemia<br />
  42. 42. GLUCOPHAGE 500 mg TabletsGLUCOPHAGE 850 mg TabletsMetforminHydrochloride<br />PHARMACOLOGICAL ACTION:<br />Glucophage is a biguanide oral anti-hyperglycaemic agent.<br /> Its mode of action is thought to be multifactorialand includes delayed uptake of glucose from the gastrointestinal tract, increased peripheral glucose utilisation mediated by increased insulin sensitivity, and inhibition of increased hepatic and renal gluconeogenesis. <br />No hypoglycaemia occurs when Glucophage is used alone but can occur when given concomitantly with a sulphonylurea, insulin or alcohol.<br />
  43. 43. INDICATIONS:Non-insulin dependent diabetes when diet has failed and especially if the patient is overweight.<br />Glucophage can be given alone as initial therapy, or can be administered in combination with a sulphonylurea. <br />In insulin-dependent diabetes: Glucophage may be given as an adjuvant to patients whose symptoms are poorly controlled.<br />
  44. 44. CONTRA-INDICATIONS:Sensitivity to metformin hydrochloride. <br />Diabetic coma and ketoacidosis<br />impairment of renal function<br />chronic liver disease<br />cardiac failure and recent myocardial infarction.<br />History of, or states associated with, lactic acidosis such as shock or pulmonary insufficiency<br />alcoholism (acute or chronic), and conditions associated with hypoxemia. <br />Pancreatitis. <br />The use of Glucophage during pregnancy is not advised. <br />There is no information available concerning the safety of Glucophage during lactation.<br />
  45. 45. DOSAGE AND DIRECTIONS FOR USE:It is important that Glucophage tablets be taken in divided doses with meals.Adults:Initially, one 850 mg tablet twice a day or one 500 mg tablet three times a day, with or after food.<br /> Good diabetic control may be achieved within a few days, but it is not usual for the full effect to be delayed for up to two weeks. <br />If control is incomplete a cautious increase in dosage to a maximum of 3 g daily is justified. <br />Once control has been obtained it may be possible to reduce the dosage of Glucophage.Children:Glucophage is not recommended for use.Elderly:Glucophage is indicated in the elderly, but not when renal function is impaired.<br />
  46. 46. SIDE-EFFECTS :Gastro-intestinal adverse effects with anorexia, nausea and vomiting. <br />Metallic taste.<br />Lactic acidosis has been associated with Glucophage but, has occurred to a greater extent in patients with contra-indications to therapy. <br />In patients with a metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonaemia) lactic acidosis should be suspected and Glucophage therapy stopped. <br />Lactic acidosis is a medical emergency which must be treated in hospital.<br />
  47. 47. Glucophage is excreted by the kidney and regular monitoring of renal function is advised in all diabetics. <br />Glucophage therapy should be stopped 2-3 days before surgeryand clinical investigations such as intravenous urography and intravenous angiography and reinstated only after control of renal function has been regained. <br />The use of Glucophage is not advised in conditions which may cause dehydration or in patients suffering from serious infections, trauma or on low calorie intake<br />
  48. 48. Patients receiving continuous Glucophage therapy should have an annual estimation of Vitamin B12 levels because of reports of decreased Vitamin B12 absorption.<br />
  49. 49. Stabilisation of diabetic patients with Glucophage and insulin should be carried out in hospital because of the possibility of hypoglycaemia until the correct ratio of the two drugs has been obtained.<br />Reduced renal clearance of Glucophage has been reported during cimetidine therapy, so a dose reduction should be considered. <br />
  50. 50. DIAMICRON®<br />COMPOSITION:Each tablet contains 80 mg of gliclazide.PHARMACOLOGICAL ACTION:Gliclazide stimulates the secretion of insulin by the beta cells of the pancreas.In addition to this pancreatic action, it has been demonstrated that gliclazide administration may improve the metabolic utilisationof glucose at a peripheral level.Gliclazide is well absorbed, and peak plasma concentrations occur (2-8) hours after administration. <br />The elimination half-life of gliclazide is 10-12 hours.<br />
  51. 51. INDICATIONS:Therapy of maturity onset Diabetes Mellitus (non-insulin- dependent or Type II), where dietary management alone has been insufficient.CONTRA-INDICATIONS:<br />Do not use in the presence of keto-acidosis or severe renal, hepatic, adrenal or thyroid dysfunction.<br />Do not use in patients with sulphonylurea intolerance.<br />Do not use in &quot;brittle&quot; or unstable diabetes.<br />Do not use in the first trimester of pregnancy, as safety in pregnancy has not been established.<br />Do not use in juvenile diabetes<br />
  52. 52. DOSAGE AND DIRECTIONS FOR USE:<br />generally between 1 tablet (80 mg) for mild cases, and 4 tablets (320 mg) daily for severe cases, taken in two divided doses preferably with meals.<br />In the majority of cases: 2 tablets per day with meals. 1 tablet with breakfast and 1 tablet with dinner.Diamicronmay be used in conjunction with insulin in insulin-dependent diabetes, but in that case, diabetic control should be checked by blood sugar readings, because of the possibility of hypoglycaemia. <br />In combined therapy with a biguanide there may be a greater risk of cardiovascular mortality than with the use of gliclazide alone<br />
  53. 53. SIDE-EFFECTS Weight changes - Most studies report no significant overall change in weight.Hypoglycaemic reactions may occur.<br />

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