Recent advances in therapy of

diabetes

Dr. Sultan Bannat

 Type 1 diabetes
• In the past decade, two major advances have
improved the care of patients with type 1
diabetes.
• The relationship between metabolic control and
vascular complications; suboptimal blood glucose
control has a lasting harmful effect even if
control improves later.
• New forms of insulin (insulin analogues) and new
forms of delivery, as well as advances in glucose
monitoring.
 Intensive diabetes management
• Intensive management to minimize
hyperglycemia is now recommended for all
patients:
– More frequent administration of insulin
– Use of different insulin types
– More frequent blood glucose measurements and
changes to insulin dose than in conventional
therapy.
Intensive diabetes management
• Intensive schedules need to be individualized to suit
patient age and lifestyle:
– Adults and adolescents generally need intermediate-
acting insulin before bed for night-time control
– Some school-aged children need short-acting insulin at
afternoon rather than lunch-time to prevent late-
afternoon hyperglycemia
– many preschool-aged children can be managed with one
dose of intermediate-acting insulin in the morning and
small doses of rapid-acting insulin analogues to prevent
hyperglycemia later in the day.
– Insulin pumps may be useful for some patients with
frequent hypoglycemia or hypoglycemic unawareness.
Intensive diabetes management

• Intensive therapy is more demanding for patients and

their families, and adherence is obviously critical to
its success. Patient views are therefore central to
management decisions.
• An adolescent who struggles to comply with two
injections a day is unlikely to manage four injections.
• The demands of achieving good control are less than
the consequences of poor control.
• In adolescents, good control improves quality of life
and reduces the burden perceived by their parents
Intensive diabetes management

• The limiting factor preventing ideal glycemic control

remains hypoglycemia.
• Glucagon secretion is blunted early in the course of type 1
diabetes.
• The blood glucose threshold for release of catecholamines
is lowered in patients with better glycemic control, even
more so during sleep.
• Continuous glucose monitoring devices reveal the
frequency of nocturnal hypoglycemia and the limitations
of conventional blood glucose monitoring.
• Both the new insulin analogues and continuous
subcutaneous insulin therapy hold promise of improving
control without the risk of hypoglycemia
 Insulin analogues
• In the past, the pharmacokinetic
characteristics of insulin preparations have
been modified by mixing with substances
that delay absorption (eg, protamine and
zinc) and by varying crystal size.
• Recombinant DNA technology has now made
possible the creation of analogues of human
insulin with altered pharmacokinetic
characteristics .
 Rapid-acting analogues
• These are also known as rapid-onset and ultra-short-
acting insulins
– insulin aspart
– insulin lispro.
• They were created by modifying the amino acid sequence
of the insulin B chain.
• These analogues have the advantages that:
– they reduce postprandial hyperglycemia and between-meals
hypoglycemia
– their very rapid onset of action allows them to be injected
immediately before meals or even after eating.
• Their disadvantages are:
– could cause pre-prandial hyperglycemia.
 Long-acting analogues
• These were created by:
– substituting and adding amino acids to the insulin
molecule (glargine)
– by adding a fatty acid chain, which enhances binding to
albumin (detemir).
• The long-acting analogues have the advantages of:
– more reproducible absorption than conventional long-
acting insulins
– more predictable background control without the peaks
of action around lunchtime and during the night
– reduce the risk of nocturnal hypoglycemia and produce a
modest reduction in fasting blood glucose levels
• Better night-time blood glucose control with pump therapy.
 New use of old drugs
• Adding metformin to the treatment regimen for
type 1 diabetes can improve metabolic control
by reducing insulin resistance, a problem in both
obese patients and adolescents with diabetes, in
whom the physiological insulin resistance of
puberty is exaggerated, necessitating high
insulin doses.
• Metformin is suitable only for patients with
normal renal and hepatic function who remain
compliant with insulin therapy.
 New delivery systems
Pump therapy
• Pump therapy has been reintroduced with improved technology.
• Small amounts of a rapid-acting insulin analogue are infused at a
basal rate with extra boluses for each meal and snack.
• The major advantages are less variable absorption and improved
insulin pharmacokinetics and varying the basal rate can help
regulate overnight blood glucose levels.
• Pump therapy is suitable for motivated patients, particularly those
with frequent hypoglycemic episodes or hypoglycemic
unawareness.
• Mechanical interruption of the pump can rapidly lead to ketosis,
which is of particular concern in pregnancy.
• Pump therapy must therefore be accompanied by frequent blood
glucose monitoring.
 New delivery systems
Aerosols
• Aerosolised insulins for delivery by inhalation are under active
investigation, with Phase III studies completed.
• These insulins provide effective cover for meals in combination with
once-daily, long-acting, subcutaneous insulin.
• However, aerosol delivery requires six times as much insulin for the
same effective dose as subcutaneous injection, which may create a cost
barrier to widespread use.
• Also, the long-term safety of delivering large amounts of insulin to the
alveolae is not known.
• At present, all systems deliver insulin to the systemic circulation rather
than the enteroportal circulation. Systemic delivery contributes to the
insulin resistance associated with obesity and adolescence and is a
major barrier to physiological insulin replacement.
• However, a method of accessing the enteroportal circulation is not
currently in sight.
 New monitoring systems
Continuous blood glucose monitoring
• Intermittent measurements of capillary blood glucose give a
limited glimpse of blood glucose levels, which may fluctuate
widely over 24 hours.
• Continuous monitoring reveals postprandial fluctuations in
glucose level and asymptomatic nocturnal hypoglycemia, and is
likely to be especially useful in programming overnight basal
insulin rates for pump therapy.
• Continuous monitoring systems measure interstitial blood glucose
via an indwelling cannula in the abdomen or buttocks.
• However, they are expensive and, at present, are most applicable
for use by diabetes centres which lend devices to patients for
restabilisation.
• Devices under investigation have alarms to alert patients to
glucose levels outside a target range and provide immediate read-
outs.
 New monitoring systems
Non-invasive blood glucose monitoring
• Frequent automatic glucose readings can be
obtained non-invasively through the process of
reverse iontophoresis, in which a low electric
current pulls glucose molecules through the skin
for collection in a gel disc.
• A device that is worn like a wristwatch is
approved for patients aged over 7 years in the
United States, but its cost (about US$1000 for the
device and more than US$100 per disposable 12-
hour sensor) limits more widespread use.
 Type 2 diabetes
• Type 2 diabetes mellitus generally forms part of
the “metabolic syndrome”:
– insulin resistance,
– obesity and
– a range of cardiovascular risk factors.
• Advances in management of type 2 diabetes
include recognition of the need for early and
aggressive management of:
– insulin resistance and
– associated abnormalities, such as dyslipidemia,
hypertension and albuminuria.
 Increase insulin sensitivity
• The aim should be to target insulin resistance with diet
and exercise plus metformin therapy. A weight loss of 5 kg
leads to a 25%–50% reduction in insulin resistance.
• Metformin is tolerated by most patients if started at a low
dose (eg, 250–500 mg/day), which is slowly increased
depending on blood sugar response and tolerance.
• The thiazolidinediones (rosiglitazone and pioglitazone) are
newer insulin-sensitising agents which are effective, but
have the disadvantage of causing some weight gain and
fluid retention.
• However, unlike metformin, they are safe in patients with
renal impairment.
 Increase circulating insulin
• The next step is to increase circulating insulin level.
• Oral agents currently available for this purpose are:
– the sulfonylureas and
– the newer glitinides.
• As sulfonylureas are potent and long-acting
• hypoglycemia is a significant clinical problem, but can be
avoided with careful dose titration.
• Sulfonylureas cause weight gain in most patients and lose
efficacy with time
• Other than half-life differences, there is little to distinguish
later-generation sulfonylureas.
• Metformin should be continued if the patient is obese.
Increase circulating insulin

• Glitinides (eg, repaglinide) are short-acting

drugs that increase insulin secretion.
• They are well tolerated but less potent in
clinical practice than the sulfonylureas.
• Their advantage lies in their short half-life,
making hypoglycemia less common, but pre-
meal dosing is a disadvantage for many
patients.
 Exogenous insulin

• If diabetic control remains, or becomes, suboptimal

when taking oral combination therapy with
metformin and a sulfonylurea, then insulin is
indicated.
• Because of the benefits of good diabetic control,
delay in introducing insulin in these patients is now
considered unacceptable
 Exogenous insulin

• Insulin is usually necessary because of natural

progression of the disease and not because of
any “failure” on patients’ part
• Introduce the concept well in advance, and that
insulin often substantially improves how
patients feel.
• With currently technologies, it is straightforward
to develop an acceptable “physiological” insulin-
replacement regimen for almost all patients.
 Insulin Analogues
• Newer analogue insulins (including mixtures) have a
definite place in the management of type 2 diabetes
and contribute to the excellent choices available.
• There is little point in continuing sulfonylurea or
glitinide therapy after introducing insulin.
• Advantages of ceasing oral agents are:
– simplification of therapy,
– less chance of drug interaction,
– reduced costs and
– improved compliance.
• However, metformin should be continued in obese
patients, as it helps maintain weight and allows lower
insulin doses to be used.
 Insulin secretagogues
• Historically, hyperglycemia in diabetes has
been viewed as a failure of insulin-mediated
glucose disposal into muscle and adipose
tissue
This looks to be an over simplification of a
more complicated issue
• Two other factors:
– Glucagon
– Gastric emptying
 Insulin secretagogues
Incretins
• Hormones produced by the gastrointestinal
tract in response to incoming nutrients, and
have important actions that contribute to
glucose homeostasis.
• Two hormones:
– Gastric inhibitory polypeptide (GIP)
– Glucagon-like peptide-1 (GLP-1).
 What are incretins?
Gastric Inhibitory Polypeptide (GIP)
• Secreted by the K cells of the proximal gut.
However, type 2 diabetes patients are
resistant to its action (high blood level),
making it a less attractive therapeutic target.
 What are incretins?
Glucagon-like peptide-1 (GLP-1)
• a 30-amino acid peptide secreted in response
to the oral ingestion of nutrients by L cells,
primarily in the ileum and colon.
• There are GLP-1 receptors in islet cells and in
the central nervous system, among other
places.
• GLP-1 is metabolized by the enzyme
dipeptidyl peptidase-IV (DPP-IV) .
 Glucagon-like peptide-1 (GLP-1)

• It enhances glucose-dependent insulin

secretion.
• Inhibits glucagon secretion and therefore
hepatic glucose production.
• Slows gastric emptying.
• Increases satiety resulting in less food intake.
• Appears to stimulate insulin gene
transcription and insulin synthesis.
 Glucagon-like peptide-1 (GLP-1)

• In animal studies it increases beta-cell mass

by:
- Decreasing beta cell apoptosis.
- Stimulating the growth of new beta cells.
???... Long term benefit in reversing the
progressive insulin deficiency.
 Glucagon-like peptide-1 (GLP-1)

• As glucose levels approach the normal range,

the GLP-1 effects on insulin stimulation and
glucagon inhibition declined (glucose
dependence - reduction of hypoglycemia. -
therapeutic advantage)
• Unfortunately, GLP-1 is rapidly broken down
by the DPP-IV enzyme (very short half-life in
plasma - requires continuous IV infusion).
 Glucagon-like peptide-1 (GLP-1)
Two options:
• Incretin mimetics are glucagon-like peptide-1
(GLP-1) agonists.
• Dipeptidyl peptidase-IV (DPP-IV) antagonists
inhibit the breakdown of GLP-1
 Incretin mimetics

• Exenatide
• Liraglutide
• Long acting exenatide
• Progressive weight loss continuing for 82
weeks. Patients convenience
• Nausea &vomiting, more frequent at the
initiation of treatment
 Dipeptidyl Peptidase-IV Antagonists

• The concept is to allow the endogenous GLP-

1 to remain in circulation for a longer period.
• DPP-IV inhibitors are oral, rather than
injectable.
• Weight neutral.
• associated with a low incidence of
hypoglycemia or gastrointestinal side effects.
• Preliminary long-term studies suggest a
durable effect on glycemia and improvement
in some parameters of beta-cell function.
 Dipeptidyl Peptidase-IV Antagonists
(DPP 4 inhibitors)
• Sitagliptin and vildagliptin are the first agents
in this class to have received FDA approval.
• Incidence of adverse reactions was reported
to be very low in a pooled safety data from
5141 patients.
• They are indicated as monotherapy and in
combination with metformin,
thiazolidinediones and insulin.
• They look to be at least weight neutral.
 Drugs on the horizon
• Dual PPARγ/α agonists: The nuclear hormone
receptor PPARγ (peroxisome proliferators-
activated receptor) is involved in glucose and, to
a lesser extent, lipid metabolism and is a target
of the thiazolidinediones (glitizones). Drugs are
currently under trial which act both on this
receptor and a related receptor involved in lipid
metabolism, which is targeted by the fibrates.
These dual PPARγ/a agonists will probably have
an important role in managing type 2 diabetes
and the metabolic syndrome within a few years.
 Orlistat
• This lipase inhibitor is currently indicated for
use in obesity. Clinical trials have
demonstrated its usefulness as an insulin
sensitizing agent, with the added benefit of
weight management. Overall efficacy
appears similar to that of metformin or
sulfonylurea
 Monitoring of diabetes
HbA1c measurement
• Measurement of (HbA1c) remains the criterion
standard to judge the outcome of diabetes
management.
• Rapid measurement with a desktop device expedites
assessment and education.
• accurate prediction of the risk of vascular
complications for a given HbA1c level can be done.
• Reducing the HbA1c level from 9% to 8% and
maintaining the reduction reduces the risk of
proliferative and severe non-proliferative retinopathy
by 70%–80%.
HbA1c measurement
• It is noteworthy that 1–2 days of hyper-glycaemia (eg,
during an infection) will increase HbA1c level for
some weeks.
• HbA1c level is falsely low in some
hemoglobinopathies and in states of increased red
cell turnover, such as hemolysis.
• In these cases, the level of fructosamine (glycosylated
albumin) can be measured.
• This reflects glycemic control over weeks, rather than
the 2–3 months reflected by HbA1c level. Its assay is
less reliable, and it is not indicated routinely.
New units for HbA1c measurement
• A new type of measurement is being introduced for
measuring HbA1c: the HbA1c will be recorded in
mmol/mol instead of %.
Current HbA1c (%) New HbA1c (mmol/mol)
4 20
5 31
6 42
6.5 48
7 53
7.5 58
8 64
9 75
10 86
Target HbA1c

• On Hypoglycemic Agents
– 6.5% (48 mmol/mol) – 7.0% (53 mmol/mol) with
no severe hypoglycemia
• On Insulin therapy
– < 7.0% (<53 mmol/mol) with no severe
hypoglycemia
• This is a guide only, as patients individual
circumstances need to be taken into
consideration, (elderly, living alone,
dementia, co-existing morbidities)
Frequency of HbA1c testing

• Test HbA1c 3 months after change in dose or

addition of new hypoglycemic agent
• If patient is stable and HBA1c is in target
then test every 6 months
• Do not test more than 3 monthly
Home blood glucose monitoring

• It is crucial for diabetic control.

• In type 2 diabetes, insulin resistance makes
good control of postprandial blood sugar
very difficult.
• It is recommended that fasting blood glucose
be recorded at least twice daily at different
times (before meals and before bed) during
the week so that patterns of glucose control
can be identified.
• Blood glucose lowering drugs:
approach to initiation of therapy in
type 2 diabetes
 Type 2 DM – BMI (18.5 - 27 kg/m²)
• Asymptomatic new T2 patient,
• no weight loss, no ketones
• Commence on Metformin 500mg bd
• Titrate Metformin to maximum dose (1g bd) if HbA1c
> 7.0 % (> 53 mmol/mol)
• Add in Sulphonylurea once daily if HbA1c remains >
7.0 % (> 53 mmol/mol)
(Titrate dose to maximum dose, to achieve target)
• For example: start Gliclazide MR 30mg once daily
max dose is 120mg once daily (diamicron)
• If HbA1c remains > 7.0 % (>53 mmol/mol) Contact
Diabetes Centre
 Type 2 DM –BMI (18.5 - 27 kg/m²)
• Symptomatic, weight loss, ketones may be present
• Commence on Sulphonylurea once daily.
• Titrate dose of Sulphonylurea to maximum dose if blood
glucose remains elevated
• HbA1c > 7.0% (> 53 mmol/mol)
- Further weight loss or ketones present suggests need for
insulin therapy
• - Refer to Diabetes Day Centre urgently.
• HbA1c > 7.0% (> 53 mmol/mol)
• - Weight stable, no ketones
• - Commence Metformin and titrate to maximum dose.
• If HbA1c remains > 7.0 %(> 53 mmol/mol) on maximum oral
agents - will need to commence insulin therapy
• Refer to Diabetes Day Centre
 Overweight T2 DM BMI > 27 – 30 kg/m²
• Commence on Metformin 500mg bd
• Increase Metformin to maximum dose (1g bd) if
HbA1c > 7.0% (>53 mmol/mol)
• If HbA1c remains > 7.0 % (> 53 mmol/mol) will need a
second glucose lowering agent
• Option 1
• Sulphonylurea
• Option 2
• DPP- 4 Inhibitor
• The TZD Pioglitazone could also be used in this setting
• Liaise with Diabetes Centre for advice
 Overweight T2DM BMI > 27 – 30 kg/m²

• Treatment Option 1 in combination with Metformin

• Add Sulphonylurea
• Titrate dose of Sulphonylurea to maximum dose if
HbA1c remains > 7.0% (> 53 mmol/mol)
• Assess patient for signs and symptoms of
hypoglycemia
• Failure to achieve target Hba1c with Metformin in
combination with
• Sulphonylurea – Contact Diabetes Centre
 Overweight T2DM BMI > 27 – 30 kg/m²
• Treatment Option 2 in combination with Metformin
• DPP-4 Inhibitor
– Janumet (1gm/50mg bd – Metformin + Sitagliptin) or
– Eucreas (1gm/50mg bd – Metformin + Vildagliptin) or
– Onglyza (Saxagliptin 5mg once daily)
• Failure to achieve target Hba1c with Metformin in
combination with DPP 4 Inhibitor – Add in
Sulphonylurea
• Titrate dose of Sulphonylurea to maximum dose if
HbA1c remains > 7.0 % (> 53 mmol/mol)
• Failure to achieve target Hba1c with Metformin +
DPP-4 Inhibitor in combination with Sulphonylurea –
Contact Diabetes Centre
 Obese T2DM BMI > 30 – 35kg/m²
• Commence on Metformin 500mg bd
• Increase Metformin to maximum dose (1g bd) if HbA1c >
7.0 % (> 53 mmol/mol)
• If HbA1c remains > 7.0 % (> 53 mmol/mol) will need a
second glucose lowering agent
• Treatment Option 1 in combination with Metformin
• Add Sulphonylurea
• Titrate dose of Sulphonylurea to maximum dose if HbA1c
• > 7.0 % (> 53mmol/mol)
• Assess patient for signs and symptoms of hypoglycemia
• Failure to achieve target Hba1c with Metformin in
combination with Sulphonylurea
• Contact Diabetes Centre or Community Diabetes Nurse for
advice
 Obese T2DM BMI > 30 - 35 kg/m²
• Treatment Option 2 in combination with
Metformin
• DPP-4 Inhibitor
– Janumet (1gm/50mg bd – Metformin + Sitagliptin) or
– Eucreas (1gm/50mg bd – Metformin + Vildagliptin) or
– Onglyza (Saxagliptin 5mg once daily)
• Failure to achieve target Hba1c with Metformin
in combination with DPP-4
• - Add in Sulphonylurea (continue DPP-4) or GLP
1 injection (stop DPP 4).
• Contact Diabetes Centre for advice
 Obese T2DM BMI > 30 - 35 kg/m²

• Treatment Option 3 in combination with

Metformin
• GLP – 1 Injection
• Exenatide BD Injection or Liraglutide OD
Injection
• Failure to achieve target Hba1c with Metformin
in combination with GLP-1 injection
• Add in Sulphonylurea
• Contact Diabetes Centre for advice
 Obese T2DM BMI > 35kg/m²
• Commence on Metformin 500mg bd
• Increase Metformin to maximum dose (1g
BD) if HbA1c > 7.0 % (> 53 mmol/mol)
• If HbA1c remains > 7.0 % (> 53 mmol/mol)
will need a second glucose lowering agent
• Option 1 GLP-1 injection (preferred option)
• Option 2 DPP-4 Inhibitor
• Option 3 Sulphonylurea
• The TZD Pioglitazone could also be used in
this setting
• Individual drug profiles
 Metformin
Advantages
• Effective
• Promotes weight loss
• No hypoglycemia
• Long term data
Disadvantages
• Nausea, flatulence, diarrhea – titrate slowly
• Cannot be used in renal impairment (i.e. Creatinine _ 130
umol/L) – risk of Lactic Acidosis
• Can cause B12 deficiency
Maximum dose is typically 1gm twice daily
Give dose with food – breakfast and evening meal
 Sulphonylurea
Advantages
•Effective
•Long term data
Disadvantages
• Hypoglycemia
• Weight gain
• ? Accelerate beta cell failure
• Caution in patients with hepatic cirrhosis and renal
impairment – increased risk of hypoglycemia
Patient must be educated on the risk and management of
Hypoglycemia
Medications in this class include: Gliclazide MR (Diamicron) and
Glimepiride (Amaryl)
 DPP 4 Inhibitors
Advantages
• Weight neutral
• No increased risk of hypoglycemia
• May preserve pancreatic beta cell function (speculation
currently)
Disadvantages
• Side effects nausea, abdominal bloating, diarrhea
• No long-term safety data
Medications in this class include:
Sitagliptin 50mg bd (in combination with Metformin =
Janumet)
Vildagliptin 50mg bd (in combination with Metformin =
Eucreas)
Saxagliptin 5mg once daily
 GLP 1 Agonist/Injection
Advantages
• Weight loss
• No hypoglycemia when used on its own
• Reduces postprandial hyperglycemia
• Delays gastric emptying
• May preserve pancreatic beta cell function (speculation currently)
Disadvantages
• Nausea, bloating, diarrhea
• Subcutaneous injection
• Pancreatitis (rare)
• No long-term safety data
• In combination with Sulphonylurea, may need to reduce the dose of
Sulphonylurea to prevent hypoglycemia
Medications in this class include:
Exenatide BD S/C injection, Liraglutide OD S/C injection
 PIOGLITAZONE
(Thiazolidenedione or TZD)
Advantages
• No hypoglycemia
• Insulin sensitizer
• Some data suggests cardiovascular benefit
• Preserve beta cell function
Disadvantages
• Weight gain
• Fluid overload NOT TO BE USED IN HEART FAILURE
• Increased risk of bone fracture – avoid in patients with
metabolic bone disease
• Drop in haemoglobin
Starting dose is 15mg once daily, increased to 45mg a day
Can be used in combination with Metformin or Sulphonylurea or
insulin or DPP-4
 Lipids in T2DM
• Check fasting lipids 3 months after starting
therapy or after change in dose
• Once on stable dose check fasting lipid
profile every 6 months
 Lipid-Lowering (1)
• no previous vascular event
• Targets: LDL cholesterol < 2.6mmol/L
• HDL > 1.0mmol/l in men, >1.1mmol/L in women
• Triglycerides <1.7mmol/L
• LDL cholesterol above target
• Start statin: Atorvastatin 10mg* od or
• Rosuvastatin 10mg* od or
• Simvastatin 10mg* od or
• Pravastatin 10mg od
• Give at bed-time
• Precaution: Renal failure
• Liver failure (LFT > 3 times the upper limit of normal-caution)
• Previous hx of myositis (avoid statins)
• Previous reaction to statin therapy
• Teratogenic
• *Caution with Warfarin
 Lipid Lowering (2)
• no previous vascular event
• LDL cholesterol remains above target
• Increase statin dose: Atorvastatin to max dose of 80mg od
• Rosuvastatin to max dose of 40mg od
• Simvastatin to max dose of 80mg od
• Pravastatin to max dose of 40mg od
• Fail to achieve LDL cholesterol despite max dose
• Try different statin agent (e.g. Atorvastatin more potent than
Pravastatin)
• Reaction to Statin therapy
• Documented myositis: avoid statins
• Acute deterioration in liver function: avoid statin
• Non-specific symptoms: trial of another statin preparation
• Repeat fasting lipid profile 3 months after starting therapy.
• Once stable check lipid profile 6 monthly
• If patient has a history of renal or liver dysfunction monitor CK and
LFT
 Lipid Lowering (3)

• (no previous vascular event)

• Baseline LDL cholesterol < 2.6 mmol/L on no
treatment
• If more than one CV risk factor other than
diabetes.
• Start low dose statin
• Aim for reduction of > 30% from baseline LDL
cholesterol
• Lipid-Lowering in patients who have had a
previous vascular event.
• Target LDL cholesterol < 1.8mmol/L
• All patients should be on a statin no matter
what their LDL cholesterol is
• Adjust therapy as per previous slide to
achieve target LDL <1.8mmol/L
 Anti-Platelet Agent
• Patients with a previous vascular event – should be on an anti-platelet
agent
Aspirin 75mg daily or
Clopidogrel 75 mg daily
• Patients with no history of a previous vascular event but have one or
more of the following – should be on an anti-platelet agent
– Microalbuminuria
– Smoker
– Asymptomatic carotid artery disease (stenosis >30%)
– Atrial fibrillation (consider Warfarin)
– Peripheral arterial disease
– Angina
– Abnormal 12-lead ECG
Patients with no history of a previous vascular event – do not necessarily
need to be on an anti-platelet agent
The usual contraindications to Aspirin and Clopidogrel therapy apply