ADVANTAGESADVANTAGES• Reduces Reduces insulin resistanceinsulin resistance..• High initial High initial responseresponse rate. rate.• Long record of relative Long record of relative safety.safety.• No No weightweight gain or modest weight loss. gain or modest weight loss.
TZD/pioglitazone: TZD/pioglitazone: Mechanism of actionMechanism of action
• Pioglitazone increases glucose uptake in Pioglitazone increases glucose uptake in skeletal muscle and adipose tissue –skeletal muscle and adipose tissue –increasing increasing glycolysis glycolysis + synthesis of + synthesis of glycogen glycogen in skeletal muscle.in skeletal muscle.
• Increase Increase oxidationoxidation and lipogenesis in adipose and lipogenesis in adipose tissue – increase peripheral glucose tissue – increase peripheral glucose sensitivity and utilization.sensitivity and utilization.
Side effectsSide effects• Upper Respiratory Tract infection.Upper Respiratory Tract infection.• Weight gain.Weight gain.• Anemia - Hb and Hematocrit.Anemia - Hb and Hematocrit.• Haemodulation and Oedema.Haemodulation and Oedema.• Plasma volume expansion and cardiac Plasma volume expansion and cardiac
hypertrophy.hypertrophy.• Ovulation and possible pregnancy.Ovulation and possible pregnancy.• Unknown long term safety profile.Unknown long term safety profile.
ADVANTAGESADVANTAGES• Corrects a primary pathophysiologic Corrects a primary pathophysiologic
impairment: insulin resistance.impairment: insulin resistance.• Once daily dosing.Once daily dosing.• Lowers serum triglycerides.Lowers serum triglycerides.• Increases HDL cholesterol.Increases HDL cholesterol.• Can be used in renal insufficiency. Can be used in renal insufficiency.
Contra-indicationsContra-indications• Impaired renal and hepatic function. Impaired renal and hepatic function.
• Pregnancy Pregnancy
• Type 1 diabetesType 1 diabetes
• Thyroid and adrenal dysfunction.Thyroid and adrenal dysfunction.
DISADVANTAGESDISADVANTAGES• Hypoglycaemia – may be prolonged or Hypoglycaemia – may be prolonged or
severe.severe.• Weight gain.Weight gain.• Drug interactions, especially 1Drug interactions, especially 1stst generation. generation.• Hyponatraemia with Chlorpropamide.Hyponatraemia with Chlorpropamide.• Cannot use if allergic to SU compounds.Cannot use if allergic to SU compounds.• Direct Exocytosis of Beta cells: ? Beta cell Direct Exocytosis of Beta cells: ? Beta cell
secretion.secretion.• Physiologic route of insulin delivery.Physiologic route of insulin delivery.• Permits flexibility in lifestyle: Dose coupled to meals –Permits flexibility in lifestyle: Dose coupled to meals –
no need for snacking-promote weight loss.no need for snacking-promote weight loss.• High initial response rate.High initial response rate.• No lag period before response.No lag period before response.• Can be used in various degrees of renal impairment.Can be used in various degrees of renal impairment.• Low incidence of severe hypoglycaemic episodes.Low incidence of severe hypoglycaemic episodes.
Alpha-Glucosidase InhibitorsAlpha-Glucosidase InhibitorsMechanism of actionMechanism of action
• Acts by competitive inhibition of alpha-Acts by competitive inhibition of alpha-glucosidase enzymes.glucosidase enzymes.
• Reduces the rate of monosaccharide Reduces the rate of monosaccharide generation and absorption.generation and absorption.
• Delays glucose absorption in the intestine.Delays glucose absorption in the intestine.• Modulates peaks in post-prandial glucose.Modulates peaks in post-prandial glucose.• Taken with meals.Taken with meals.
ADVANTAGESADVANTAGES• Good safety profile.Good safety profile.• No weight gain.No weight gain.• Dose coupled to meals.Dose coupled to meals.• Unique mechanism.Unique mechanism.
Rationale for COMBINATION Rationale for COMBINATION THERAPYTHERAPY
• Improving Improving metabolic metabolic effect by combining effect by combining drugs with drugs with different different mechanisms of action.mechanisms of action.
• Reducing Reducing side effectsside effects by sub-maximal by sub-maximal dosage.dosage.
• Starting combination therapy according to Starting combination therapy according to metabolic guidelinesmetabolic guidelines..
• Prescribing drugs according to Prescribing drugs according to individual individual patient need.patient need.
Management of patients Management of patients prsenting with very high Blood prsenting with very high Blood Glucose levels.Glucose levels.
• Level higher than~Level higher than~20mmol/L20mmol/L-admission into -admission into hospital,hospital, depending on symptoms. depending on symptoms.
• If type of diabetes is uncertain - If type of diabetes is uncertain - C-peptideC-peptide test needed. Check for blood/urine test needed. Check for blood/urine ketones.ketones.
Initiation of insulin may be necessary: Initiation of insulin may be necessary: • Use Use supplementation/adjustment scalesupplementation/adjustment scale..• Work insulin dosage out according to Work insulin dosage out according to
Body weight.Body weight.• Adjust insulin dosage according to Adjust insulin dosage according to blood blood
glucose readings.glucose readings.
Insulin adjustment scale Insulin adjustment scale Eg. Of patients on basal-bolus regimenEg. Of patients on basal-bolus regimen
Pre-meal readingPre-meal reading
Change insulinChange insulin
Decrease 1-3 unitsDecrease 1-3 units
Decrease 0-1 unitsDecrease 0-1 units
Increase 0-1 unitsIncrease 0-1 units
Increase 1-2 unitsIncrease 1-2 units
Increase 2-3 unitsIncrease 2-3 units
Increase 3-4 unitsIncrease 3-4 units
Increase 4-6 unitsIncrease 4-6 units
When and how to start insulin When and how to start insulin treatment in type 2 diabetes.treatment in type 2 diabetes.
Insulin therapy in Type 2 patients on Insulin therapy in Type 2 patients on OAD’s can be started in two ways:OAD’s can be started in two ways:
• Continue OAA treatment.Continue OAA treatment.• Add 02iu/kg NPH at breakfast or at bedtime.Add 02iu/kg NPH at breakfast or at bedtime.• Dose increase by 2-4iu every 3-4 days, if Dose increase by 2-4iu every 3-4 days, if
necessary.necessary.• If more than 36iu insulin needed to obtain If more than 36iu insulin needed to obtain
control – stop OAA treatment and continue control – stop OAA treatment and continue insulin alone.insulin alone.
1.1. Treat the patient not the glucometer.Treat the patient not the glucometer.2.2. Control other risk factors:Control other risk factors:3.3. ObesityObesity – life style modification – life style modification
drug therapy drug therapy4.4. DislipidaemiaDislipidaemia5.5. Hypertension Hypertension – – drug side effects drug side effects
• Elevated Elevated postprandial blood glucosepostprandial blood glucose = risk = risk factor for Cardiovascular disease and factor for Cardiovascular disease and mortality, independent of Fasting blood mortality, independent of Fasting blood glucose levels and HbAglucose levels and HbA1C1C..
• Early and aggressiveEarly and aggressive treatment of Type 2 treatment of Type 2 diabetes, to improve glycaemic control, diabetes, to improve glycaemic control, decreases the risk of long term complications.decreases the risk of long term complications.
• Insulin treatment initiated when near Insulin treatment initiated when near normalizationnormalization of BG cannt be achieved with of BG cannt be achieved with OAA’s alone.OAA’s alone.
• Better BG control – reduces/avoids Better BG control – reduces/avoids atherosclerosis – atherosclerosis – BP managementBP management..
• Education on Education on dislipidemia.dislipidemia.• Quality of Quality of Life factorsLife factors affect control and affect control and