1. Diabetes Update Tara Kadis Lead Diabetes Nurse Specialist
York Teaching Hospitals NHS Foundation Trust

2. Agenda
Overview of the newer therapies’ and their place in the management of type 2 diabetes
Carbohydrate awareness and weight management
Information prescriptions
Overview of insulins and what the patient needs to know in an annual review
Technical advances in diabetes

3. Key Challenges of Type 2 Diabetes
Diabetes is a progressive multi-system disease characterized by:
Declining beta-cell function
Insulin resistance – increasing body weight
Increased risk of cardiovascular disease(including hypertension and coronary heart disease)
Prevalence (England) estimated at 4.7% (2.35m)2
Estimated 92% of diabetes cases are T2D (2.16m)2
41% of patients fail to achieve glycaemic targets (HbA1c <7.5%)2
Failure is associated with devastating and costly complications3
Macrovascular (cardiovascular)4
Microvascular (nephropathy, retinopathy, neuropathy)4
80% of T2DM patients will die of CV disease5
Life lost by a newly diagnosed 60 year old male is 8-10 years6
Mortality attributed to diabetes:6
4.2% deaths in men, 7.7% deaths in women 3 3

4. The trade off !
As diabetes treatments are added to improve glucose control, clinicians & patients face trade-offs such as:
Hypoglycaemia
Weight gain
Complex treatment regimens

5. Weight gain and hypoglycaemia associated with traditional therapies
Delay in progressing with medication
Patients see themselves as failures due to progression of therapies

7. Positive reasons to use this class Reasons not to use this class
Medication choice / decision making support Assess the response of any new class of drug at 3-6 months – if there is no reduction of at least 6mmol/mol (0.5%) in HbA1c in 6 months or if there any concerns regarding side effects stop the chosen medication and move to an alternative class.
Agent
Sulfonylurea
(Gliclazide)
DPP4i
First choice Sitagliptin unless CKD then Linagliptin
Glitazone
(Pioglitazone)
SGLT2i
First choice Dapagliflozin
Positive reasons to use this class
Low cost
Rapid clinical effect
Long established profile
Agent of choice in MODY
Low hypoglycaemia risk
Weight neutral
Licensed in people with CKD (may require dose reduction)
Fewer drug interactions
Reduces insulin resistance
Slower progression to insulin treatment
Weight loss
Reasons not to use this class
Risk of hypoglycaemia (increased in CKD)
Potential need for blood glucose monitoring
Weight gain
Relatively low potency and moderate cost
Slow onset of action
Contraindicated in CCF, LVF
Risk of fractures (women)
Small increase in incidence of bladder cancer)
Moderate cost
If eGFR <60
UTI, genital thrush
Relatively new class – unexpected long term side effects may yet to be recognised
Risk of DKA
Good choice for
Better than metformin for patients with osmotic symptoms
In people whom further weight gain would cause or exacerbate significant problems associated with high body weight
Frail older people
Any person for whom hypoglycaemia is a particular concern
Most likely to benefit people who wish to delay progression to insulin (e.g. group 2 LGV and C1 licence holders)
Obese people
In those whom further weight gain would cause or exacerbate significant problems associated with high body weight
People for whom hypoglycaemia is a particular concern
Monitoring required
Consider home glucose monitoring as per “Who to Test, When to Test” guidance*
Review U & E annually
Review urine dip for blood annually
Review LFT annually
Stop if heart failure/fluid overload develops

8. An Aid to Decision Making in Type 2 Diabetes

9. Newer therapies DPP4 inhibitors – (Gliptins)
GLP-1 – (Glucagon like peptide)
SGLT2 inhibitors – ( Sodium glucose co-transporter 2)
Pioglitazone

10. DPP4 Inhibitors
Sitagliptin, Saxagliptin, Vildagliptin, Linagliptin ,Alogliptin
DPP-4 inhibitors work by blocking the action of DPP-4, an enzyme which destroys the hormone incretin.
Incretins help the body produce more insulin only when it is needed and reduce the amount of glucose being produced by the liver when it is not needed. These hormones are released throughout the day and levels are increased at meal times.

11. DPP4 inhibitors Low risk of hypos Weight neutral
Consider second line if person at risk of hypos or frailty and people in certain jobs e.g. use of heavy machinery.
Reduce dose in renal impairment – Linagliptin first choice in this group
Discontinue if signs of pancreatitis.

12. GLP-1 Effects in Humans GLP-1 secreted upon the ingestion of food
5.Brain:
promotes satiety and reduces appetite4,5
2.α-cell:
suppresses postprandial glucagon secretion1
3.Liver: reduces hepatic glucose output2
DISCUSSION These incretin-based hormone
therapies enhance glucose-dependent insulin secretion; reduce body weight; suppress inappropriate glucagon secretion; regulate gastric emptying; suppress appetite, resulting
in reduced food intake; and promote β-cell neogenesis and
proliferation in animal models. 67
The glucose-lowering effects of GLP-1 receptor agonists are glucose dependent,
which ensures that insulin secretion is coupled to glycemia
and helps to reduce the risk of hypoglycemia. 6
This diagram demonstrates the GLP-1 effects in humans and the role these effects play in normal physiology.
Upon the ingestion of food, plasma glucose levels increase postprandially.
GLP-1 is secreted from intestinal L cells and provides a stimulus to the β-cells to release insulin in a glucose-dependent manner. When plasma glucose levels return to normal, the action of GLP-1 decreases1.
GLP-1 also suppresses glucagon levels that are inappropriately elevated in patients with type 2 diabetes1. Lower glucagon levels leads to decreased hepatic glucose output2.
In the stomach, GLP-1 slows the rate of gastric emptying, which reduces the rate at which meal-derived glucose appears in the circulation3.
In the brain, GLP-1 promotes satiety and reduces appetite, which leads to a feeling of fullness and a reduction in food intake4,5.
All these actions help maintain overall glucose homeostasis.
1Nauck MA, et al. Diabetologia 1993;36:741–744
2Larsson H, et al. Acta Physiol Scand 1997;160:413–422
3Nauck MA, et al. Diabetologia 1996;39:1546–1553
4Flint A, et al. J Clin Invest 1998;101:515–520
5Zander et al. Lancet 2002;359:824–830.
1.-cell: enhances glucose-dependent insulin secretion in the pancreas1
4.Stomach: slows the rate of gastric emptying3
Adapted from 1Nauck MA, et al. Diabetologia 1993;36:741–744; 2Larsson H, et al. Acta Physiol Scand 1997;160:413–422; 3Nauck MA, et al. Diabetologia 1996;39:1546–1553; 4Flint A, et al. J Clin Invest 1998;101:515–520; 5Zander et al. Lancet 2002;359:824–830. 12 12

13. GLP-1 Usually add on to oral following Step 3 in algorithm
Poor diabetes control (HbA1C ≥ 58mmol/mol )
BMI >35.0kg/m²
Can be given:
X 2 injections a day
X 1 injection a day
X 1 injection a week

14. GLP-1 Lixisenatide (Lyxumia) Liraglutide (Victoza) Exenatide (Byetta)
Once weekly exenatide (Bydureon)
Once weekly dulaglutide (Trulicity)

15. Contraindications of GLP-1
Pregnancy/breast feeding
Type 1 Diabetes (used for weight management – specialist initiation)
Pancreatitis
Risk of hypoglycaemia in combination with sulfonylurea
Can now be used in eGFR 15 (Liraglutide)

16. Pros/cons Weight loss Minimal titration
Less considerations re driving/employment
Side effects
Contra Indications
NICE recommendations for continuation –
11mmol/mol drop in HbA1c and 3% weight loss by 6 months
Follow- up

17. SGLT-2 inhibitors Newest new class of oral hypoglycaemic.
They lower plasma glucose by inhibiting the reabsorption of glucose from the glomerular filtrate in the nephron – increasing urinary glucose excretion.
Eliminates 50 to 80 g of glucose/day (200 to 320 Kcal/d

18. Increased urinary glucose excretion
SGLT2
SGLT2
Dapagliflozin
Proximal tubule
Glucose
filtration
Increased urinary glucose excretion
1. FORXIGA Summary of Product Characteristics

19. dapagliflozin, canagliflozin, empagliflozin
SGLT-2 inhibitors
dapagliflozin, canagliflozin, empagliflozin
Daily oral tablet
Low hypoglycemic risk if used as add on to metformin
Can be used with insulin (lowers insulin dose requirement)
Used to aid weight loss
Only suitable with eGFR >60
Main side effect increased risk of UTI
DKA risk – not currently used in Type 1 diabetes

20. Pioglitazone Increases insulin sensitivity Reduces insulin resistance
Slows progression to insulin
Contraindicated in CCF, LVF,
Small increased risk of bladder cancer and risk of fractures in women
Most benefit to wishing to delay progression to insulin

21. Case Study….Peter 62 years old Type 2 Diabetes for 9 months
HbA1c 68 mmol/mol
BMI 30
Office job but drives to work
Current meds:
Metformin 1G BD
Atorvastatin 20mgs
What treatment options should we consider next?
Read the above case study to the group

22. Case Study….Peter SGLT-2 ? Gliclazide? DPP-4 inhibitor?
Pioglitazone ? The Answer is …………………………………?.
Read the above case study to the group

23. Overview of current insulin regimes & education required
Insulin management
Overview of current insulin regimes & education required

24. When to initiate insulin.
In Type 2 Diabetes when
other measures fail to keep desired HbA1c <58 mmol/mol
Max dose of tolerated treatment – usually triple therapy and/or other Injectables
Consider in dual therapy when significant hyperglycaemia in preference to adding further drug to control blood glucose unless true justification not to.
OHA not tolerated/contra-indicated
Symptoms related to poor glycaemic control
Other medication causing temporary raise in blood glucose levels e.g. steroids

25. Before insulin therapy
Reinforce dietary advice and discuss lifestyle issues and employment i.e. smoking and physical activity
Check ability to administer own insulin / carers district nurse involvement
Patients should be taught home blood glucose monitoring advice to monitor blood glucose at different times.

26. Structured programme Structured education
Importance of glucose self monitoring
Dose titration to target
Dietary understanding, carbohydrate awareness
Management of hypoglycaemia
Management of acute changes in glucose control
Driving

27. Which? Basal Bolus Regime Basal Insulin
with oral hypoglycaemic agents
Pre-mixed insulin with oral hypoglycaemic agents
Basal Bolus Regime
First line choice
Overweight BMI >26
Reluctance to start insulin
Unable to inject themselves
HbA1c > 75 mmol/mol (9%)
Regular lifestyles
Symptomatic
Carbohydrate consistency
On daily/bd insulin regimes without optimal control
Requiring flexibility due to an erratic lifestyle
Shift work
Regular travel across time zones
Regular sport
To optimise blood glucose control because of complications
We have a local pathway for insulin initiation. I'm going to review the different insulin regimes and offer some practical advice on which regime may fit different patients

28. Basal Human Insulin NPH first line choice (NICE)
Starting with a dose usually before bed
Titrate in line with fasting blood glucose levels
Continue with OHA to help control day time blood glucose levels
May be given twice daily if blood glucose levels indicate it
Associated with less weight gain and hypos
Basal insulin in usually the first line choice

29. Basal Human Insulin Humulin I Insulatard Insuman Basal
Human basal have a peak of insulin which tends to work overnight to help correct the a patients fasting blood glucose level. Examples of these insulin's are humulin I, insulatard and insuman basal 29

30. Getting started
Commence once daily basal insulin in the evening - 10 units start dose
Continue other oral hypoglycaemic agents
Teach the patient to titrate insulin dose by units every days
Aim for fasting blood glucose of 5 – 8 mmol/l

31. What are the choices? Humulin I – (first choice) Insulatard –
Kwikpen
3ml Cartridges ( Savvio Pen)
10ml Vial
Insulatard –
Innolet
3ml Cartridges ( Novopen 5)
10ml vial
Insuman Basal
Solostar pen
3ml Cartridges (AllStar pen)

32. Basal Analogue Lantus, Levemir, (Toujeo, Tresiba) Considerations:
If person needs assistance from a carer or healthcare professional to inject insulin and therefore reduce the frequency of injections
Hypoglycaemia is a problem with NPH
To add to the confusion we have another basal insulin to consider the basal analogues
Analogues insulin's are specifically designed to work in a specific way. The basal analogues have a flat profile, which makes it a better choice for patient having problems with hypos on human basal insulin
Lantus is the longer acting of the two and can be given once and a convenient time if assistance if required from carers of HCP

33. What are the choices? Abasaglar (first choice) Lantus Solostar Levemir
3ml Cartridges ( Savvio pen)
Kwikpen
Lantus Solostar
3ml Cartridges ( pen)
10ml Vial (use when needing District nurse administration)
Levemir
Flexpen
Innolet
3ml Cartridge ( Novopen 5)
Toujeo
Solostar pen
Tresiba 100 / 200 (initiated in specialist care)
Flextouch pen

34. Human Basal V Basal Analogue
Basal Human insulin
Basal analogue
This slide shows the difference between a human basal insulin and a basal analogue. Notice the flat profile of the basal analogue compared the slight peak of the human basal insulin

35. Example algorithm for titrating human basal insulin from a randomised controlled trial
Exceptions to algorithm:
No increase in dose if fasting plasma glucose ≤4 mmol/L is documented at any time in the preceding week
Small insulin dose decreases (2-4 unit/day per adjustment) are allowed if severe hypoglycaemia (requiring assistance) or a fasting plasma glucose of 3.1 mmol/L is documented in the preceding week
Yki-Jarvinen H et al (2006) Diabetologia 49: 442–51

36. Titration guidelines Fasting blood Glucose Action >10
mmol/l
Action
>10
Increase by 4 units
8 – 10
Increase by 2 units
5 - 7
No change
3 - 5
Reduce by 2 units
<3
Reduce by 4 units
Titration of both insulin's remains the same using the Patients FBG as a marker to titrate again.
Once FBG levels are stable it is a good idea to get the patient to test some reading during the day. I usually ask them to alternate the lunch/evening meal and bed readings through the week to assess their control.

37. Common options for intensifying basal insulin regimens
Switch to twice-daily premixed insulin
Add once-daily prandial insulin with the largest meal (basal-plus)
Additional prandial injections can be added
Add three times daily prandial insulin with meals (basal-bolus)
Intensify with an additional injection
Adapted from Barnett A et al (2008) Int J Clin Pract 62: 1647–53

38. Twice Daily Biphasic Human insulin
Consider if HbA1c ≥ 75mmol/mol
If unable to achieve control on basal insulin
Regular lifestyle – consistent carb intake
Increased risk of weight gain / hypoglycaemia than with basal insulin
NICE recommend Human Mixtures
The next step from a basal insulin is to move to a twice daily pre-mixed human insulin such as humulin M3, insuman combo in different concentrations.
The number represents the amount of quick acting insulin in the mixture. Eg M3 30% QA and 70%
Twice daily human pre-mixed insulin are generally used first line when converting to a mixed insulin.

39. BD Pre Mixed Human Insulin6 7 8 9 10 11 12 1 2 3 4 5
Breakfast
Lunch
Evening Meal
Sleep 39

40. What are the choices? Humulin M3 (first choice)
Kwikpens (disposable device)
3ml cartridge
10ml vial
Insuman comb 15 / 25 / 50
3ml cartridge (AllStar pen)
Solostar pen (disposable device) 25 mix only

41. Getting started In insulin naive patients usually start with:
12 units am & 8 units pm or
16 units am & 12 units pm in overweight patients
If switching from once daily basal insulin:
Consider reducing dose by %
2/3rds of dose AM 1/3 of dose PM
Need to be injected 30 – 40 mins pre meal
Continue with metformin
Continue the sulfonylurea initially, but review and discontinue if hypoglycaemia occurs.

42. When to consider an Analogue mix?
Analogue mixtures provide a quicker onset of action and offer some advantage in people with post prandial meals rises.
May also help prevent hypoglycaemia in between meals due to quicker action of rapid insulin
Injection timing an issue

43. Insulin Analogue Mixtures
Inject twice daily, within 0 to 15 minutes before or after meals.
Useful in rapid post prandial rise as works quicker
Humalog Mix25, Mix50
Novomix 30
Analogue mixtures provide a quicker onset of the quick acting component of the insulin mixture and offer some advantage in people with post prandial meals rises.
Due to the onset of the quick acting part of the insulin there is a slight increase in hypos. 43

44. What are the choices? Humalog Mix 25, 50 Novomix 30 Kwik pen
3ml cartdriges ( Savvio pen)
10ml Vial (Humalog Mix 25 only)
Novomix 30
Flexpen
3ml Cartridges (Novopen 5)

45. Basal plus
Addition of prandial rapid acting insulin to basal insulin (Humulin I,Insulatard, Insuman basal, Insulatard)
Give rapid dose with main meal or highest post meal blood glucose level
Stepwise approach leading to injection with each meal
Usual starting dose 6 units
NovoRapid / Humalog / Apidra
Continue on basal insulin

46. What else do we need to know?
Blood glucose monitoring
Hypoglycaemia management
Illness management / sick day rules
Injection rotation
Driving
Identification / insulin passport
INSULIN TITRATION guidelines.

47. Blood Glucose Monitoring
Individual assessment based on
Number of injections
Occupation / driving
Treatment
Consider post meal in patients who you suspect of post prandial hyperglycaemia.
Meter standardization in Type 2 diabetes
Who to test, when to test

48. Treatment of hypoglycaemia
Blood glucose below 4 mmol/l
4- 5 glucotabs
3-4 jelly babies
1x mini can of coca cola.
RECOVERY 10 – 15 MINS
Longer acting Carbohydrate
1 portion fruit / 2 plain biscuits / 1 slice of bread.

49. Sick day rules. Don’t stop insulin!
Blood glucose mmol/L = 2 units extra
Blood glucose mmol/L = 4 units extra
Blood glucose more than 22 mmol/L 6 units extra
(if on over 50 units a day double the adjustments)
Increase blood glucose monitoring usually every 4 hours
Drink fluids – 100mL/hour prevent dehydration
Consider stopping orals if dehydrated
Managing diabetes during intercurrent illness in the community February 2013 NHS Diabetes

50. Travel Carrying insulin / frio packs Travel letter Time zones
Foot care
Identification
Insurance

51. Needle size 4 or 5 mm needle length of choicex

52. Lipohypertrophy

53. Lipohypertrophy

54. DVLA requirements
Specific to insulin treated patients with group 1 entitlement
Must have awareness of hypoglycaemia
no more than 1 episode of severe hypoglycaemia while awake in the preceding 12 months or the most recent episode occurred more than 3 months ago
There must be appropriate blood glucose monitoring
Must not be regarded as a likely source of danger to the public while driving
The visual standards for acuity and visual field must be met.

55. DVLA requirements
blood glucose testing no more than 2 hours before the start of the first journey and
every 2 hours while driving
Continuous glucose monitoring systems (CGMS)
Because these systems measure interstitial glucose, drivers must also monitor blood glucose levels as outlined immediately above

56. Group 2 –Bus & Lorry Licensing
requires the applicant’s usual doctor who provides diabetes care to undertake an annual examination including review of the previous 3 months of glucose meter readings
require an examination to be undertaken every 12 months by an independent consultant specialist in diabetes if the examination by their usual doctor is satisfactory
the license application process cannot start until an applicant’s condition has been stable for at least 1 month

57. Titration guidelines Fasting blood Glucose mmol/l Action >10
Increase by 4 units
8 – 10
Increase by 2 units
5 - 7
No change
3 - 5
Reduce by 2 units
<3
Reduce by 4 units
Titration of both insulin's remains the same using the Patients FBG as a marker to titrate again.
Once FBG levels are stable it is a good idea to get the patient to test some reading during the day. I usually ask them to alternate the lunch/evening meal and bed readings through the week to assess their control. 57

58. What to include in the annual review!
Understanding of:
Hypoglycaemia status and management
Sick day rules
Check for lipos
Injection technique – are they reusing needles !
Sharps removal
When to seek help and by whom
Dietary update
Driving status and DVLA recommendations ID
How to titrate doses

59. Patient information leaflets
Sick day rules for Type 1
Sick day rule for Type 2
Travel
Management of hypoglycaemia
Diabetes and Activity

60. Freestyle libre
FreeStyle Libre® measures glucose levels from a sensor applied to the skin as an alternative to routine finger-prick blood glucose testing.
It can also indicate glucose level trends over time. Glucose readings can be seen anytime by scanning the sensor with a Libre reader or an smart mobile device. The glucose readings can be downloaded to look at in more detail at home which can help with insulin adjustments.
Need to refer patient into Specialist care for assessment and review of treatment

61. Patient criteria ? Patient has Type 1 diabetes and:
Meet current NICE criteria for insulin pump therapy (HbA1c ≥69.4 mmol/mol or disabling hypoglycaemia as described in NICE TA151) where a successful trial of freestyle Libre may avoid the need for pump therapy.
Recently developed impaired awareness of hypoglycaemia.
Two or more admissions per year with diabetic ketoacidosis or hypoglycemia.
Patient who have considerable difficulties in finger prick testing due to physical limitation.
Patient with functional impairment that impact on their ability to interpret standard finger prick testing results.
Pregnant women with Type 1 DM or Type 2 DM on basal bolus insulin regime and in women who are trying to conceive. ( Women with gestational diabetes are excluded unless the above criteria are met)

62. Diabetes Specialist Outreach Team (DSOT)
Department of Health and Social Care – sustainable transformation funding to improve the care of people with diabetes in the Scarborough and York area.
Specifically, for those
at high risk of diabetes complications despite accessing usual care or
disengaged from usual services - people that are hard-to-reach.

63. Transformation -2 year project
National Diabetes audit – high risk for CVD
Hard to reach/engage people with DM
Care homes
Recurrent admissions with DKA/Hypos
New model- MDT includes psychologist and social worker
Focus also on diabetes medicines optimization, BP and Cholesterol reduction

64. Case finding will be through:
primary care searches and medicines-management initiatives based on NICE targets
hospital data searches
direct referral from secondary care

65. How to contact us Scarborough Diabetes Nurses:
Task –’community diabetes nurses’

66. Thankyou for listening
Any Questions?