Transcript new treatments for type 2 diabetes

CRAIGMONIE HOTEL, INVERNESS 11TH Nov 2011
MODERN ART in
TYPE 2 DIABETES
Ken McHardy
NEW TREATMENTS?
• DIETS, DEPRIVATION AND DRUDGERY
• PILLS, POTIONS AND PANACEAS
• ‘NEW’ GUIDELINES
NICE CG66 & CG87
SIGN 116
BNF 62
LOCAL FORMULARY
GRAMPIAN DIABETES GUIDELINES 2011
• EVALUATION & VALUE of DRUG USE
TYPE 2 DIABETES
• PREVALENT
• MORBIDITY & MORTALITY
• MODIFIABLE COURSE
• EVOLVING CONDITION
Evolution of Type 2 Diabetes
Insulin
resistance
Glucose
level
Beta-cell
dysfunction
Insulin
production
TIME
Adapted from Bailey CJ et al. Int J Clin Pract 2004; 58: 867–876.
NEW TREATMENTS FOR TYPE 2
• REMEMBER LIFESTYLE ISSUES!
• ‘NEWER DRUGS’
– Metformin mr - Glitazones
– Gliptins
- GLP 1 Analogues
• NEWER GUIDELINES
– When to start
– When to stop
– Isophane insulin born again!
SIGN 116 ALGORITHM
1st Line
a. LIFESTYLE
b. METFORMIN (or SU if BM<25)
2nd Line
a. LIFESTYLE plus
b. METFORMIN and SU
METFORMIN mr
• GI side effects common with Metformin
• Build up gradually
• Small dose better than none
• Metformin mr may reduce GI effects
• Metformin mr may increase tolerated dose
• 2g/d: regular 7.3p; mr 38.1p
• Use it appropriately, not routinely
SIGN 116 ALGORITHM
2nd LINE OPTIONS
Normally LIFESTYLE and METFORMIN and SULPHONYLUREA
review and if
not reaching
target move
to 3rd line
3rd LINE OPTIONS In addition to lifestyle measures, adherence to medication
and dose optimisation, ADD OR SUBSTITUTE WITH ONE OF
ORAL (continue MF/SU if tolerated)
INJECTABLE (continue MF/SU if tolerated)
TZD
•if no CCF
Bedtime INSULIN
DPP-IV Inhibitor
•if wt gain a concern
GLP-1 agonist
3rd LINE OPTIONS
ORAL
a GLITAZONES
b GLIPTINS
INJECTABLE
c GLP-1 ANALOGUES
d INSULIN
• ? Long-term safety; ? Cost effective
PIOGLITAZONE
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•
•
•
•
•
•
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Lowers Insulin Resistance
Fluid retention/ cardiac failure
Weight gain?
Care with raised transaminase (ALT)
No increased IHD risk
Long bone fractures
Bladder cancer risk?
15 mg/d : 92.3p; 30 mg/d : 128.2p
3rd Line Options (a)
GLIPTINS
• Prevent breakdown of GLP 1 (DPP4i)
• GLP 1 raises insulin, lowers glucagon
and slows gastric emptying
• SITAGLIPTIN 100mg od: 118.8p
• Nausea; weight neutral
• Can enhance hypoglycaemic effect of SU
• Avoid if eGFR<50……. but
3rd Line Options (b)
GLIPTINS
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SAXAGLIPTIN on GJF summer 2011
Standard 5mg dose rejected by GJF 2010
5% cheaper dose but ?efficacy
2.5mg dose licensed in moderate CKD
Only as add-on to Metformin
So new approved option eGFR 30-50
(?Linagliptin coming early 2012)
3rd Line Options (b)
GLP-1 ANALOGUES
• ‘Synthetic GLP-1’; resists breakdown
• GLP 1 raises insulin, lowers glucagon
and slows gastric emptying
• Subcutaneous injection
• Nausea; ?weight loss
• Can enhance hypoglycaemic effect of SU
• BMI >35 (NICE); >30 (SIGN) (lower BMI if
e.g. occupational issues, non-Caucasian)
3rd Line Options (c)
GLP-1 ANALOGUES
EXENATIDE (Byetta; Lilly)
• 5 mcg x2 daily; 10 mcg x2 daily after 4 wk
• 1 hour before meals
• eGFR>30 (lower dose 30 - 50)
• Drug cost/day: 227.5 p
• (Once weekly soon!)
3rd Line Options (c)
GLP-1 ANALOGUES
LIRAGLUTIDE (Victoza; NovoNordisk)
• 0.6 mg x1 daily unrelated to meals
• 1.2 mg x1 daily after 1-4 weeks
• 1.8 mg x1 not approved in Grampian
• Drug cost/day (1.2 mg) : 261.6 p
• eGFR>60 only
3rd Line Options (c)
SUPPLEMENTARY INSULIN
• Continue Metf + SU; (stop other OHAs)
• Use NPH insulin once daily BBed
• Save analogues for definite problems
• Hypos marginally fewer; cost greater
• HTA paper:
– over £300k per QALY (Lantus)
– over £400k per QALY (Levemir)
3rd Line Options (d)
COMPARATIVE INSULIN COSTS
Drug cost per 10 units per day using 3ml pen
cartridges as in BNF 62 [Sep 2011]
 Humulin I
12.7p
 Insulatard
15.3p
( +20%)
 Lantus
27.7p
(+118%)
 Levemir
28.0p
(+120%)
 [Insuman Basal 11.7p
3rd Line Options (d)
(-8%)
]
KNOWING WHAT TO START
•
•
•
•
Know and use the guidelines but…
Remember they are only guidelines
Real life is more complex
Needs experience and professionalism
and a patient-centred approach
• Put people before numbers
• Don’t overdo glycaemic ‘control’
• Know when to stop……
KNOWING WHEN TO STOP
• at each stage, continue medication if EITHER
individualised target achieved OR HbA1C falls > 0.5%
(5.5 mmol/mol) in 3-6 months. [SIGN 116]
• Only continue 3rd line therapy if beneficial metabolic
response : glitazone/gliptin at least 0.5% fall in HbA1C
in 6/12; GLP-1 Analogue at least 1% fall in HbA1C and
3% wt loss in 6/12). [NICE 87]
• Potential Annual Savings
e.g. Pio
= £468
Exen = £828
(30)
Sita
= £434
Lira (1.2) = £952
SO WHAT’S NEXT?