1. Diabetes Learning Event 7th October 2016
New NICE Guidelines for Managing blood glucose in adults with type 2 diabetes
Mark Chamley
Clinical Lead
Lambeth Diabetes Intermediate Care Team

2. NICE T2DM Guideline December 2015
What’s new – drugs and targets
South East London Blood Glucose Control Management Pathway for Adults with Type 2 Diabetes Mellitus
Local recommendations in drug choices
Case studies

3. Cost of diabetes prescribing in UK
123,610 prescriptions for diabetes every day
£800 million/ year
£213 – £369/ patient with diabetes
Large regional variation reflecting local prescribing practice but no clear association between expenditure and outcomes
Source: HSCIC 2014

4. Effects of diabetes control on complications - UKPDS40 P= 35 30
P=0.0099
P=0.046 25
P=0.015
% risk reduction 20
P=0.052 15
P=0.029
The UKPDS was the largest study of diabetes ever conducted involving more than 5000 patients with type 2 diabetes over a 20 year period. The study examined the effect of tightly controlling blood glucose and blood pressure on the risk of complications. In addition the effectiveness of different therapies was compared.
Patients in the intensive therapy group had a median reduction of 0.9% HbA1c over 10 years and this gave a significant reduction in the risk of complications. Overall there was a 25% risk reduction in microvascular endpoints compared to conventional treatment, most of which was due to fewer cases of retinal coagulation. There was no significant difference between the three intensive treatment groups on microvascular endpoints.1
1. UKPDS 33. Lancet 1998;352:837–853 10 5
Any
Combined
Microvascular
M I
Cataract
Albuminuria
Retinopathy
extraction
UKPDS 33. Lancet 1998;352:837–853

5. HbA1c targets and intensification levels in NICE T2DM
New NICE guidance defines blood glucose targets as
<48 mmol/mol (< 6.5%) for patients on lifestyle or monotherapy with a medication with a low risk of hypoglycemia (metformin)
<53 mmol/mol (<7.0%) for patients on a monotherapy associated with the risk of hypo glycaemia (gliclazide)
Recommends intensification of treatment if HbA1c > 58 mmol/mol (>7.5%)

7. Reminder - medications for type 2 diabetes
Drugs that stimulate insulin secretion:
Sulphonylureas eg. gliclazide
Meglitinides eg. replaglinide
Drugs that influence insulin action
Biguanides - metformin
Thiazolinediones - pioglitazone
Drugs that mimic/ increase GLP-1:
GLP-1 analogues – “tides”
DPP4 inhibitors – “gliptins”
Drugs that promote glycosuria
SGLT-2 inhibitors – “gliflozins”
Insulins

8. Important principles!
Refer to structured education
(Desmond) or give information
about HELP website
Reinforce lifestyle (diet and exercise) at every treatment intensification
Check HbA1c 2-3/12 after an new tablet started and review effectiveness of treatment

9. NICE T2DM 1st line therapy
Metformin:
Renal function:
Don’t start if adjusted eGFR less than 45 and stop if eGFR falls below 30
Caution in those at risk of a sudden change in renal function
Titration:
Start at 500mg OD and increase by 500mg every 2 weeks to a dose of 1g BD
GI side-effects try MR preparation
If BMI < 22 use gliclazide 1st line Consider the need for insulin in a patient with BMI < 22 particularly with symptoms of diabetes Consider an alternative to SU if group 2 driver (hypo risk), frail/elderly or BMI > 35 Alternatives to metformin or SU: DPP4 or pioglitazone SGLT-2 – only if SU or pioglitazone are not appropriate and DPP4 would be used otherwise

10. NICE T2DM 1st Intensification of treatment
The LOCAL RECOMMENDED CHOICE is to add an SU (gliclazide) to metformin NICE provides other options: metformin + pioglitazone metformin + DPP4 An SGLT-2 should only be added to metformin if SU cannot be used or patient has a significant risk of hypoglycaemia
In patients in whom metformin cannot be used: Gliclazide + pioglitazone Gliclazide + DPP4 DPP4 + pioglitazone

11. Pros and cons and rationale for local recommendation to use gliclazide
Cost of oral hypoglycaemic agents per month: Metformin 1g BD = £1.33p Gliclazide 80mg BD = £1.61p Pioglitazone 30mg OD = £1.42p Alogliptin 25mg OD = £26.60p Dapagliflozin = £36.59p
HbA1c reduction (efficacy): Metformin 1-2% Gliclazide 1-2 % Pioglitazone 1-2% Gliptin 0.5 – 1% SGLT – 1% The newer agents have a lower efficacy – consider baseline HbA1c

12. Pros and cons and rationale for local recommendation to use gliclazide
Effect on a patients weight: Metformin – weight neutral Gliclazide – weight gain Pioglitazone – weight gain Gliptin – weight neutral SGLT-2 – weight loss
Hypoglycaemia risk:
Metformin – none/low
Gliclazide – high
Pioglitazone – low
Gliptin – low
SGLT-2 - moderate
The incidence of non-severe hypoglycaemia in T2DM is around 15% and is most associated with SU or insulin tx and longer duration of diabetes

13. T2DM is a progressive disease

14. NICE T2DM 2nd Intensification of treatment
The LOCAL RECOMMENDED CHOICE is insulin if HbA1c > 1% over individualised target
NICE provides other options:
metformin + SU + DPP4
metformin + SU + pioglitazone
metformin + pioglitazone + SGLT-2
metformin + SU + SGLT-2
Pioglitazone contra-indications: Heart failure or h/o heart failure (fluid retention) Bladder cancer or h/o bladder ca Uninvestigated haematuria Liver impairment Pioglitazone cautions: Known CV disease Risk of bladder cancer (smokers) Elderly Risk of fractures (osteoporosis)

15. GLP1 - analogues
NICE recommendation: If patient fails to meet target HbA1c on three oral agents AND: BMI > 35 BMI < 35 with medical reasons why weight gain with insulin would be an issue or occupation Review at 6/12 1% reduction in HbA1c and 3% reduction in weight Local guideline pending