2012 SEMDSA Guideline for type 2 diabetes mellitus

Report
2012 SEMDSA Guideline for the
Management of Type 2 Diabetes
Mellitus
Aslam Amod
1st FCPSA Congress
19 May 2012, Cape Town
Amod A et al. The 2012 SEMDSA guideline for the management of
type 2 diabetes. JEMDSA. 2012;17(1):S1-S94.
Available at http://www.jemdsa.co.za
The Guideline & Steering Committee
Chairperson: Aslam Amod
Section 1
Definition, diagnosis and organisation
Ayesha A Motala
Definition, classification, diagnosis and
screening
Naomi S Levitt
Organisation of Diabetes Care
Section 2
Lifestyle Modification
Jeannie Berg, Madelein
Young, Natalie Grobler
Diabetes self management education,
Medical nutrition therapy
Andrew Heilbrunn
Physical activity and type 2 diabetes
The Guideline & Steering Committee (2)
Chairperson: Aslam Amod
Section 3
Glycaemic Control
Larry A Distiller
Assessment of Glycaemic Control
Aslam Amod, Fraser
Pirie, Joel Dave
Glycaemic control: Non-insulin therapies
Insulin-based therapies
The SEMDSA 2012 algorithm
Ken Huddle
Hypoglycaemia, Diabetes in pregnancy
Daksha Jivan
Hyperglycaemic emergencies
Imran Paruk
In-hospital management of type 2 diabetes
The Guideline & Steering Committee (3)
Chairperson: Aslam Amod
Section 4
Complications and co-morbidities
Wayne May
Obesity in type 2 diabetes
Derick Raal, Dirk Blom
Cardiovascular risk and dyslipidaemia
Brynne Ascott-Evans
Aspirin therapy
Susan Brown
Hypertension
Willie Mollenze
Chronic kidney disease and Retinopathy
Paul Rheeder, Lynne
Tudhope, Gerda van
Rensburg
Neuropathy and foot problems in type 2
diabetes
The Guideline & Steering Committee (4)
Chairperson: Aslam Amod
Section 5
Diabetes in Special Circumstances
Yasmin Ganie, Michelle
Carrihill
Type 2 diabetes in children and adolescents,
management of sick days
Sophie Rauff
Type 2 diabetes in older persons
Danie van Zyl
Type 2 diabetes in high risk ethnic groups
Hoosen Randeree
Type 2 diabetes during Ramadaan
Duma Khutsoane
Type 2 diabetes in HIV infected individuals
Pankaj Joshi
Prevention/Delay of Type 2 Diabetes
Peter Raubenheimer
Diabetes and driving
The Advisory Committee
SEMDSA / Association of
Clinical Endocrinologists
(ACE-SA) Members
Philip Erasmus, Gregory Arthur Hough, Stanley
Landau, Puvanesveri Naiker, MAK Omar,
Helena Oosthuizen, William Toet, Carsten
Weinreich, Holger Wellmann
Department of Health
(Chronic Diseases)
Anne Croasdale , Melvyn Freeman, Sandhya
Singh
Society of General /
Family Practitioners,
Angelique Coetzee, Philip Erasmus
Diabetes Education
Society of South Africa
(DESSA)
Jeannie Berg, Gerda van Rensburg, Madelein
Young
Diabetes South Africa
(DSA)
Medical Aids
Council of Medical
Schemes (CMS)
Leigh-Ann Bailie , Ranga Kuni
Margaret Campbell (Discovery)
Selaelo Mametja
Introduction
• Target Audience
– All healthcare professionals (medical & allied)
– Focus on primary care, but also general
physician
– Funders of healthcare
– Undergraduates and postgraduates
• Not for “experts”
– Self-proclaimed or otherwise
• Disclaimer
International Diabetes Federation. IDF Diabetes Atlas [cited 2012 Mar 18]. Available from:
http:// www.idf.org/diabetesatlas
Disclaimer
•
This guideline is not intended to replace professional judgement,
experience and appropriate referral.
•
These guidelines are intended to inform general patterns of care, to
enhance diabetes prevention efforts and to reduce the burden of
diabetes complications in people living with this disease.
•
They reflect the best available evidence at the time, and
practitioners are encouraged to keep updated with the latest
information in this rapidly changing field.
•
While every care has been taken to ensure accuracy, reference to
product information is recommended before prescribing.
•
SEMDSA assumes no responsibility for personal or other injury, loss or
damage that may result from the information in this publication.
•
Unless otherwise specified, these guidelines pertain to the care of
adults with type 2 diabetes at primary care level.
Epidemiology / Prevalence
• Type 2 > 90%
– Local studies using 1985 WHO criteria
• Rural African: 3.5%
• Urban Coloured: 10.8%
• Urban Indian: 13%
• 30-85% undiagnosed
– >90% are obese
• IDF Atlas 5th edition
• 6.5% of adults aged 20-79 years
International Diabetes Federation. IDF Diabetes Atlas [cited 2012 Mar 18]. Available from:
http:// www.idf.org/diabetesatlas
Diagnosis and screening
Diagnosis (WHO criteria)
Diagnostic test
IFG
IGT
Diabetes
Fasting plasma glucose (FPG) a
Two-hour plasma glucose (2-h
PG) during oral glucose
tolerance test (OGTT)b
Glycated haemoglobin A1c
(HbA1c) c
Random plasma glucose (RPG) d
World Health Organization. Definition and diagnosis of diabetes mellitus and intermediate hyperglycaemia
[cited 2011 Sep 20]. Available from: http://whqlibdoc.who.int/publications/2006/9241594934_eng.pdf.
Diagnosis (WHO criteria)
Diagnostic test
IFG
Fasting plasma glucose (FPG) a
6.1 to 6.9
mmol/L
Two-hour plasma glucose (2-h
PG) during oral glucose
tolerance test (OGTT)b
<7.8 mmol/L
(if
measured)
Glycated haemoglobin A1c
(HbA1c) c
-
Random plasma glucose (RPG) d
Diagnosis (WHO criteria)
Diagnostic test
IGT
Fasting plasma glucose (FPG) a
<7.0mmol/L
(if measured)
Two-hour plasma glucose (2-h
PG) during oral glucose
tolerance test (OGTT)b
7.8 to 11.0
mmol/L
Glycated haemoglobin A1c
(HbA1c) c
-
Random plasma glucose (RPG) d
Diagnosis (WHO criteria)
Diagnostic test
Diabetes
Fasting plasma glucose (FPG) a
> 7.0 mmol/l, or
Two-hour plasma glucose (2-h
PG) during oral glucose
tolerance test (OGTT)b
> 11.1 mmol/l, or
Glycated haemoglobin A1c
(HbA1c) c
Random plasma glucose (RPG) d
> 6.5%, or
≥ 11.1 mmol/l if
classic symptoms
or hyperglycaemic
crisis is present
Diagnosis (WHO criteria)
Diagnostic test
IFG
IGT
Diabetes
Fasting plasma glucose (FPG) a
6.1 to 6.9
mmol/L
<7.0mmol/L
(if measured)
> 7.0 mmol/l, or
Two-hour plasma glucose (2-h
PG) during oral glucose
tolerance test (OGTT)b
<7.8 mmol/L
(if
measured)
7.8 to 11.0
mmol/L
> 11.1 mmol/l, or
-
-
> 6.5%, or
-
≥ 11.1 mmol/l if
classic symptoms
or hyperglycaemic
crisis is present
Glycated haemoglobin A1c
(HbA1c) c
Random plasma glucose (RPG) d
-
Diagnosis (WHO criteria)
Diagnostic test
IFG
IGT
Diabetes
Fasting plasma glucose (FPG) a
6.1 to 6.9
mmol/L
<7.0mmol/L
(if measured)
> 7.0 mmol/l, or
Two-hour plasma glucose (2-h
PG) during oral glucose
tolerance test (OGTT)b
<7.8 mmol/L
(if
measured)
7.8 to 11.0
mmol/L
> 11.1 mmol/l, or
-
-
> 6.5%, or
-
≥ 11.1 mmol/l if
classic symptoms
or hyperglycaemic
crisis is present
Glycated haemoglobin A1c
(HbA1c) c
Random plasma glucose (RPG) d
-
For clinical purposes, the diagnosis of diabetes should always be
confirmed by repeating the test on another day (preferably the same
test), unless there is unequivocal hyperglycaemia with acute metabolic
decompensation or obvious symptoms (polyuria, polydipsia and weight
loss).
Diagnosis (WHO criteria)
Diagnostic test
IFG
IGT
Diabetes
Fasting plasma glucose (FPG) a
6.1 to 6.9
mmol/L
<7.0mmol/L
(if measured)
> 7.0 mmol/l, or
Two-hour plasma glucose (2-h
PG) during oral glucose
tolerance test (OGTT)b
<7.8 mmol/L
(if
measured)
7.8 to 11.0
mmol/L
> 11.1 mmol/l, or
-
-
> 6.5%, or
-
≥ 11.1 mmol/l if
classic symptoms
or hyperglycaemic
crisis is present
Glycated haemoglobin A1c
(HbA1c) c
Random plasma glucose (RPG) d
-
“Fasting” is defined as no caloric intake for at least eight hours
b The test should be performed as described by the WHO, using a
glucose load containing the equivalent of 75 g anhydrous glucose
dissolved in 250 ml water ingested over five minutes
a
Diagnosis (WHO criteria)
Diagnostic test
IFG
IGT
Diabetes
Fasting plasma glucose (FPG) a
6.1 to 6.9
mmol/L
<7.0mmol/L
(if measured)
> 7.0 mmol/l, or
Two-hour plasma glucose (2-h
PG) during oral glucose
tolerance test (OGTT)b
<7.8 mmol/L
(if
measured)
7.8 to 11.0
mmol/L
> 11.1 mmol/l, or
-
-
> 6.5%, or
-
≥ 11.1 mmol/l if
classic symptoms
or hyperglycaemic
crisis is present
Glycated haemoglobin A1c
(HbA1c) c
Random plasma glucose (RPG) d
-
The classic symptoms of hyperglycaemia include polyuria, polydipsia
and weight loss.
“Hyperglycaemic crisis” refers to diabetic ketoacidosis or hyperosmolar
nonketotic hyperglycaemia.
d
Diagnosis (WHO criteria)
Diagnostic test
IFG
IGT
Diabetes
Fasting plasma glucose (FPG) a
6.1 to 6.9
mmol/L
<7.0mmol/L
(if measured)
> 7.0 mmol/l, or
Two-hour plasma glucose (2-h
PG) during oral glucose
tolerance test (OGTT)b
<7.8 mmol/L
(if
measured)
7.8 to 11.0
mmol/L
> 11.1 mmol/l, or
-
-
> 6.5%, or
-
≥ 11.1 mmol/l if
classic symptoms
or hyperglycaemic
crisis is present
Glycated haemoglobin A1c
(HbA1c) c
Random plasma glucose (RPG) d
c Provided that:
-
-The test method meets stringent quality assurance criteria
-The assay is NGSP certified and standardised to the DCCT assay
-There are no conditions present which preclude its accurate
measurement
Use of HbA1c in the diagnosis of diabetes
mellitus
For the diagnosis of
diabetes
HbA1c > 6.5%
HbA1c < 6.5% does not exclude diagnosis
by blood glucose
Glucose–based tests (FPG, OGTT) are still
valid
Interpretation of HbA1c < No recommendation, because of
6.5%
insufficient evidence
Use of HbA1c in the diagnosis of diabetes
mellitus
Requirements to fulfill
(provisos) for use of
HbA1c for diagnosis
Stringent quality assurance tests in placea
Assays standardised to criteria aligned
with international reference valuesb
Low cost and wide availability
No conditions present which preclude
accurate measurement
a Appropriate
conditions for assay method: Standardised assay, low
coefficient of variability, and calibrated against International Federation
of Clinical Chemists (IFCC) standards
b DCCT aligned and NGSP certified
Use of HbA1c in the diagnosis of
diabetes mellitus
Choice between HbA1c Cost
and plasma glucose
Availability of equipment
should be based on
local considerations
National quality-assurance system
Population characteristics (e.g.
prevalence of malaria or
haemoglobinopathies)
Crucial to ensure that accurate blood
glucose measurement be generally
available at primary healthcare level
before introducing HbA1c measurement
as a diagnostic tool
Factors which influence HbA1c
measurement
Increased HbA1c: Iron deficiency, vitamin B12 deficiency,
decreased erythropoiesis
Erythropoiesis
Decreased HbA1c: Administration of erythropoietin, iron or vitamin
B12, reticulocytosis, chronic liver disease
Genetic or chemical alterations in haemoglobin may increase or
Altered
haemoglobin decrease HbA1c: Haemoglobinopathies, HbF, methaemoglobin
Increased HbA1c: Alcoholism, chronic renal failure
Glycation
Decreased HbA1c: Aspirin, vitamins C and E, certain
haemoglobinopathies, increased intra-erythrocyte pH
Increased HbA1c with increased erythrocyte life span: Splenectomy
Decreased HbA1c with decreased erythrocyte life span:
Erythrocyte
Haemoglobinopathies, splenomegaly, rheumatoid arthritis, drugs
destruction
(e.g. antiretrovirals, ribavirin, dapsone)
Increased HbA1c: Hyperbilirubinaemia, carbamylated
haemoglobin, alcoholism, large doses of aspirin, chronic opiate use
Assays
Decreased HbA1c: Hypertriglyceridaemia
Variable HbA1c: Haemoglobinopathies
Note: Some of these factors cannot be detected by certain assays
Screening
• Diagnosis vs. screening
• Targeted screening advocated
– High rate of undiagnosed diabetes
– Age > 45 or any age with multiple risk factors
– Repeat every 3 yrs or more frequently
– Use FPG, OGTT or HbA1C
• Exclude diabetes
– FPG < 5.6 mmol/L; if not do OGTT
– RPG < 5.6 mmol/L; if not do FPG or OGTT
– HbA1C – do OGTT if 6.0 to 6.4%
Random PG
<5.6
mmol/L
5.6 – 11.0
mmol/L
≥ 11.1 mmol/L
+ Symptoms
Diabetes
excluded
Inconclusive
Do FPG or OGTT
Diabetes
Fasting PG
<5.6
mmol/L
5.6 – 5.9
mmol/L
6.0 – 6.9
mmol/L
≥ 7.0
mmol/L
Diabetes
excluded
Inconclusive
Do OGTT
IFG
(Repeat)
Diabetes
(Repeat)
HbA1C
Normal
Normal – 5.9
%
6.0 – 6.4
%
≥ 6.5
%
Diabetes
excluded
Clinical
judgement
Inconclusive
Do FPG/OGTT
Diabetes
(Repeat)
2hr OGTT
< 7.8
mmol/L
7.8 – 11.0
mmol/L
≥ 11.1 mmol/L
Diabetes
excluded
IGT
(Repeat)
Diabetes
(Repeat)
Glycaemic targets
Individualised glycaemic targets
Patient type
Young
Newly diagnosed
No cardiovascular
disease
Low CV risk
Target HbA1c
Target FPG
Target PPG
< 6.5%
4.0 - 7.0
mmol/l
4.4 - 7.8
mmo/l
Majority of patients
< 7%
4.0 - 7.0
mmol/l
5.0 -10.0
mmol/l
< 7.5%
(< 8.0%)
5.0 - 8.0
mmol/l
< 12.0
mmol/l
Elderly
Hypoglycaemic unaware
Poor short-term prognosis
Established CV disease
High CV risk
Translating HbA1C into estimated
average glucose (eAG)
HbA1c
(%)
Estimated average glucose
(mmol/L)
6
7.0
7
8.6
8
10.2
9
11.8
10
13.4
11
14.9
12
16.5
Nathan DM et al for the A1c-Derived Average Glucose (ADAG) Study Group.
Translating the A1C assay into estimated average glucose values. Diabetes
Care 2008; 31: 1473– 1478
Glycaemic control:
Pharmacological therapy
General Considerations
• Type 2 diabetes is not a homogeneous disease
– Try to understand the pathophysiology in each individual
patient
• Majority of patients treated at PHC level
– Poor access to / use of laboratory testing esp. HbA1C and
renal function
– Increase number of agents that can be prescribed safely
by PHC doctors and nurses without complex monitoring
• Accumulating data on dangers of hypoglycaemia
as a risk marker for CV death
• Potential remission / cure in obese patients with
substantial weight loss
Glycaemic control: SEMDSA 2012 algorithm for type 2
diabetes
Use this algorithm only if the patient does NOT have features of severe decompensationa.
Progress down this algorithm within 3 months if HbA1C remains above 7% (or individualised target).
Choose therapies that are likely to produce the HbA1c reduction required to achieve the targetb
Do not proceed with drug therapy without annual serum eGFR measurement
Lifestyle measures plus
STEP 1: INITIATE AT LEAST
ONE ORAL DRUG AT
DIAGNOSIS
STEP 2: COMBINE ANY 2
DRUGSd
Preferred therapies
Metformin
Metformin
SU
STEP 3: COMBINE 3 DRUGS
Metformin + SU + Basal Insulin
(or Metformin + Pre-mix)
STEP 4: MORE ADVANCED
THERAPIES
Refer to specialist for
Basal + mealtime insulin
± Metformin ± Acarbose ±
Incretin
Alternative therapies for special circumstancesc
SU
DPP-4i
Acarbose
Incretin
Acarbose
Basal Insulin
Metformin + SU +
Incretin
Metformin + SU +
Acarbose
Metformin + Pre-mix insulin (if not used yet)
SU = sulphonylurea. Not glibenclamide ; DPP-4i = Dipeptidyl peptidase inhibitor; eGFR = estimated glomerular filtration rate
aSevere decompensation includes any of: FPG > 15mmol/L, HbA1C > 11%, marked polyuria & polydipsia, weight loss > 5% or ketoacidosis. Refer the
patient for specialist care (Step 4).
bRefer to Table I for expected HbA1C reductions.
cRefer to text
dIf at diagnosis, the patient’s HbA1C is >9% without features of severe decompensation, consider initiating therapy at STEP 2.
Glycaemic control: SEMDSA 2012 algorithm for type 2 diabetes
Use this algorithm only if the patient does NOT have features of severe
decompensationa.
Progress down this algorithm within 3 months if HbA1C remains above
7% (or individualised target).
Choose therapies that are likely to produce the HbA1c reduction
required to achieve the targetb
Do not proceed with drug therapy without annual serum creatinine /
eGFR measurement
aSevere
decompensation includes any of: FPG > 15mmol/L, HbA1C > 11%,
marked polyuria & polydipsia, weight loss > 5% or ketoacidosis. Refer the patient
for specialist care (Step 4).
bRefer
to Table for expected HbA1C reductions.
Glycaemic control: SEMDSA 2012 algorithm
Lifestyle
measures plus
STEP 1: INITIATE AT
LEAST ONE ORAL
DRUG AT
DIAGNOSIS
Preferred
therapies
Metformin
Alternative therapies for
special circumstances
SU
DPP-4i
Acarbose
Glycaemic control: SEMDSA 2012 algorithm
Lifestyle
measures plus
STEP 1: INITIATE AT
LEAST ONE ORAL
DRUG AT
DIAGNOSIS
STEP 2: COMBINE
ANY 2 DRUGSd
dIf
Preferred
therapies
Metformin
Metformin
SU
Alternative therapies for
special circumstances
SU
DPP-4i
Acarbose
Incretin
Acarbose
Basal
Insulin
at diagnosis, the patient’s HbA1C is >9% (but without features of
severe decompensation), consider initiating therapy at STEP 2
Glycaemic control: SEMDSA 2012 algorithm
Lifestyle
measures plus
STEP 1: INITIATE AT
LEAST ONE ORAL
DRUG AT
DIAGNOSIS
Preferred
therapies
Metformin
STEP 2: COMBINE
ANY 2 DRUGSd
Metformin
STEP 3: COMBINE 3
DRUGS
Metformin + SU +
Basal Insulin (or
Metformin + Pre-mix)
SU
Alternative therapies for
special circumstances
SU
DPP-4i
Acarbose
Incretin
Acarbose
Basal
Insulin
Metformin + SU
+ Incretin
Metformin + SU +
Acarbose
Glycaemic control: SEMDSA 2012 algorithm
Lifestyle
measures plus
STEP 1: INITIATE AT
LEAST ONE ORAL
DRUG AT
DIAGNOSIS
Preferred
therapies
Metformin
STEP 2: COMBINE
ANY 2 DRUGSd
Metformin
STEP 3: COMBINE 3
DRUGS
Metformin + SU +
Basal Insulin (or
Metformin + Pre-mix)
STEP 4: MORE
ADVANCED
THERAPIES
Refer to specialist for
Basal + mealtime
insulin
± Metformin ±
Acarbose ± Incretin
SU
Alternative therapies for
special circumstances
SU
DPP-4i
Acarbose
Incretin
Acarbose
Basal
Insulin
Metformin + SU
+ Incretin
Metformin + SU +
Acarbose
Metformin + Pre-mix insulin (if not
used yet)
Non-insulin therapies
Metformin
A1c ↓
↓↓
Therapeutic considerations
Disadvantages
Negligible hypoglycaemia risk
as monotherapy
Frequent GI side effects; 5-10%
discontinuation.
Weight neutral (promotes less
weight gain when combined
with other agents).
Lactic acidosis (rare).
Proven reduction in CV events
and mortality in obese subjects
(primary endpoint in UKPDS).
Renal impairment: reduce dose
to 1000mg/d if eGFR <45 and
discontinue if eGFR <
30ml/min/1.73m2
Metformin-XR has better GI
tolerability (is preferred to
switching to another class).
Vitamin B12 deficiency.
Contraindications: Cardiac
failure, PAD, Liver disease,
COPD, IV Contrast media
Metformin in the 2012 SEMDSA algorithm
• Step 1: Monotherapy
– Initial therapy of choice
– Start at time of diagnosis in all patients (overweight and
normal weight) unless specifically contra-indicated.
• Step 2: Dual therapy
– Can be added as a second-line agent in patients where
treatment has been initiated with any other class of antidiabetic drug.
• It is recommended that metformin therapy continue
even when other classes of anti-diabetic agents
(including insulin) are added subsequently.
Sulphonylureas
HbA1c
Therapeutic considerations
Generally well tolerated.
Proven reduction in
microvascular endpoints.
Relatively rapid glucoselowering response.
↓↓
Consider using another class in
patients at high risk of
hypoglycaemia.
If SU must be used in such
individuals, gliclazide-MR <
glimepiride / glipizide <
glibenclamide.
Disadvantages
Can cause severe hypo,
(especially glib. in renal
impairment).
Weight gain; 2 to 5kg; worst with
glibenclamide
May blunt myocardial ischemic
preconditioning (especially
glibenclamide).
Glibenclamide contraindicated if
eGFR<60ml/min/1.73m2;
glimepiride and glipizide dose
may need to be reduced.
SU in the 2012 SEMDSA algorithm
• Step 1: Monotherapy
– at diagnosis in persons intolerant of metformin, or in
normal weight individuals or those with marked
symptoms of hyperglycaemia.
• Step 2: Dual therapy
– Add as 2nd drug to metformin, or any other drug used
at Step 1
• Step 3: Triple therapy
– with metformin and basal insulin, or metformin and
incretin.
• In gestational diabetes, glibenclamide is the
sulphonylurea of choice (for specialist use only)
Non-insulin therapies
Meglitinides
HbA1c
Therapeutic considerations
Nateglinide is the least
↓ to ↓↓ effective secretagogue.
Disadvantages
Causes hypoglycemia.
Causes weight gain.
Targets postprandial glycemia;
use if fasting glucose is at
May blunt myocardial ischemic
target but HbA1c remains
preconditioning.
high.
Frequent dosing (mealtime).
Associated with less
hypoglycemia compared to
SU in the context of missed
meals; useful for patients with
unpredictable meals.
Meglitinides in the 2012 SEMDSA
algorithm
• Instead of SU
– If FPG is at target but HbA1C and PPG levels are
elevated
Non-insulin therapies
Acarbose
HbA1c
↓
↓
Therapeutic considerations
Disadvantages
Negligible hypoglycaemia risk
as monotherapy.
GI effects (gas, flatulence,
diarrhea).
Non-systemic effect.
Frequent dosing (mealtime).
Weight neutral.
Targets post-prandial
hyperglycaemia
49% reduction in CV risk (preplanned 2o analysis in STOPNIDDM Trial)
Non-insulin therapies
DPP-4 Inhibitors
HbA1c
↓
Therapeutic considerations
Disadvantages
Negligible hypoglycaemia risk
as monotherapy
Occasional reports of
urticaria/angioedema
Weight neutral.
Cases of pancreatitis observed
Improves post-prandial
control.
Newer agent with unknown
long-term safety.
Drug-specific
recommendations for hepatic
and renal disease.
DPP-4 inhibitors in the 2012 SEMDSA
algorithm
Contraindications to DPP-4 inhibitors
 There is a compelling indication for insulin therapy
 History of a serious hypersensitivity reaction to DPP-4 inhibitors.
 Patients with a history of acute pancreatitis, chronic or recurring
pancreatitis and those with pancreatic cancer.
DPP-4i and Acarbose in the 2012
SEMDSA algorithm
At Step 3: Add-on therapy as part of an oral 3-drug regimen
 Inadequate glycemic control on combination therapy with metformin
and sulphonylurea, and
 Patient is a poor candidate for insulin therapy, and
 Required reduction in HbA1C is < 1%
Discontinue after 3-6 months if HbA1C reduction is < 0.5%
DPP-4i and Acarbose in the 2012
SEMDSA algorithm
At Step 2: Add-on therapy as part of an oral 2 drug regimen
 Inadequate glycemic control on monotherapy with metformin or
sulphonylurea, and
 Unable to tolerate or has contraindications to addition of the 2nd as
yet unused agent from the above mentioned (metformin or
sulphonylurea), and
 Required reduction in HbA1C is < 1%
Discontinue after 3-6 months if HbA1C reduction is < 0.5%
DPP-4i and Acarbose in the 2012
SEMDSA algorithm
At Step 1: Use as monotherapy
 Candidate for oral therapy and is intolerant of or has
contraindications to use of both metformin and sulphonylureas, and
 Required reduction in HbA1C is < 1%
Discontinue after 3-6 months if HbA1C reduction is < 0.5%
GLP-1 Agonists
HbA1c
Therapeutic considerations
Negligible hypoglycaemia risk
as monotherapy.
↓↓
Disadvantages
Injectable
Initial GI side effects (nausea,
vomiting, diarrhea)
Enhances satiety and causes
weight loss.
Possible potential for improved Cases of acute pancreatitis
beta cell mass and function.
observed
Avoid initiating therapy in
individuals whom the potential
for dehydration poses a
considerable risk (e.g., frail
elderly, multiple co-morbid
conditions, etc.)
Causes C-cell hyperplasia /
medullary thyroid tumors in
animals (liraglutide)
Newer agent with unknown
long-term safety.
GLP-1 agonists in the 2012 SEMDSA
algorithm
Contraindications to GLP-1 use
 There is a compelling indication for insulin therapy
 History of hypersensitivity to GLP-1 agonist
 Renal failure (consult product label to assess suitability)
 Personal or family history of medullary thyroid carcinoma or Multiple
Endocrine Neoplasia syndrome type 2 (liraglutide).
 Patient has severe gastrointestinal disease, including gastroparesis.
 Patient has a history of pancreatitis
Relative exclusions to use include triglyceride level > 10mmol/L,
gallstones with intact gallbladder, and alcohol abuse.
 Planned treatment regimen includes a DPP-4 inhbitor, meglitinide or
acarbose (unstudied)
GLP-1 agonists in the 2012 SEMDSA
algorithm
At Step 3: Add on therapy as part of a 3 drug regimen:
Inadequate glycemic control on combination therapy with maximally
tolerated doses of metformin and sulphonylurea, and
 Patient is not a candidate for a 3rd oral agent from step 3, and
 Patient is a poor candidate for insulin therapy, and
 Required reduction in HbA1C is < 1.5% in order to reach patient
specific goal
Only continue therapy beyond 6 months if there has been a good
clinical response to therapy:
•HbA1C reduction >0.5% AND weight loss >3%, OR
•HbA1C reduction >1%, OR
•Weight loss >5%
GLP-1 agonists in the 2012 SEMDSA
algorithm
At Step 2: Add on therapy as part of a 2 drug regimen:
 Patient has not achieved desired HbA1c and with optimum doses of
one oral agent and is not a candidate for any other agent (oral or
insulin) available at Step 2; and
 Required reduction in HbA1C is < 1.5% in order to reach patient
specific goal
Only continue therapy beyond 6 months if there has been a good
clinical response to therapy:
•HbA1C reduction >0.5% AND weight loss >3%, OR
•HbA1C reduction >1%, OR
•Weight loss >5%
Circumstances where insulin therapy
may not be desirable
Insulin allergy
Failure or inability to master injections or self-titration
Frequent or severe hypoglycemia despite multiple dosage
adjustments
Circumstances exist where the risk of severe hypoglycemia and/or its
potential consequences are significant and/or catastrophic
• Workers with frequent rotating shifts
• Occupations such as truck or bus drivers / heavy machine operators)
Obesity related morbidity which has worsened or is likely to worsen
significantly with weight gain from insulin therapy
Thiazolidenediones
• Rosiglitazone
– Increased CV outcome events
– Voluntarily withdrawn in SA
• Other problems
– Fluid retention, ppt heart failure
– Weight gain
– Long bone fractures
– Bladder cancer
• Not included in the algorithm
Lipids
Lipid targets
• Aligned with LASSA and SA Heart
Total cholesterol
< 4.5mmol/L
LDL cholesterol
< 1.8mmol/La
HDL cholesterol
> 1.0 mmol/L (men)
> 1.2 mmol/L (women)
Triglycerides
< 1.7mmol/L
The LDL-cholesterol goal is < 2.5 mmol/l in patients with type 2
diabetes who meet all of the following criteria:
a
1. No cardiovascular disease and no chronic kidney disease
2. Less than 40 years old OR duration of diabetes less than 10 years
3. No other cardiovascular risk factor
Lipids
• Measure 10-hr fasting lipid profile at
diagnosis
• Subsequent monitoring targeted only at
abnormalities (no need for full profile in
every patient)
• Specialist referral: TG > 5 mmol/l in the
controlled diabetic, or > 15 mmol/l before
treatment.
Initiate statin therapy in all patients with:
• Existing cardiovascular disease (i.e.
ischaemic heart disease, cerebrovascular
disease or peripheral vascular disease).
• Chronic kidney disease (eGFR < 60
ml/minute/1.73m2).
• Age >40 years or diabetes duration >10 yrs
with one or more additional cardiovascular
risk factor
– hypertension, cigarette smoker, low HDL-cholesterol level, family
history of early coronary heart disease, microalbuminuria
Statins
• Consider statin + ezetimibe if patient is
unable to tolerate / achieve LDL cholesterol
goals on the maximum dose of a highly
potent statin
• Simvastatin should not be co-prescribed
with most antiretroviral agents
• Use low doses of simvastatin with CCB’s.
• Never initiate therapy with Simvastatin 80
mg/day
Referrals
• Baseline TG >15mmol/L
• TG > 5mmol/l with low HDL, despite good
glycaemic control
• Combination therapy (statin + fibrate) being
considered.
Blood pressure
Highlights: Blood pressure targets
• Previous SBP target lacks clinical evidence
base
• Definition of hypertension
– SBP ≥ 140mmHg
– DBP ≥ 80mmHg
• Target BP
– SBP 120-140mmHg
– DBP 70-80mmHg
Rhonda M, Cooper-DeHoff, Egelund EF, Pepine C. Blood pressure lowering in patients with
diabetes—one level might not fit all. Nature Reviews Cardiology. 2011;8:42-49
In-hospital management: regular meal
pattern maintained
• Well controlled
– Continue usual therapy
• Poorly controlled: Basal bolus therapy
– Estimate TDD (conservatively 0.2 to 0.5u/kg)
– Basal (50%) + prandial (50%) insulin
• Correction dose insulin
– Correction factor (CF) = 100/TDD or 85/TDD
– Correction dose = (Measured BG – target BG) ÷
CF
Umpierrez G, Smiley D, Zisman A, et al. Randomized study of basal-bolus insulin therapy in the inpatient
management of patients with type 2 diabetes (RABBIT 2 trial). Diabetes Care. 2007;30:2181-2186.
Example
• 45yr old weighing 100kg taking Actraphane 40u/20u BID prior
to hospitalisation
– Estimated TDD = 60u
– Give 30u NPH/long acting analogue at night +
– 10u TDS rapid analogue or short acting regular
– Target preprandial glucose 7.8mmol/L; <10 at any other time
– CF = 100/60 = 1.7 (85/60 for regular human insulin)
• If post-meal BG is 20mmol/L, correction dose = 20 (current) - 10
(target) x 1.7 =17u
• Add 80% of daily correction dose to next days basal-bolus
insulin
In-hospital management: regular meal
pattern disrupted
• NPO
– Use only correction dose insulin, or NPH twice daily or long acting
analogue once daily
• Bolus eneteral feeds
– Basal bolus therapy + correction doses
• Continuous enteral feeds
– NPH 12-hrly or long acting analogue ± scheduled regular insulin,
OR
– Premixed insulin 8-hourly
• TPN
– IV insulin infusion (infusion protocol), or
– 50% TDD added to TPN as regular insulin, and 50% given as basal
– Calculate TDD : 1u/10g carbohydrate
In-hospital management: critically ill
patients
• Insulin infusion preferred if facilities and staff training exist; if not
use basal-bolus + correction doses
• Target BG is 7.8 – 10.0 mmol/L; not lower than 6.1mmol/L
• Mix 50u insulin in 100ml 5% dextrose water
• Detailed response protocol needed for staff
Glucose
(mmol/l)
10.0-13.9
14.0-16.6
16.7-20.0
>20.0
Bolus
injection
4 units
6 units
8 units
10 units
Infusion rate
2 u/hr
3 u/hr
4 u/hr
5 u/hr
Adapted from Gunderson Lutheran Medical Center protocol Am J Health –Syst Pharm 2007; 64: 392
ADA/EASD 2012 Algorithm

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