MODERN ART in TYPE 2 DIABETES Ken McHardy CRAIGMONIE HOTEL, INVERNESS 11 TH Nov 2011

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 Adapted from Bailey CJ et al. Int J Clin Pract 2004; 58: 867–876. Insulin resistance Insulin production Glucose level Beta-cell dysfunction TIME

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 1 st Line a.LIFESTYLE b.METFORMIN (or SU if BM<25) 2 nd 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

2 nd 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 TZD if no CCF DPP-IV Inhibitor if wt gain a concern ORAL (continue MF/SU if tolerated) INJECTABLE (continue MF/SU if tolerated) Bedtime INSULINGLP-1 agonist SIGN 116 ALGORITHM

3 rd LINE OPTIONS ORAL aGLITAZONES bGLIPTINS INJECTABLE cGLP-1 ANALOGUES dINSULIN ? Long-term safety; ? Cost effective

PIOGLITAZONE 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 3 rd 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 3 rd Line Options (b)

GLIPTINS SAXAGLIPTIN on GJF summer 2011 Standard 5mg dose rejected by GJF % cheaper dose but ?efficacy 2.5mg dose licensed in moderate CKD Only as add-on to Metformin So new approved option eGFR (?Linagliptin coming early 2012) 3 rd 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) 3 rd 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 ) Drug cost/day: p (Once weekly soon!) 3 rd 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) : p eGFR>60 only 3 rd 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) 3 rd Line Options (d)

COMPARATIVE INSULIN COSTS Drug cost per 10 units per day using 3ml pen cartridges as in BNF 62 [Sep 2011]  Humulin I12.7p  Insulatard15.3p ( +20%)  Lantus27.7p (+118%)  Levemir28.0p (+120%)  [Insuman Basal11.7p (-8%) ] 3 rd Line Options (d)

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 HbA 1C falls > 0.5% (5.5 mmol/mol) in 3-6 months. [SIGN 116] Only continue 3 rd line therapy if beneficial metabolic response : glitazone/gliptin at least 0.5% fall in HbA 1C in 6/12; GLP-1 Analogue at least 1% fall in HbA 1C and 3% wt loss in 6/12). [NICE 87] Potential Annual Savings e.g. Pio (30) = £468 Sita = £434 Exen = £828 Lira (1.2) = £952

SO WHAT’S NEXT?