PHC576:

INTRODUCTION TO
DIABETES MELLITUS

Ms. Zakiah Mohd Noordin (RPh.)

Lecturer, Faculty of Pharmacy UiTM
 Learning Outcomes
By the end of the lecture, student should be able to:

• Describe the pathophysiology of diabetes mellitus

• Describe the common clinical presentations and etiologies of
diabetes mellitus
• Outline the evaluation in patients with diabetes mellitus
• Explain the treatment options available for patients with
diabetes mellitus
• Design plan for safety and efficacy monitoring of the
recommended pharmaceutical intervention
 What is Diabetes?
There are two main types of diabetes
• Type 1 - where the pancreas does not produce any insulin
• Type 2 - where the pancreas does not produce enough insulin -
or the body's cells do not react to insulin
 Scale of the Global Diabetes Crisis
Number of people with
diabetes worldwide and
per region in 2017 and
2045 (20-79 yrs)
 Prevalence of Type 2 DM in Malaysia
 T2DM: > 90% of all cases of adult-onset diabetes mellitus in
Malaysia.
 Overall diabetes prevalence in adults ≥ 18 years was 18.3% and
24.1% for adults ≥ 30 years
 TYPE 1
DIABETES MELLITUS
 Type 1 DM: Pathophysiology
“What once seemed like a single
autoimmune disorder, with roots
in T-cell mediated attack of
insulin-producing β cells, is now
recognised to result from a
complex interplay between
environmental factors and
microbiome, genome,
metabolism, and immune systems
that vary between individual
cases.”

DeMeglio et al Lancet 2018

 Type 1 DM: Stages

Greenbaum et al Diabetes 2018

Common symptoms: Risk factors:
• Thirst • Genetics
• Polyuria • Presence of GAD antibody and/or IA-2A
• Polydipsia • High birth weight (>4 kg)
• Early introduction of cow’s milk
• Recurrent
infection
• Weight loss
 TYPE 2
DIABETES MELLITUS
 Type 2 DM: Pathophysiology
• Progressive decline in beta-cell function associated with
insulin resistance in muscle and adipose tissue.
• Increased hepatic glucose output and reduced
utilisation of glucose  Fasting hyperglycaemia and
between meal hyperglycaemia.
• Impaired intestinal incretin secretion causes
compromised meal-related insulin secretion and
glucagon suppression contributing to postprandial
hyperglycaemia.
• Excessive renal tubular reabsorption of glucose further
contributes to hyperglycaemia.
Incretins and Glucose Homeostasis
Type 2 DM: Risk Factors
 Type 2 DM: Symptoms
 Fatigue
 Lethargy
 Polyuria
 Nocturia
 Polydipsia
 Type 2 DM: Diagnostic Tests
Fasting Plasma Glucose ≥ 7.0 mmol/L
Random Plasma Glucose ≥ 11 mmol/L
Oral Glucose Tolerence Test (2-hour) ≥ 11.1 mmol/L
HbAIC ≥ 6.3 %
(≥ 45 mmol/mol)
 Type 2 DM: Management
• Lifestyle modification, medications and patient education to encourage
self-care and empowerment
• The overall aims of management are to:
• improve quality of life
• reduce complications; and
• prevent premature death.
• Initial assessment in newly diagnosed T2DM:
• T2DM history
• Predisposition to T2DM
• Co-morbidities
• Medications and vaccinations
• Referrals
• Physical examination
• Baseline investigations (FPG, HbA1C, RP, LP, LFT, Urinalysis, ECG)
Type 2 DM Management: Targets for
Control
Type 2 DM Management: Diabetes
Education
Type 2 DM Management: Lifestyle
Modification
• Medical Nutrition Therapy
• Weight management
• For obese and overweight patients, weight loss of up to 10% of
initial body weight over a 6-month period
• Diet

• Physical activity
• At least 150 minutes/week of moderate-intensity and/or at least 75
minutes/week of vigorous aerobic and at least two sessions per
week of resistance exercise.
• Tobacco cessation
 Type 2 DM Management: Medications
• Oral Glucose Lowering Drugs
• Biguanides
• Sulphonylureas
• Meglitinides
• Alpha-glucose Inhibitors (AGIs)
• Thiazolidiones (TZD)
• Incretins – Dipeptidyl peptidase 4 inhibitor (DPP4-i)
• Sodium-glucose Cotransporter 2 inhibitors (SGLT2-i)

• Injectable Agents
• Glucagon-like peptide-1 receptor agonist (GLP1-RA)
• Insulin
• If targets are not met after optimal combined OGLDs therapy, consider adding
GLP-1RA or insulin.
 Type 2 DM Medications: Biguanides
• Lowers blood glucose especially fasting plasma glucose by decreasing
hepatic glucose production.
• AEs: nausea, anorexia and diarrhoea.
• These are minimised if metformin is taken together with/or after
meals.
• To reduce GI side effects, it is best to start with a single daily dose,
followed by weekly titration.
• Extended-release formulation also reduces these side effects.
• Low dose metformin can be safely prescribed to lactating mothers.
 Type 2 DM Medications: SU
• Reduce plasma glucose by increasing insulin secretion
• Hypoglycemia and weight gain are common
• More preferred: gliclazide, glipizide and glimepiride
• Glibenclamide not recommended for use in those above 60 years of
age.
• Highly protein bound
• Should be taken 10-30 minutes before meals
 Type 2 DM Medications: DPP4-i
• Prolong the half-life of endogenously produced GLP-1
• Stimulate glucose-dependent insulin secretion
• Partially reduce the elevated glucagon postprandially
• Weight neutral and have a minimal risk of hypoglycaemia
• Efficacious and safe in the elderly and all stages of DKD
 Type 2 DM Medications: SGLT2-i
• Selectively inhibits SGLT2, a transporter in the proximal tubule, thus
reducing glucose reabsorption leading to an increase in urinary glucose
excretion
• Weight loss and reduction in SBP and DBP
 Type 2 DM Medications: Meglitinides
• Short acting insulin secretagogues that bind to different sites within the SU
receptor.
• Should be taken within 10 minutes before main meals.
• Primarily used to control PPG and reduces HbA1c by 1.0%-1.2%.
• Associated with less risk of weight gain compared to SUs and hypoglycaemia
may be less frequent.

Type 2 DM Medications: AGIs

• Reduces the rate of absorption of polysaccharides in the proximal small intestine
by inhibiting α-glucosidase enzymes.
• Should be taken within meals.
• SEs: Bloating, abdominal discomfort, diarrhoea and flatulence
 Type 2 DM Medications: GLP1-RA
• Incretin mimetics: increases the secretion of insulin from the pancreas,
slows absorption of glucose from the gut, and reduces the action of
glucagon.
• SEs: nausea, vomiting and diarrhoea

• Should not be used in patients with a history of pancreatitis, patients with a

history of or a family history of MEN 2A or 2B or medullary thyroid cancer.
• Exenatide and Lixisenatide should not be used in patients with
gastroparesis.
 Type 2 DM Medications: Insulin
Consider insulin therapy in the following:
• Inadequate glycaemic control on optimal dose and number of OGLDs
• As short-term use
• acute illness or surgery
• pregnancy
• breast-feeding
• severe metabolic decompensation (DKA, HHS)
• As initial therapy in newly diagnosed T2DM;
• in presence of symptomatic hyperglycaemia and evidence of ongoing
catabolism
• when HbA1c >10% or FPG >13.0 mmol/L

• Types of insulin
• Prandial
• Basal
Basal insulin
• can be initiated at 10U a day or 0.1-0.2
U/kg/day,
• set FPG target and choose evidence-
based titration algorithm

Premixed insulin once or twice daily.

SU may need to be reduced/stopped

when intensifying insulin.
Type 2 DM: Treatment Algorithms
 Type 2 DM: Monitoring
• SMBG
• HbA1C
 7 Key points in the management of
Diabetes Mellitus
• Individualized glycaemic targets and glucose-lowering therapies.
• Diet, exercise, and education as the foundation of the treatment
program.
• Use of metformin as the optimal first-line drug unless
contraindicated.
• After metformin, the use of 1 or 2 additional oral or injectable
agents, with a goal of minimizing adverse effects if possible.
• Ultimately, insulin therapy alone or with other agents if needed to
maintain blood glucose control.
• Where possible, all treatment decisions should involve the patient,
with a focus on patient preferences, needs, and values.
• A major focus on comprehensive cardiovascular risk reduction.
 References
• Clinical Practice Guidelines (CPG) for the Management of
T2DM (6th Edition)
• Joseph T. DiPiro, Gary C. Yee, L. Michael Posey, Stuart T.
Haines, Thomas D. Nolin, Vicki Ellingrod, Pharmacotherapy: A
Pathophysiologic Approach, 11th, Mc-Graw Hill Education,
2020, ISBN: 9781260116816