Transcript to the slides from this event

NICE 2015
guidelines to help us treat T2 diabetes in 2016?
Paul Newrick
Consultant Physician WAHNHST
2016
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Achieving normal blood glucose levels
– still remains key to reducing diabetic complications
Diabetes Control and
Complications Trial
Relative Risk (%)
15
Retinopathy
Nephropathy
Neuropathy
Microalbuminuria
13
11
5
p<0.0001
UKPDS
9
7
5
3
1
6
7
8
9
10
HbA1c (%)
11
12
1
21% decrease per 1% decrement in HbA1c
0.5
05
2
6
7
8
9
10
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Choosing the HbA1c target
Cardiovascular safety is the issue
Mortality
6.4%
HR 1.52
3
7.5%
Hazard ratio = 1
HbA1c
10.5%
HR 1.79
What are the challenges for diabetes care in 2016?
• Numbers!
• Toxic environment…obesity
• Converting knowledge into behaviour
• Multiple therapeutic choices/decisions
• Integrated care
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NICE CG87 2009
the management of type 2 diabetes
• Issued May 2009
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National Institute for Health and Clinical Excellence. Type 2 diabetes: The management of type 2 diabetes. London: NICE, 2009.
ADA/EASD position statement 2015:
when the goal is to avoid weight gain
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Effect of glucose lowering agents on HbA1c when added to
metformin
• All classes of second-line agents added to metformin significantly reduced HbA 1c from
baseline relative to metformin alone; there were no statistically significant differences
between drug classes
Results of a MTC based on 40 RCTs (n=17,795)
Treatment
MTC estimate (95% CI)
SUs
–0.79 (–0.95, –0.63)
Meglitinides
–0.64 (–0.93, –0.37)
TZDs
–0.82 (–1.00, –0.66)
DPP-4 inhibitors
–0.80 (–0.95, –0.65)
α-glucose inhibitors
–0.74 (–0.98, –0.50)
GLP-1 receptor agonists
–0.82 (–1.05, –0.59)
Basal insulin
–0.82 (–1.16, –0.47)
Biphasic insulin
–0.97 (–1.33, –0.61)
-2.0
Favours
treatment
-1.5
-1.0
-0.5
Favours
placebo
-0
-0.5
Difference in change from baseline in HbA1c, % (95% CI)
DPP-4=dipeptidyl peptidase-4; GLP-1=glucagon like peptide-1; MTC=mixed treatment comparison; RCT=randomised controlled trial; SU=sulphonylurea;
TZD=thiazolidinedione.
Results7of a MTC of the effect of adding second-line antidiabetes treatment versus placebo in adults with type 2 diabetes taking metformin on change from
baseline in HbA1c. The authors conducted meta-regression and sensitivity analyses to test the robustness of the reference case analysis. Overall, meta-regression
and sensitivity analyses yielded minimal differences from the reference case.
Adapted from: McIntosh B et al (2011) Open Med 5:e35–48
T2DM in 2009
– choices, choices, choices…
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Effect of glucose lowering therapies on body weight
UKPDS: up to 8 kg in 12 years1
Change in weight from baseline (kg)
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Baseline weight: 85 kg
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Insulin (n=409)
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5
4
SU (glibenclamide) (n=277)
3
2
Conventional (n=411)
1
Metformin (n=342)
0
0
-1
3
6
Years
9
12
• Change in bodyweight was similar in the metformin and conventional control groups, and less than the
increase in bodyweight observed in patients assigned intensive control with sulphonylureas or insulin
n=at baseline.
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Conventional
treatment; diet initially, then SUs, insulin and/or metformin if fasting plasma glucose (FPG) >15 mmol/L (>270 mg/dL).
SU=sulphonylurea; UKPDS=UK Prospective Diabetes Study.
Adapted from UKPDS Group (1998) Lancet 352: 854–65
Sitagliptin vs SU Add-on Therapy to Metformin
LS mean change in body weight over time
Hypoglycaemia
50
Sitagliptinb 100 mg o.d + metformin* (n=389)
3
Glipizide 5-20 mg/day + metformin* (n=416)
40
Incidence (%)
Body weight (kg ± SE)
2
1
0
32%
30
P<0.001
20
-1
10
-2
-3
5%
0
0
12
24
Weeks
38
52
Week 52
Sitagliptinb 100 mg o.d + metformin* (n=584)
Glipizide 5-20 mg/day + metformin* (n=588)
NICE final updated guidance Dec 2015
Type 2 diabetes in adults – updated areas
• Patient-centred care
• Lifestyle and diet
• Education – structured, group preferred, annually
• Aspirin/Clopidogrel – not for 1ary prevention
• BP – aim for <140/80 unless high risk aim for <130/80
• SMBG – assess annually if being used
• Glycaemic management - drugs
• Glycaemic management - insulin
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NICE final updated guidance Dec 2015
Type 2 diabetes in adults
• Patient-centred care
‘Adopt an individualised approach to diabetes care that is tailored to the
needs and circumstances of adults with T2 diabetes…’
Consider older patient’s broader health and social care needs and potential to
benefit
All patients should have opportunity to make informed choices about treatment,
and treatment should take into account their needs and preferences
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NICE final updated guidance Dec 2015
Type 2 diabetes in adults
• Glycaemic management
Measure HbA1c 6-monthly (3-monthly if unstable/regimen changes)
Target HbA1c 48 (53-58 at Step 2; higher if needed for optimum risk: benefit ratio)
No routine offer of SMBG
• Drug treatment – complex network and health-economic analysis with many
unresolved issues and incomplete evidence base
Start - Metformin (stop if eGFR<30) – try MR if not tolerated – otherwise DPP-4,
Pioglitazone or SU
1st intensification (HbA1c≥58 target 53) – Add DPP-4 – otherwise Pioglitazone or SU
or SGLT
2nd intensification (HbA1c≥58 target 53) – Add a 3rd oral agent or GLP-1 agonist or
insulin (depending on psychological and/or BMI issues)
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Treatment should take into account patient preferences
SGLT-2 may be appropriate add-on
No guidance on statins
NICE final updated guidance Dec 2015
Type 2 diabetes in adults
• Insulin
Start with NPH od (HbA1c<75) or pre-mix bd (HbA1c 75+)
Detemir or Glargine if would reduce frequency of injections to 1
if otherwise needing NPH bd + OHAs
if recurrent hypoglycaemia
if would reduce need for outside assistance
if not at target
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NICE and cardiovascular safety
• A vital constituent of holistic diabetes care
• In the long term at least no harm should accrue
• Data on CVS safety not included but we have some reassurance from trials:
Sitagliptin – TECOS
Alogliptin - EXAMINE
Saxagliptin – SAVOR-TIMI (heart failure signal)
Empagliflozin – EMPA-REG (CVS mortality RR 0.62)
Lixisenatide - ELIXA
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TECOS
• Integration with usual diabetes care
1ary Objective
To demonstrate that the risk of cardiovascular events in patients treated with
sitagliptin in addition to usual care was non-inferior to that in patients treated
without sitagliptin in addition to usual care
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Green JB et al. NEJM 2015; DOI: 10.1056/NEJMoa1501352
Summary of Results
• For the primary composite cardiovascular outcome
(CV death, nonfatal MI, nonfatal stroke, or hospitalization for unstable
angina) sitagliptin, compared with placebo, was noninferior, and not
superior
• For the secondary composite cardiovascular outcome
(CV death, nonfatal MI, or nonfatal stroke) sitagliptin, compared with
placebo, was noninferior, and not superior
• The rate of hospitalization for heart failure did not differ between
sitagliptin and placebo treatment groups
• The incidence of severe hypoglycemia did not differ
between sitagliptin and placebo treatment groups
• The utility of sitagliptin as a glucose-lowering agent was confirmed by
the more frequent initiation of insulin therapy and the greater need for
additional antihyperglycemic agents in the placebo group compared with
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the
sitagliptin group
Green JB et al. NEJM 2015; DOI: 10.1056/NEJMoa1501352
Your average patient…
• Average age
• Average weight
• Average lifestyle
• Average cardiovascular risk profile
What is your 1st choice drug?
What is your 2nd choice drug?
and why?!
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T2DM in 2016 – choices, choices…
but possibly clearer?
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Comments?
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