Drug therapy in Diabetes

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Drug therapy in Diabetes

• Dr K S Myint
• Specialist Registrar

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Diagnosis of Diabetes
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Aims of management

• To achieve near normal glycaemia
• Short term- to prevent symptoms of hyper hypo
• Long term- to prevent complications
• Good quality of life, near normal life expectancy

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Targets for non-pregnant patients

• HbA1c - NICE 6.5-7.5
• - ADA lt7
• - IDF lt6.5
• BP - lt130/80
• Cholesterol- LDL lt2.6 (mM)
• HDL gt1.1
• TG lt1.7

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Types of Insulin

• Short acting - Soluble / Neutral insulin
• Insulin aspart
• Insulin lispro
• Intermediate acting - Isophane
• Long acting - Insulin Zinc suspension
• new insulin analogue - Glargine
• Detemir
• Biphasic- mixture of short and intermediate
• Biphasic lispro
• Biphasic Isophane

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Types of Insulin
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Soluble insulin / neutral /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 lt 5 min, required continuous
  infusion
• Used in diabetes Ketoacidosis

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Sites of injections - Subcutaneous

• Thighs
• Upper buttocks
• Abdomen
• Arms
• Important to rotate the site
• Rate of absorption may be significantly different
  faster from arm and abdomen than from thigh and
  buttock

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Routes of Administration

• Subcutaneous for long term regular use
• Intravenous infusion in acute conditions-
  diabetes Ketoacidosis, Perioperative period,
  Hyperosmolar Nonketotic state ONLY NEUTRAL/
  CLEAR INSULIN CAN BE USED
• Continuous subcutaneous insulin infusion via pump
  neutral
• Intraperitoneal Peritoneal dialysis patients
• Inhaled insulin- experimental

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Untoward effect of insulin

• Hypoglycaemia
• Weight gain- anabolic hormone
• Lipohypertrophy- injection to same site
• Insulin oedema
• Transient deterioration in retinopathy
• Insulin neuritis actively regenerating neurone,
  uncommon
• Postural hypotension

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Example
bedtime
injections
Intermediate/long acting
bedtime
injections
Biphasic insulin
Biphasic insulin
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Recurrent Hypo

• ? Required dose adjustment
• ? Right insulin/ injection technique
• ? Meal/ fasting related
• ? Injections sites
• ? Exercise
• Unexplained - ?autonomic neuropathy

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Sick day rules

• never stop insulin
• monitor more frequently
• maintain your hydration
• Check for ketones
• Know when how to call for help

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Oral Medications to Treat Type 2 Diabetes
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Major Classes of Medications

• Thiazolidinediones
• Biguanides
• Sulfonylureas
• Meglitinides
• Alpha-glucosidase
• inhibitors

• sensitize the body to insulin /- control
  hepatic glucose production
• stimulate the pancreas to make more insulin
• slow the absorption of starches

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Thiazolidinediones

• ? insulin resistance by making muscle and adipose
  cells more sensitive to insulin. They also
  suppress hepatic glucose production.
• Efficacy
• ? fasting plasma glucose 1.9-2.2 mmol/L
• Reduce A1C 0.5-1.0
• 6 weeks for maximum effect
• Other Effects
• Weight gain, oedema
• Hypoglycemia (if taken with insulin or agents
  that stimulate insulin release)
• Contraindicated in patients with abnormal LFT or
  CHF
• Improves HDL cholesterol and plasma
  triglycerides usually LDL neutral
• Medications in this Class pioglitazone (Actos),
  rosiglitazone (Avandia), troglitazone (Rezulin)
  - taken off market due to liver toxicity

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Biguanides

• Biguanides ? hepatic glucose production and
  increase insulin-mediated peripheral glucose
  uptake.
• Efficacy
• Decrease fasting plasma glucose 60-70 mg/dl
  (3.3-3.9 mmol/L)
• Reduce A1C 1.0-2.0
• Other Effects
• Diarrhea and abdominal discomfort
• Lactic acidosis if improperly prescribed
• Cause small decrease in LDL cholesterol level and
  triglycerides
• No specific effect on blood pressure
• No weight gain, with possible modest weight loss
• Contraindicated in patients with impaired renal
  function
• Medications in this Class metformin
  (Glucophage), metformin hydrochloride extended
  release (Glucophage XR)

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Sulfonylureas

• Sulfonylureas increase endogenous insulin
  secretion
• Efficacy
• Decrease fasting plasma glucose 3.3-3.9 mmol/L
• Reduce A1C by 1.0-2.0
• Other Effects
• Hypoglycemia
• Weight gain
• No specific effect on plasma lipids or blood
  pressure
• Generally the least expensive class of medication
• Medications in this Class
• First generation chlorpropamide , tolazamide,
  acetohexamide , tolbutamide
• Second generation glyburide , glimepiride ,
  glipizide

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Meglitinides

• stimulate insulin secretion (rapidly and for a
  short duration) in the presence of glucose.
• Efficacy
• ? peak postprandial glucose
• ? plasma glucose 3.3-3.9 mmol/L
• ? HbA1C 1.0-2.0
• Other Effects
• Hypoglycemia (may be less than with sulfonylureas
  if patient has a variable eating schedule)
• Weight gain
• No significant effect on plasma lipid levels
• Safe at higher levels of serum Cr than
  sulfonylureas
• Medications in this Class repaglinide ,
  nateglinide

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Alpha-glucosidase Inhibitors

• Alpha-glucosidase inhibitors block the enzymes
  that digest starches in the small intestine
• Efficacy
• ? peak postprandial glucose 2.2-2.8 mmol/L
• ? fasting plasma glucose 1.4-1.7 mmol/L
• Decrease A1C 0.5-1.0
• Other Effects
• Flatulence or abdominal discomfort
• No specific effect on lipids or blood pressure
• No weight gain
• Contraindicated in patients with inflammatory
  bowel disease or cirrhosis
• Medications in this Class acarbose , miglitol

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Efficacy of Monotherapy with Oral Diabetes Agents
DeFronzo Annals of Internal Medicine
1999131281-303 Nathan N Engl J Med 2002
3471342-1349
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Treatment of Type 2 Diabetes
Diagnosis
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Combination Therapy for Type 2 Diabetes
Fixed Combination Pills

• Sulfonylurea Biguanide
• Glyburide Metformin - Glucovance
• Glipizide Metformin - Metaglip
• Thiazolidinedione Biguanide
• Rosiglitazone Metformin - Avandamet

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Combination Therapy for Type 2 Diabetes
Sulfonylureas
Biguanides
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Clinic Checklists

• Glycaemic control- home monitoring, HbA1c, inj
  site, hypo
• Diet, exercise, Smoking, alcohol
• BP
• Weight
• Macrovascular- CVA, IHD
• Microvascular- Retinopathy, microalbuminuria,
  neuropathy
• Foot
• Lipid profile, renal function, TSH

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Special circumstances

• Intercurrent illness
• Peri-operative period
• Pregnancy
• Childhood and adolescents
• Others- travelling across time zones
• Exercise
• Alcohol
• Driving

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New developments
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