Oral hypoglycaemic
agents
Diabetes Outreach
March 2011
Oral hypoglycaemic agents
Learning objectives
> Understand the progressive nature of type 2
diabetes and its impact on management.
> State the different types of oral
hypoglycaemic agents and how they are
used.
> Describe the main side effects of the
medications and implications for practice.
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Type 2 diabetes
> Pathophysiology involves both
– insulin resistance
– progressive failure of beta-cells to secrete insulin.
> Most people with type 2 diabetes ultimately
require insulin therapy to achieve glycaemic
goals.
> Combination therapy often necessary to
achieve optimal results (tablets and insulin).
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Meet Sue……..
> 47 year old current smoker.
> Presents to the GP complaining of recurrent
vaginal thrush, fatigue and frequent
urination.
> Previous medical history:
– gestational diabetes
Sue is newly diagnosed with type 2
diabetes
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Meet Sue.…….
Observations on examination
> 74kg and 165cm, BMI 27kg/m2.
> Random blood glucose level is 9.2mmol/L.
> Blood pressure 148/96mmHg.
> Total Cholesterol 6.2mmol/L.
– LDL-cholesterol 3.5mmol/L
– Triglycerides 1.2mmol/L
> Urinalysis is unremarkable.
> Results of glucose tolerance test confirm type 2
diabetes and HbA1c is 8.0%.
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What would you suggest for Sue?
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Algorithm for type 2 diabetes
Lifestyle modification
diet modification, weight control, exercise
Metformin
Sulphonylurea
Acarbose
DPP-4 Inhibitor #
Glitazone *
Insulin
# Authorised only as dual therapy with metformin or sulphonylurea where combination metformin and
sulphonylurea is contraindicated or not tolerated.
* Rosiglitazone is not authorised for triple therapy or for use with insulin.
This algorithm has been adapted from The NHMRC Blood Glucose Control guidelines.
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Oral Hypoglycaemics
Muscle
CHO
Thiazolidinediones
(Rosiglitazone,
Pioglitazone)
Glucose

Pancreas
β Sulphonylureas
(Gliclazide,
Glimepiride)
Liver
Glitinides
(Repaglinide)
Biguanides
(metformin)
Gut
Dipeptidyl peptidase-4 inhibitor
(DPP4)
Alpha-Glucosidase
(Sitagliptin)
Inhibitors (Acarbose)
Glucagon-like peptide-1
(GLP1) mimetic
(Exenatide)
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Metformin
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Metformin
Mechanism of action:
> reduces hepatic glucose production
> increases peripheral utilisation of glucose
in muscle and fat tissues (increases
sensitivity of insulin)
> decreases intestinal absorption of glucose
> decreases insulin requirements for
glucose disposal
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Metformin
> Well tolerated
> Side effects:
– Common:
• GI side effects, malabsorption of vitamin B12
– Infrequent:
• Rash
– Rare:
• Lactic acidosis, acute hepatitis
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2 years later ……
> Sue has a check up with her local GP.
> HbA1c was under 7.0mmol/L but now it is
8.3%.
> Currently taking Metformin 1.5g BD with
meals.
What now for Sue?
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What now for Sue?
Lifestyle modification
diet modification, weight control, exercise
Metformin
Sulphonylurea
Acarbose
DPP-4 Inhibitor #
Glitazone *
Insulin
# Authorised only as dual therapy with metformin or sulphonylurea where combination metformin and
sulphonylurea is contraindicated or not tolerated.
* Rosiglitazone is not authorised for triple therapy or for use with insulin.
This algorithm has been adapted from The NHMRC Blood Glucose Control guidelines.
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Sulphonylureas
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Sulphonylureas
Action
> Increase pancreatic insulin secretion.
> May improve insulin sensitivity in peripheral
tissue and decrease hepatic glucose output.
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Sulphonylureas and side effects
> Hypoglycaemia is the most frequent and
serious adverse effect.
> All patients are at risk, but especially:
– elderly
– renal impairment
– hepatic impairment
– those receiving interacting drugs.
16
5 years later
Sue has been going well with her HbA1c
usually under 7%. She has no diabetes
complications and her blood pressure and
cholesterol are controlled with medication. Over
the last 6 months her HbA1c has been steadily
rising and is now 7.9%. She is on maximum
Metformin and sulphonylurea.
What are her options now?
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What now for Sue?
Lifestyle modification
diet modification, weight control, exercise
Metformin
Sulphonylurea
Acarbose
DPP-4 Inhibitor #
Glitazone *
Insulin
# Authorised only as dual therapy with metformin or sulphonylurea where combination metformin and
sulphonylurea is contraindicated or not tolerated.
* Rosiglitazone is not authorised for triple therapy or for use with insulin.
This algorithm has been adapted from The NHMRC Blood Glucose Control guidelines.
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Diabetes medications
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Thiazolidinediones (‘Glitazones’)
> Drugs available:
– Rosiglitazone (Avandia®).
– Pioglitazone (Actos®).
> Mechanism of action:
– ↑ sensitivity of peripheral tissues to insulin.
– ↓ hepatic glucose output.
> Slow onset of action compared with other
antidiabetic agents.
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Thiazolidinediones – Side effects
> Less propensity for hypoglycaemia than
sulphonylureas.
– no direct insulin stimulation.
> Common:
– Peripheral oedema, weight gain, headache,
dizziness, arthralgia, decrease in haemoglobin &
haematocrit, increase in total and HDL cholesterol
(rosiglitazone).
> Infrequent:
– Distal limb fractures in females.
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DPP-4 Inhibitor - Sitagliptin
> Brand name: Sitagliptin (Januvia®).
> Action:
– slows breakdown of incretin hormone GLP-1.
• increase insulin synthesis and release
• decrease glucagon secretion → decreased hepatic
glucose production.
> Approved for dual therapy.
– When HbA1c >7% despite sulphonylurea or
metformin.
– When sulphonylurea and metformin combination
is contraindicated or not tolerated.
> Reduce the fasting and post prandial glucose.
> Reduce HbA1c by 0.5–0.8%
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DPP-4 Inhibitor – Sitagliptin
Side effects
> Common:
– Upper respiratory tract symptoms
– Headache
– Nausea
> Rare:
– Hypersensitivity reactions eg anaphylaxis,
angioedema
– Stevens-Johnson syndrome
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Useful resources
National Prescribing Service www.nps.org.au/consumers
References
> Colagiuri S, Dickinson S, Girgis S, and
Colagiuri R (2009) National evidence based
guideline for blood glucose control in type 2
diabetes. Diabetes Australia and NHMRC,
Canberra.
> Diabetes Outreach (2009), Diabetes Manual,
Edition 7, Section 10, Medications, Adelaide.
> National Prescribing Service (2008) Early use
of insulin and oral antidiabetic drugs. National
Prescribing Service Newsletter.
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