1. No category

GLP1 treatment options
May 2014
Incretin Effect
Incretin Hormones
Incretin hormones are produced by the
gastrointestinal tract in response to nutrient
entry and are necessary for the maintenance of
glucose homeostasis.
• GLP 1 (glucagon like pepetide 1)
• GIP ( glucose dependent insulinotrophic
polypeptide)
Beyond Glycemic Control: The Effects of Incretin Hormones in Type 2 Diabetes -- Martin 34 (3): 66S -- The Diabetes Educator
Therapeutic potential of GLP-1 and
GIP
• The incretin effect is diminished in patients
with type 2 diabetes1,2
–GIP secretion is normal, but its action is
diminished
–GLP-1 secretion is diminished, but its
action is preserved
1Nauck
MA, et al. J Clin Invest 1993;91:301–307; 2Nauck M, et al. Diabetologia 1986;29:46–52; 3Nauck MA, et al. Diabetologia
1993;36:741–744; 4Larsson H, et al. Acta Physiol Scand 1997;160:413–422; 5Drucker DJ. Diabetes Care 2003;26:2929–2940.
GLP-1 Effects in Humans: Understanding
the Glucoregulatory Role of Incretins
GLP-1 secreted upon
the ingestion of food
Promotes satiety and
reduces appetite
a-cells:
↓ Postprandial
glucagon secretion
b-cells:
Enhances glucose-dependent
insulin secretion
Liver:
↓ Glucagon reduces
hepatic glucose output
Other effects
Stomach:
Helps regulate
gastric emptying
Cardiac Tissue
Pulmonary
? Skeletal muscle
? Adipose Tissue
GLP-1: Glucagon-like peptide 1
Adapted from Flint A, et al. J Clin Invest. 1998;101:515-520; Adapted from Larsson H, et al. Acta Physiol Scand. 1997;160:413-422;
Adapted from Nauck MA, et al. Diabetologia. 1996;39:1546-1553; Adapted from Drucker DJ. Diabetes. 1998;47:159-169.
EXENATIDE
bd
EXENATIDE
one/week
LIRAGLUTIDE
LIXISENATIDE
Monthly cost
£68.24
£73.36
£78.48
£54.14
Frequency
Twice daily up
to 1 hours pre
food- 6 hours
apart
Once weekly
Once daily
Once daily up
to one hour
before a meal
Timing
Pre-breakfast
and preevening meal
Same day each
week
Same time
each day
Prior to first or
largest CHO
load meal of the
day
Restrictions
eGFR <30
eGFR<50
eGFR <60
eGFR< 30
Dose
5 micrograms
BD increase to
10 micrograms
BD after 28
days
2mg once
weekly- takes 7
weeks to reach
steady state
0.6mg for 2
weeks
increasing to
1.2mg max
dose
10 micrograms
increasing to 20
micrograms
OD after 2
weeks
EXENATIDE
bd
EXENATIDE
one/week
LIRAGLUTIDE
LIXISENATIDE
Blood glucose
level most impact
on
Post meal
Post meal
Fasting
Post meal
Side effects
Transient
Nausea
Some transient
nausea
Pea sizes
pelletts may be
felt at the
injection site
last 6 weeks
Some transient
nausea lower
GI side effects
Some transient
nausea
Minimise side
effects
Give
immediately
before food
Comments
Impact on
satiety
increases with
time before
meal
Give
immediately
before food
Takes 7 weeks
for stable state
to be achieved
Impact on
satiety
increases with
time before
meal
Combinations options
EXENATIDE bd EXENATIDE
one/week
LIRAGLUTIDE
LIXISENATIDE
Metformin and/or
sulphonylurea
Yes
Yes
Yes
Yes
Metformin and/or
Pioglitazone
Yes
Yes
Yes
Yes
Metformin and/or
Pioglitazone with
Basal insulin
Yes
No
Levemir only
Yes
can be added to
Liraglutide
Metformin,
Sulphonylurea
and Basal insulin
NO
NO
NO
NO
Blood-glucose lowering therapy – CG 87 algorithm – in entirety
SGLT2
HbA1c ≥ 6.5%1 after trial of lifestyle
interventions
Sulphonylurea
Consider sulphonylurea 4 here if:
•not overweight (tailor the assessment of body-weightassociated risk according to ethnic group 3), or
•metformin is not tolerated or is contraindicated, or
•a rapid therapeutic response is required because of
hyperglycaemic symptoms
Metformin
HbA1c < 6.5%
Monitor for deterioration
HbA1c ≥ 48mmol/mol
HbA1c < 6.5%
Monitor for
deterioration
HbA1c ≥
48mmo/m
ol
Consider a sulphonylurea for
people with erratic lifestyles
Consider adding a DPP4 inhibitor or a
TZD if metformin is not tolerated or is
Consider substituting a DPP4
inhibitor or a TZD for an SU if
there is significant risk of hypos or
an SU is contraindicated or is not
tolerated
contraindicated
Metformin +
DPP4 inhibitor
or a TZD
Metformin +
sulphonylurea
HbA1c < 7.5%
Monitor for
deterioration
HbA1c ≥
59mmol/m
o
Add insulin
- particularly if subject is
markedly hyperglycaemic
Insulin + metformin + sulphonylurea
Consider adding DPP4
inhibitor or TZD if insulin is
unacceptable (employment,
social issues, obesity)
Consider adding exenatide to
metformin and SU if:
•BMI ≥ 35 in patients of
European descent, or
•BMI < 35 and insulin
unacceptable or weight-loss
would benefit other
co-morbidities
HbA1c ≥
59mmol/mol
Sulphonylurea + DPP4 inhibitor or a
TZD
HbA1c < 7.5%
Monitor for
deterioration
HbA1c ≥
59mmol/mol
Metformin + SU +
sitagliptin
or
Metformin + SU + TZD
or
Metformin + SU +
HbA < 7.5% exenatide
Monitor for
HbA1c ≥
deterioration
59mmol/mol
1c
HbA1c < 7.5%
Monitor for
deterioration
Start insulin
Increase insulin dose and intensify regimen over time
HbA1c ≥
59mmol/m
HbA1c < 7.5%
Monitor for
deterioration
Consider pioglitazone with insulin if:
•A TZD has previously had a marked glucose-lowering
effect, or
•Blood-glucose control is inadequate with high-dose
insulin
HbA1c ≥
59mmol/mol
HbA1c < 7.5%
Monitor for
deterioration
NICE CG87
Blood-glucose lowering therapy – Therapeutic choices
Consider
First
Consider
Second
Metformin
SU
SU
TZD
1. Add to Met
2. Add to SU
Insulin
resistance
Driver
DPP4 inhibitor
1. Add to Met
2. Add to SU
Hypoglycaemia
a concern
Driver
Elderly
Consider eGFR
SGLT2
1. Add to Met
2. Add to SU
Weight an issue
eGFR>60
Under 75
No Thrush
No UTI
No Diuretics
No postural hypotension
Blood-glucose lowering therapy – Therapeutic choices
Consider
First
Metformin
HbA1c ≤ 48mmol/mol
SU
Monitor for deterioration
Did treatment added result in drop in
HbA1c?
Consider
Second
SU
TZD
1. Add to Met
2. Add to SU
Consider
Third
DPP4 inhibitor
1. Add to Met
2. Add to SU
NPH Insulin
Other Insulin
TZD
DPP-4 inhibitor
As per CG66
1.Long-acting
analogue – as
an alternative
to starting
NPH
2.Premix insulin
as per CG66
1.Added to Met
+ SU
2.Added to Met
+ SU if poor
response to
DPP-4 inhib or
not tolerated.
1.Added to Met
+ SU
2.Added to Met
+ SU if poor
response to
TZD or not
tolerated.
SGLT2
1. Add to Met
2. Add to SU ?
SGLT2
Currently not
recommended
Canagloflozin
will be given
Triple
GLP 1
1.Added to Met
+ SU
2.Added to Met
+ Pio
Blood-glucose lowering therapy – Therapeutic choices
Consider
First
Metformin
HbA1c ≤ 48mmol/mol
SU
Monitor for deterioration
Did treatment added result in drop in
HbA1c?
Consider
Second
SU
TZD
1. Add to Met
2. Add to SU
Consider
Third
NPH Insulin
1.Added to Met
+ SU
2.Added to Met
+SGLT2
Consider
Fourth
DPP4 inhibitor
1. Add to Met
2. Add to SU
SGLT2
1. Add to Met
2. Add to SU
Other Insulin
TZD
DPP-4 inhibitor
Canagloflozin
1.Long-acting
analogue – as
an alternative
to starting
NPH
2.Premix insulin
1.Added to Met
+ SU
2.Added to Met
+ SU if poor
response to
DPP-4 inhib or
not tolerated.
1.Added to Met
+ SU
2.Added to Met
+ SU if poor
response to
TZD or not
tolerated.
1.Added to Met
+ SU
2.Added to Met
+ Pio
NPH Insulin
Other Insulin
1.Added to Met
+ SU
2.Added to Met
+ pio
3.Added to Met
+GLP1
Stop Gliptin
/SGLT2/ PIO
1.Long-acting
analogue – as
an alternative
to starting
NPH
2.Premix insulin
GLP 1
1.Added to
Met + SU
2.Added to
Met + Pio
Stop
Gliptin/SGLT2
GLP 1
1.Added to Met
+ SU
2.Added to Met
+ Pio
Group work
Case study - 1
Mr S
• Type 2 for 8yrs
• Last 3 HbA1c’s 60 mmol/mol,
66 and 73 mmol/mol
• Metformin MR 1500mg,
Pioglitazone 15mg, Glimepiride
4mg
• BMI 35
• Factory manager – works shifts
Case study - 1
Mr S
• Type 2 for 8yrs
• Last 3 HbA1c’s 60 mmol/mol, 66 and
73 mmol/mol
• Metformin MR 1500mg, Pioglitazone
15mg, Glimepiride 4mg
• BMI 35
• Factory manager – works shifts
GLP1 –an option
BMI >35
HbA1c <75mmol/mol
Case Study - 2
Mr M
• Devout Moslem – prays 5x/day and
fasts for Ramadan
• Eats 9am, 12md, 4pm and 9pm
• Metformin 850mg BD , Pioglitazone
30mg and Glimepiride 4mg OD
• Last 3 HbA1c’s 63, 69,74 mmol/mol
• BMI 30
• Speaks some English
Case Study - 2
Mr M
• Devout Moslem – prays 5x/day and fasts for
Ramadan
• Eats 9am, 12md, 4pm and 9pm
• Metformin 850mg BD , Pioglitazone 30mg and
Glimepiride 4mg OD
• Last 3 HbA1c’s 63, 69,74 mmol/mol
• BMI 30
• Speaks some English
GLP 1 an option
BMI 30 – meets NICE- ethnicity
adjusted
HbA1c <75mmol/mol
Case Study - 3
Mrs B
• Last 3 HbA1c’s 56, 65
and 77mmol/mol
• BMI 25
• Glimepiride 4mg OD,
Metformin 500mg TDS,
Pioglitazone 30mg OD
• Not happy about
HBGM
Case Study - 3
Mrs B
• Last 3 HbA1c’s 56, 65 and
77mmol/mol
• BMI 25
• Glimepiride 4mg OD, Metformin
500mg TDS, Pioglitazone 30mg
OD
• Not happy about HBGM
GLP1 not an option
BMI 25
HbA1c rising rapidly needs insulin
Case study 4
•Mr D
•42 year old sales rep
•Type 2 diabetes for 6 years
•Has managed to lose 3 stone
in weight since diagnosis.
• BMI 27
• Last 3 HbA1c’s 50, 75,
and 90 mmol/mol
•Metformin MR 1500mg OD,
Glimepiride 4mg OD,
Case study 4
•Mr D
•42 year old sales rep
•Type 2 diabetes for 6 years
• BMI 35
• Last 3 HbA1c’s 50, 75,
and 90 mmol/mol
•Metformin MR 1500mg OD,
Glimepiride 4mg OD,
GLP 1 not an option
HbA1c rising rapidly needs insulin
Injection Technique
On the diagrams provided draw
anatomically correct possible
injection sites
Anatomy of the Skin
23
Ideal Distribution of Insulin
Injection Sites
Lifting a Skin Fold
Options for injection rotation
Hypoglycaemia
4 is the floor
Mild Hypoglycaemia
•
•
•
•
•
•
•
•
Tingling hands,feet,lips or tongue
Sweating
Dizziness
Trembling Hunger
Blurred vision
Difficulty in concentration
Palpitations
Occasional headaches
Mild “hypo” – treatment
15-20g CHO
•
•
•
•
4-6 Dextrose tablets
Glucochek 1-2
100mls lucozade
4-5 jelly babies
• Eat next meal if due
OR
• Have a snack, e.g.
banana/bread
/biscuits etc
DVLA to be informed
• Insulin treated
• Class 2 on any oral medication or
injectable
Car Driver At risk of Hypoglycaemia
Insulin –Treated
• Within 2 hours of commencing driving and every 2 hours
whilst driving
• Do not drive if BGL less than 4mmols
• If BGL less than 5mmols treat with snack
• If hypoglycaemia develops while driving ,stop ,switch off
engine, remove keys from ignition & move from driver’s seat.
• Treat hypoglycaemia with glucose tablets/carbohydrate. Do
not resume driving for 45 mins after blood glucose back to
normal.
Sulphonylureas and Glindes
• It may be appropriate to test regularly at times relevant to
driving
Questions