THERAPEUTICS I

Class 7
Alicia E. Frederick
Cert. Pharm.
Dip. Pharm. (Hons)
B. Pharm. (Hons)
Pharm. D. Candidate
DIABETES MELLITUS

• (Chapter 53)

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OVERVIEW
THE ENOCRINE SYSTEM – A REVIEW

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 Definition of Diabetes
• A group of metabolic disorders of fat, carbohydrate and protein
metabolism that results from defects in insulin secretion, insulin
action (sensitivity) or both.
• It is characterized by hyperglycaemia

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LOCATION OF THE PANCREAS

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 Classification of Diabetes
• Type 1 – absolute deficiency of insulin
• Autimmune
• Acute onset – usually months to 1 year
• Type 2 – insulin resistance with inadequate compensatory increase
in insulin secretion
• Chronic onset – usually 9-12 years
• Gestational diabetes – glucose intolerance first recognized during
pregnancy.

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 Classification of Diabetes cont’d
• Latent Autoimmune Diabetes in Adults (LADA)
• A.k.a. type 1.5
• Acute onset – usually 1-3 years
• Other – uncommon types of diabetes caused by:
• Infections,
• drugs
• endocrinopathies
• pancreatic destruction
• genetic defects.

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TYPE 1
 Pathophysiology of Type 1 DM
• Absolute insulin deficiency
• Autoimmune destruction of β cells of the pancreas
• Genetic predisposition
• Environmental factors
• Onset in early years but can occur at any age
• Typically associated with ketoacidosis

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 Pharmacotherapy for Type 1 Diabetes
Recommendations:
• use of multiple dose insulin injections (3–4 injections per day of
basal and prandial insulin) or CSII therapy
• matching of prandial insulin to carbohydrate intake, pre-meal
blood glucose, and anticipated activity
• use of insulin analogs for some patients (especially if hypoglycemia
is a problem)

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PHARMACOTHERAPY FOR TYPE 1 DIABETES
• Rapid Acting Insulin • Long Acting Insulin
• Insulin lispro • Insulin detemir
• Insulin aspart • Insulin glargine
• Insulin glulisine • Pramlintide
• Short Acting Insulin ( Symlin)
• Regular
• Intermediate Acting Insulin
• NPH
• Lente
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TYPE 2
 Pathophysiology of Type 2 DM
• Insulin resistance and relative lack of insulin secretion
• Progressively lower insulin secretion over time
• Impaired insulin secretion due to:
• Liver - ↑hepatic gluconeogenesis
• Muscle - ↓ glucose uptake
• Adipocyte – failure of insulin to suppress breakdown of
triglycerides
• Elevated postprandial glucagon
• Loss of incretin effect
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 Insulin Resistance Syndrome/ Metabolic Syndrome

• Cluster of abnormalities often present in Type 2 diabetes

individuals
• Abdominal obesity
• Hypertension
• Dyslipidemia (↑TG and ↓HDL-cholesterol levels)
• Elevated plasminogen activator inhibitor type I (PAI – I) levels

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 Risk Factors for Type 2 DM
• Family history (parents or siblings)
• Obesity (≥ 20% over ideal body weight or BMI ≥ 25 kg/m2)
• Physical inactivity
• Race or ethnicity
• Hypertension
• History of gestational diabetes
• History of vascular disease

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 Type 1 vs Type 2 DM
Which of the following features is more consistent in Type 2 DM?
A. Onset in childhood
B. Absolute deficiency of insulin
C. Obesity
D. Presence of ketoacidosis

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 Symptoms of Diabetes & Hyperglycemia
• Classic Symptoms (normally found in Type 1DM)
• Polyuria
• Polydipsia
• polyphagia
• Blurred vision
• Fatigue/weakness
• Ketoacidosis (Type 1DM)

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 Symptoms of Diabetes & Hyperglycemia cont’d
• Type 2 may be asymptomatic
• Elevated BG level
• In older obese patients:
• Glucosuria
• Proteinuria
• Microaneurysms
• Retinal exudates
• Hyperglycemia
• Blurred vision,tingling and numbness in feet, slow-healing skin
infections, itching, drowsiness, irritability 21
 Diagnosis of Diabetes
• Symptoms of diabetes plus casual plasma glucose concentrations ≥
200mg/dL (11.1 mmol/L)
• Fasting BG ≥ 126mg/dL (7.0 mmol/L)
• 2-hour postload glucose ≥ 200mg/dL (11.1 mmol/L) during OGTT
• Confirm with a repeat test
• HbA1c ≥ 6.5%

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 Haemoglobin A1c
• Increases with increasing blood sugar
• Correlates with average blood sugar
• Reflects control over last 3 months
• Normal value 4-6% traditionally
• Pre-diabetes = 5.7-6.4%

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 Haemoglobin A1c for Diagnosis
• Advantages
• Convenient – no need for fasting
• Less day to day variation
• Disadvantages
• More expensive
• Lack of correlation with BG in some patients

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 HbA1c and correlation with BG (old method)
• A1c of 6% = average plasma glucose of 135mg/dL
• Add 35 mg/dL for every 1% increase
• 7% = 170
• 8% = 205
• 9% = 240

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 A1c and estimated Average Glucose (eAG)
• Method of expressing A1c as average glucose
• A1C-Derived Average Glucose study (ADAG), affirmed the
existence of a linear relationship between A1C and average blood
glucose levels.
• ADA now recommends the use of estimated average glucose, eAG.
• HCPs can now report A1C results to patients using the same units
(mg/dl or mmol/l) that patients see routinely in blood glucose
measurements
• The relationship between A1C and eAG is described by the
formula 28.7 X A1C – 46.7 = eAG (mg/dl) 26
 A1c and Estimated Average Glucose (eAG)

A1c eAG

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 Recommendations for use of A1c
• Perform the A1C test at least two times a year in patients who are
meeting treatment goals (and who have stable glycemic control).
• Perform the A1C test quarterly in patients whose therapy has
changed or who are not meeting glycemic goals.
• Use of point-of-care testing for A1C allows for timely decisions on
therapy changes, when needed.

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Glycemic Goals of Therapy
Biochemical Index Normal

Haemoglobin A1c < 6%

Preprandial (2h) BG <100 mg/dL

Postprandial BG < 140 mg/dL

(1-2 hours after start
of meal)
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 Goals of Therapy
• Blood Pressure < 140/90
• Lipid Levels:
• LDL < 100mg/dL
• HDL > 40 mg/dL
• TG < 150 mg/dL
• More aggressive LDL goals in some patients

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 Treatment Objectives for DM
• Normalize glucose metabolism
– maintain recommended treatment goals
• Avoid symptoms of DM
• Avoid frequent hypoglycaemia
• Normalize nutrition and achieve ideal body weight
• Achieve normal growth and development
• Minimize or prevent complications
• Maintain normal and flexible lifestyle
• Promote emotional wellbeing: teach patient to take charge of the condition
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 Management of DM
• Successful management of DM combines a program of:
• Weight maintenance or reduction
• Diet
• Individualized exercise programme
• Medications
• Diabetes education

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 Management Plan
 Involves individualized therapeutic alliance between patient,
family, and members of the health care team.
 Strategies and techniques should provide adequate education
and development of problem-solving skills in all aspects of
diabetes management.
 Implementation of the plan requires understanding and
agreement among the parties and the goals and treatment plan
should be reasonable.

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PHARMACOTHERAPY FOR TYPE 2 DIABETES
• Sulphonylureas (e.g., glimepiride) • Glucagon-like peptide-1
• Biguanides (e.g., metformin) receptor agonist (GLP-1 RA)
• Glinides (e.g., repaglinide) e.g. exenatide
• Thiazolidinediones (e.g., pioglitazone) • Pramlintide
• Dipeptidyl peptidase IV inhibitors
(e.g., sitagliptin)
• Insulin
• α-glucosidase inhibitors (e.g.,
acarbose)
• Sodium glucose co-transporter 2
(SGLT2) inhibitors e.g. empagliflozin

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MEDICAL NUTRITION THERAPY (MNT)
• Type 1 Diet
• Type 2 Diet
• Daily calories count :
• carbohydrates - 50% to 60%
• protein - 12% to 20%
• fat - not more than 30% (with
no more than 10 percent
from saturated fats)
• Nutritionist

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 Exercise
• At least 150 min/week of moderate-intensity aerobic physical activity
• In the absence of contraindications, people with type 2 diabetes should be
encouraged to perform resistance training at least twice per week
• Regular exercise has been shown to improve blood glucose control, reduce
cardiovascular risk factors, contribute to weight loss, and improve well-
being.
• Structured exercise interventions of at least 8-week duration have been
shown to lower A1C by an average of 0.66% in people with type 2 diabetes,
even with no significant change in BMI
• Higher levels of exercise intensity are associated with greater improvements
in A1C and in fitness.
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 Exercise cont’d
• Improves glycemic control
• Regular exercise may prevent type 2 diabetes in high-risk
individuals
• Creates risk of hypoglycemia
• Increase as tolerated

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 Diabetes Education
• Self Monitoring of Blood Glucose (SMBG)
• Complications of Diabetes
• Foot Care
• Eye Care
• Dental Care

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 Education - Insulin Use
• Injection Technique
• Mixing Insulin
• Storage of Insulin
• Refrigerate if not in use
• Stable at room temperature for 1 month
• Prefilled syringes

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COMPLICATIONS OF DM
 Diabetic Complications
Acute Complications
• Diabetic Ketoacidosis
• Hyperglycemic Hyperosmolar nonketotic syndrome (HHNS)
• Hypoglycemia
• Hyperglycemia

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 Diabetic Complications

• Chronic Complications
• Microvascular
• Peripheral neuropathy
• Autonomic neuropathy
• Retinopathy
• Nephropathy
• Macrovascular
• Myocardial infarction
• Stroke 42
Foot Care
• Inspect feet daily – link foot checks with daily routine habit such
as bathing.
• Look for redness, swelling, cuts, blisters, calluses, dryness,
cracks, corns and any changes in appearance.
• Check for changes in temperature. Unusual coldness may
indicate a problem.
• Seek medical attention if any lesion does not improve within 48
hours

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 Foot Care cont’d
• Refer patients to podiatrist for regular toenail care.
• Apply alcohol-free moisturizers to feet, not between toes, to
prevent drying and cracking.
• Wear properly fitted footwear – socks and shoes
• Avoid walking barefooted
• Cut toenails straight across

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Benefits of Strict Glycemic Control
• 39% reduction in development of microalbuminemia.
• 54% reduction in development of macroalbuminemia
• 60% reduction in development of clinical neuropathy
• 34-76% reduction in development of clinically significant
retinopathy
• 47% reduction in progression to severe retinopathy.

DCCT Study. NEJM. 1993; 329: 977-86

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 Importance of Adequate Control
• Glycemic Control
• 1% decrease in HBA1c = 40% decrease in microvascular
complications
• Blood Pressure Control
• Reduces risk of heart disease and stroke by 33-50%
• Reduces risk of microvascular complications by 33%
• Lipid Control
• Reduces cardiovascular complications by 20-50%

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Glucose Monitoring - Recommendations

• SMBG should be carried out 3 or more times daily for patients

using multiple insulin injections or insulin pump therapy.
• For patients using less-frequent insulin injections, noninsulin
therapies, or medical nutrition therapy (MNT) alone, SMBG may be
useful as a guide to management.
• To achieve postprandial glucose targets, postprandial SMBG may
be appropriate.

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 Glucose Monitoring - Recommendations
 When prescribing SMBG, ensure that patients receive initial
instruction in, and routine follow-up evaluation of, SMBG technique
and their ability to use data to adjust therapy.
 Continuous glucose monitoring (CGM) in conjunction with intensive
insulin regimens can be a useful tool to lower A1C in selected adults
(age ≥25 years) with type 1 diabetes.

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 Role of the Pharmacist in Diabetes Management

• Screening for Diabetes

• Patient Education
• Monitoring of diabetes
• Referral to other members of the diabetes care team
• Certification - CDE

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PHARMACOTHERAPY
OF TYPE 2 DM
SEE Guidelines (Moodle)

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REFERENCES

• Applied Therapeutics: The Clinical Use of Drugs, Caroline S. Zeind &

Michael G. Carvalho, 11th Edition. LWW (December 27, 2017)
• Pharmacotherapy: A Pathophysiologic Approach, Joseph DiPiro et
al, 10th Edition. McGraw Hill / Medical (December 13, 2016)
• AK. Soyibo, Caribbean Institute of Nephrology Department of
Medicine

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