Drug therapy in Drug therapy in DiabetesDiabetes
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Diagnosis of DiabetesDiagnosis of Diabetes
Fasting Random OGTT(2h)
Normal <6 <7.8Impair 6.1 – 7 7.8- 11.1Diabetes >7 >11.1 +
symptoms
>11.1
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Aims of managementAims of management
To achieve near normal glycaemiaTo achieve near normal glycaemia- Short term- to prevent symptoms of Short term- to prevent symptoms of
hyper & hypohyper & hypo- Long term- to prevent complicationsLong term- to prevent complications Good quality of life, near normal life Good quality of life, near normal life
expectancyexpectancy
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Targets for non-pregnant Targets for non-pregnant patientspatients
HbA1c - NICE HbA1c - NICE 6.5-7.5% 6.5-7.5%
- ADA- ADA <7%<7%
- IDF- IDF <6.5%<6.5% BPBP - <130/80- <130/80 Cholesterol- LDL <2.6 (mM)Cholesterol- LDL <2.6 (mM)
HDL >1.1 HDL >1.1
TG <1.7 TG <1.7
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Types of InsulinTypes of Insulin Short acting - Short acting - Soluble / Neutral insulinSoluble / Neutral insulin Insulin aspartInsulin aspart Insulin lisproInsulin lispro Intermediate acting - IsophaneIntermediate acting - Isophane Long acting - Insulin Zinc suspensionLong acting - Insulin Zinc suspension
new insulin analogue - Glargine new insulin analogue - Glargine Detemir Detemir
Biphasic- mixture of short and intermediateBiphasic- mixture of short and intermediate Biphasic lisproBiphasic lispro Biphasic IsophaneBiphasic Isophane
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Types of InsulinTypes of InsulinInsulin Lispro
AspartNeutral/regular
Isophane ultratard Glargine
Onset 10-20′ 30′ 1h 4h 2-4h
Peak 1h 1-3h 4-6h 6-18h peak less
Duration 3-5h 4-8h 8-14h 24h 20-24h
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Soluble insulin / Soluble insulin / neutral /clearneutral /clear
Names - Human actrapid/ Humulin S Species- Bovine, porcine, human Following s/c injection
Onset of action – 30 min Peak- 1-3 hours Duration- 4-8 hours
Only insulin suitable for intravenous route –plasma half life < 5 min, required continuous infusion
Used in diabetes Ketoacidosis
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Sites of injections - Sites of injections - SubcutaneousSubcutaneous
ThighsThighs Upper buttocksUpper buttocks AbdomenAbdomen ArmsArms
Important to rotate the siteImportant to rotate the site
Rate of absorption may be significantly Rate of absorption may be significantly different – faster from arm and different – faster from arm and abdomen than from thigh and buttockabdomen than from thigh and buttock
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Routes of AdministrationRoutes of Administration
Subcutaneous for long term regular useSubcutaneous for long term regular use Intravenous infusion in acute conditions- Intravenous infusion in acute conditions-
diabetes Ketoacidosis, Perioperative diabetes Ketoacidosis, Perioperative period, Hyperosmolar Nonketotic state period, Hyperosmolar Nonketotic state ONLY NEUTRAL/ CLEAR INSULIN CAN BE ONLY NEUTRAL/ CLEAR INSULIN CAN BE USEDUSED
Continuous subcutaneous insulin infusion Continuous subcutaneous insulin infusion via pump – neutralvia pump – neutral
Intraperitoneal – Peritoneal dialysis Intraperitoneal – Peritoneal dialysis patientspatients
Inhaled insulin- experimentalInhaled insulin- experimental
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Untoward effect of Untoward effect of insulininsulin
HypoglycaemiaHypoglycaemia Weight gain- anabolic hormoneWeight gain- anabolic hormone Lipohypertrophy- injection to same siteLipohypertrophy- injection to same site Insulin oedemaInsulin oedema Transient deterioration in retinopathyTransient deterioration in retinopathy Insulin neuritis – actively regenerating Insulin neuritis – actively regenerating
neurone, uncommonneurone, uncommon Postural hypotensionPostural hypotension
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ExampleExample
injections
Short actingShort acting Short actingIntermediate/long acting
breakfast lunch dinner
breakfast lunch dinner bedtime
bedtimeinjections
Biphasic insulin Biphasic insulinwww.freelivedoctor.com
Recurrent HypoRecurrent Hypo ? Required dose adjustment? Required dose adjustment ? Right insulin/ injection technique? Right insulin/ injection technique ? Meal/ fasting related? Meal/ fasting related ? Injections sites? Injections sites ? Exercise? Exercise Unexplained - ?autonomic Unexplained - ?autonomic
neuropathyneuropathy
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Sick day rulesSick day rules
never stop insulinnever stop insulin monitor more frequentlymonitor more frequently maintain your hydrationmaintain your hydration Check for ketonesCheck for ketones Know when & how to call for helpKnow when & how to call for help
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Oral Medications Oral Medications to Treat Type 2 to Treat Type 2
DiabetesDiabetes
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Major Classes of Major Classes of MedicationsMedications
sensitize the sensitize the body to insulin body to insulin +/- control +/- control hepatic glucose hepatic glucose productionproduction
stimulate the stimulate the pancreas to pancreas to make more make more insulininsulin
slow the slow the absorption of absorption of starches starches
ThiazolidinedionesThiazolidinediones
BiguanidesBiguanides
SulfonylureasSulfonylureas
MeglitinidesMeglitinides
Alpha-glucosidaseAlpha-glucosidase
inhibitorsinhibitors
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ThiazolidinedionesThiazolidinediones ↓↓ insulin resistance by making muscle and adipose cells insulin resistance by making muscle and adipose cells
more sensitive to insulin. They also suppress hepatic more sensitive to insulin. They also suppress hepatic glucose production.glucose production.
EfficacyEfficacy ↓↓ fasting plasma glucose ~1.9-2.2 mmol/Lfasting plasma glucose ~1.9-2.2 mmol/L Reduce A1C ~0.5-1.0%Reduce A1C ~0.5-1.0% 6 weeks for maximum effect6 weeks for maximum effect
Other EffectsOther Effects Weight gain, oedema Weight gain, oedema Hypoglycemia (if taken with insulin or agents that Hypoglycemia (if taken with insulin or agents that
stimulate insulin release)stimulate insulin release) Contraindicated in patients with abnormal LFT or CHFContraindicated in patients with abnormal LFT or CHF Improves HDL cholesterol and plasma triglycerides; Improves HDL cholesterol and plasma triglycerides;
usually LDL neutralusually LDL neutral Medications in this Class: pioglitazone (Actos), Medications in this Class: pioglitazone (Actos),
rosiglitazone (Avandia), [troglitazone (Rezulin) - taken off rosiglitazone (Avandia), [troglitazone (Rezulin) - taken off market due to liver toxicity]market due to liver toxicity]www.freelivedoctor.com
BiguanidesBiguanides Biguanides Biguanides ↓↓ hepatic glucose production and hepatic glucose production and
increase insulin-mediated peripheral glucose increase insulin-mediated peripheral glucose uptake.uptake.
EfficacyEfficacy Decrease fasting plasma glucose 60-70 mg/dl (3.3-3.9 Decrease fasting plasma glucose 60-70 mg/dl (3.3-3.9
mmol/L)mmol/L) Reduce A1C 1.0-2.0%Reduce A1C 1.0-2.0%
Other EffectsOther Effects Diarrhea and abdominal discomfortDiarrhea and abdominal discomfort Lactic acidosis if improperly prescribedLactic acidosis if improperly prescribed Cause small decrease in LDL cholesterol level and Cause small decrease in LDL cholesterol level and
triglyceridestriglycerides No specific effect on blood pressureNo specific effect on blood pressure No weight gain, with possible modest weight lossNo weight gain, with possible modest weight loss Contraindicated in patients with impaired renal function Contraindicated in patients with impaired renal function Medications in this Class: metformin (Glucophage), Medications in this Class: metformin (Glucophage),
metformin hydrochloride extended release (Glucophage XR)metformin hydrochloride extended release (Glucophage XR)www.freelivedoctor.com
SulfonylureasSulfonylureas Sulfonylureas increase endogenous insulin Sulfonylureas increase endogenous insulin
secretionsecretion EfficacyEfficacy
Decrease fasting plasma glucose 3.3-3.9 mmol/LDecrease fasting plasma glucose 3.3-3.9 mmol/L Reduce A1C by 1.0-2.0%Reduce A1C by 1.0-2.0%
Other EffectsOther Effects HypoglycemiaHypoglycemia Weight gain Weight gain No specific effect on plasma lipids or blood pressureNo specific effect on plasma lipids or blood pressure Generally the least expensive class of medicationGenerally the least expensive class of medication
Medications in this Class:Medications in this Class: First generation : chlorpropamide , tolazamide, First generation : chlorpropamide , tolazamide,
acetohexamide , tolbutamideacetohexamide , tolbutamide Second generation : glyburide , glimepiride , glipizide Second generation : glyburide , glimepiride , glipizide www.freelivedoctor.com
MeglitinidesMeglitinides stimulate insulin secretion (rapidly and for a stimulate insulin secretion (rapidly and for a
short duration) in the presence of glucose.short duration) in the presence of glucose. EfficacyEfficacy
↓↓ peak postprandial glucosepeak postprandial glucose ↓↓ plasma glucose 3.3-3.9 mmol/Lplasma glucose 3.3-3.9 mmol/L ↓↓ HbA1C 1.0-2.0%HbA1C 1.0-2.0%
Other EffectsOther Effects Hypoglycemia (may be less than with sulfonylureas if Hypoglycemia (may be less than with sulfonylureas if
patient has a variable eating schedule)patient has a variable eating schedule) Weight gain Weight gain No significant effect on plasma lipid levelsNo significant effect on plasma lipid levels Safe at higher levels of serum Cr than sulfonylureasSafe at higher levels of serum Cr than sulfonylureas
Medications in this Class: repaglinide , nateglinideMedications in this Class: repaglinide , nateglinide
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Alpha-glucosidase Alpha-glucosidase InhibitorsInhibitors Alpha-glucosidase inhibitors block the enzymes Alpha-glucosidase inhibitors block the enzymes
that digest starches in the small intestinethat digest starches in the small intestine EfficacyEfficacy
↓↓ peak postprandial glucose 2.2-2.8 mmol/Lpeak postprandial glucose 2.2-2.8 mmol/L ↓↓ fasting plasma glucose 1.4-1.7 mmol/Lfasting plasma glucose 1.4-1.7 mmol/L Decrease A1C 0.5-1.0%Decrease A1C 0.5-1.0%
Other EffectsOther Effects Flatulence or abdominal discomfort Flatulence or abdominal discomfort No specific effect on lipids or blood pressureNo specific effect on lipids or blood pressure No weight gainNo weight gain Contraindicated in patients with inflammatory Contraindicated in patients with inflammatory
bowel disease or cirrhosisbowel disease or cirrhosis Medications in this Class: acarbose , miglitol Medications in this Class: acarbose , miglitol
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Efficacy of Efficacy of Monotherapy with Oral Monotherapy with Oral
Diabetes AgentsDiabetes AgentsDrug Fasting Plasma
Glucose Reduction (mmol/l)
A1C Reduction
(%) Thiazolidinedione 1.9-2.2 0.5-1.0
Sulfonylurea 3.3-3.9 1.0-2.0
Biguanide 3.3-3.9 1.0-2.0
Meglitinide 3.3-3.9 1.0-2.0
Alpha-glucosidase inhibitor
1.4-1.7 0.5-1.0
DeFronzo Annals of Internal Medicine 1999;131:281-303
Nathan N Engl J Med 2002; 347:1342-1349 www.freelivedoctor.com
Treatment of Type 2 Treatment of Type 2 DiabetesDiabetes
DiagnosisDiagnosis
Therapeutic Lifestyle ChangeTherapeutic Lifestyle Change
Combination Therapy - Oral Drug with InsulinCombination Therapy - Oral Drug with Insulin
Combination Therapy - Oral Drugs OnlyCombination Therapy - Oral Drugs Only
MonotherapyMonotherapy
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Sulfonylurea + Biguanide Sulfonylurea + Biguanide Glyburide + Metformin - Glyburide + Metformin -
GlucovanceGlucovance Glipizide + Metformin - Glipizide + Metformin - MetaglipMetaglip
Thiazolidinedione + BiguanideThiazolidinedione + Biguanide Rosiglitazone + Metformin - Rosiglitazone + Metformin - Avandamet Avandamet
Fixed Combination Pills
Combination Therapy for Type 2 Combination Therapy for Type 2 DiabetesDiabetes
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Combination Therapy for Type 2 Diabetes
Combination Therapy for Type 2 Diabetes
BiguanidesBiguanides
InsulinInsulin
SulfonylureasSulfonylureas
Alpha-glucosidase Inhibitors
Alpha-glucosidase Inhibitors
MeglitinideMeglitinide
ThiazolidinedionesThiazolidinediones
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Clinic ChecklistsClinic Checklists Glycaemic control- home monitoring, Glycaemic control- home monitoring,
HbA1c, inj site, hypoHbA1c, inj site, hypo Diet, exercise, Smoking, alcohol Diet, exercise, Smoking, alcohol BPBP WeightWeight Macrovascular- CVA, IHDMacrovascular- CVA, IHD Microvascular- Retinopathy, Microvascular- Retinopathy,
microalbuminuria, neuropathymicroalbuminuria, neuropathy Foot Foot Lipid profile, renal function, TSHLipid profile, renal function, TSH
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Special circumstancesSpecial circumstances Intercurrent illnessIntercurrent illness Peri-operative periodPeri-operative period PregnancyPregnancy Childhood and adolescentsChildhood and adolescents Others- travelling across time zonesOthers- travelling across time zones
ExerciseExercise
AlcoholAlcohol
DrivingDriving
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New developmentsNew developments
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