Insulin Speakers Dr Roni Saha , Consultant Diabetologist, St Georges - - PowerPoint PPT Presentation

Insulin

Speakers Dr Roni Saha, Consultant Diabetologist, St George’s Hospital Lisa Egan, Community Diabetic Specialist Nurse, CLCH In collaboration with the Health Innovation Network

Agenda

TIME ACTIVITY FORMAT 12.30 – 13.00 LUNCH 13.00 – 13.05 Introductions Presentation The Diabetes problem… Presentation + interactive The right time for insulin; an evidence & case-based discussion Presentation Myths and barriers Insulin Management: Key Facts Insulin initiation The right insulin Insulin types & regimens Insulin dose adjustment Presentation Cases, conclusions & questions Presentation + interactive 14.55 – 15.00 Evaluation Sheet Completion Attendees

Introductions

Putting faces to names: Dr Roni Saha (Consultant Diabetologist, SGH) Dr Sachin Patel (West Wandsworth Diabetes GP Lead) Raj Dhir (Senior Prescribing Advisor, Wandsworth CCG) Diabetes Specialist Nurses (CAHS and QMH) Vedrana van Rheede (Project Manager, GP Federation) Pamela Wilson (Coordinator, GP Federation)

Diabetes Service Improvement in Primary Care

• Wandsworth CCG has commissioned BHCIC/GP Federation to

undertake a review of diabetes care, based on the success of the 2017/2018 Diabetes deep dives

• Overarching aim is to review and improve service pathways as

an opportunity to improve clinical outcomes for patients with Diabetes

Elements of the review

• Primary Care activity including Deep Dive

visits

• Clinical Audit of Diabetic patients (as under

PACT service req. 10)

• Education needs
• Outpatient activity review
• Education events

Diabetes related activities and events

• PACT Diabetes Clinical Audit (part of PACT Service Specification

req.10) Part 1 audit due 31st July 2018.

• 20th September 2018 Event focusing on the initial audit and
• utcomes
• Part 2 audit due end January 2019
• Third Diabetes related event to be confirmed between February-

March 2019.

The Diabetes Problem…

DIAB-1150856-0000

HYPERGLYCAEMIA

Islet cell dysfunction

• 3. Pancreatic

beta cells Decreased insulin secretion Pancreatic alpha cells Excessive glucagon secretion

Insulin resistance

• 1. Inzucchi SE. JAMA 2002;287:360–372.
• 2. Porte D Jr, Kahn SE. Clin Invest Med 1995;18:247-254.
• 2. Liver

Increased glucose production

• 1. Peripheral tissues

Decreased glucose uptake Increased lipolysis

Combined islet cell dysfunction and insulin resistance

Pathophysiology of type 2 diabetes involves three core defects and multiple organ systems

DIAB-1150856-0000

The ominous octet: Multiple organ and hormone dysfunctions contribute to type 2 diabetes

• 1. DeFronzo RA (2009) Diabetes 58: 773–95

Chronic hyperglycaemia

β

α

Glucagon secretion Lipolysis Glucose reabsorption Insulin secretion Incretin effect Glucose uptake Glucose production Neurotransmitter dysfunction

DIAB-1150856-0000

11

Islet cell dysfunction in type 2 diabetes

Normal

Alpha cells

Glucagon

Beta cells

Insulin

Cell type Hormone Physiological action Abnormality in type 2 diabetes Alpha cell

Glucagon

Stimulates hepatic glucose output to avoid hypoglycaemia Glucagon not suppressed after eating; worsens hyperglycaemia Beta cell

Insulin

Increases glucose uptake in the liver and peripheral tissues Inadequate and delayed insulin response contributes to hyperglycaemia

• 1. Porte D Jr, Kahn SE. Clin Invest Med 1995;18:247-254.
• 2. Rhodes CJ. Science 2005; 307:380-384.
• 3. Gerich JE. International Rev Phys 1981; 24:243-275.
• 4. Müller WA et al. N Engl J Med 1970: 283:109-115.

Illustration reproduced with permission from reference 2.

Type 2 diabetes

• Fewer islets
• Fewer beta cells per islet

Pancreas Pancreas

DIAB-1150856-0000

Diabetes is a chronic and progressive disease

▪ Decline in insulin sensitivity, β-cell function and incretin effects all occur prior to development

• f overt type 2 diabetes

Years

• 15
• 10
• 5

5 10 15 20 25 30 200 150 100 50 250 Insulin resistance Insulin level Relative Amount β-cell function Diagnosed diabetes

Diabetes Onset

350 300 250 200 150 100 Postmeal glucose Fasting glucose Glucose (mg/dL) 50 Prediabetes ≥50% loss of β-cell function at diagnosis*

IGT=impaired glucose tolerance.

• 1. Kendall DM et al (2009) Am J Med 122: S37–50; 2. DeFronzo RA (2009) Diabetes 58: 773–95;
• 3. Holman RR (1998) Diab Res Clin Prac 40(suppl):S21–5

Adapted from Kendall DM et al (2009) Am J Med 122:S37–50. *By the time diabetes is clinically diagnosed, β-cell function may be reduced by ≥50%; subjects in the upper tertile of IGT are near-maximally insulin resistant and have lost more than 80% of their β-cell function.1–3 Representative depiction of the natural progression of type 2 diabetes (time course and function).1

• 1. UKPDS (1998) Lancet 352: 837–53; 2. Holman RR et al (2008) N Engl J Med 359: 1577–89; 3. Gerstein HC et al (2008) N Engl J Med 358: 2545–59; 4. ACCORD Study Group (2011) N

Engl J Med 364: 818–28; 5. Ismail-Beigi F et al (2010) Lancet 376: 419–30; 6. Patel A et al (2008) N Engl J Med 358: 2560–72; 7. Zoungas S et al (2014) N Engl J Med 371: 1392–406; 8. Duckworth W et al (2009) N Engl J Med 360: 129–39; 9. Hayward RA et al (2015) N Engl J Med 372: 2197–206

Impact of intensive therapy for diabetes: Summary of major clinical trials

Study Microvascular Macrovascular Mortality UKPDS1,2

     

ACCORD3–5

 NR    

ADVANCE6,7

 *    

VADT8,9

 NR    

Long-term follow-up Initial trial

*End-stage renal disease. ACCORD=Action to Control Cardiovascular Risk in Diabetes; ADVANCE=Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation; NR=not reported; UKPDS=UK Prospective Diabetes Study; VADT=Veterans Affairs Diabetes Trial.

HbA1c individual target setting

At diagnosis On no / one oral agent

48mmol/mol 6.5%

NICE NG28 (2015)

Considering a second

• r third agent

58mmol/mol 7.5%

[UKPDS: mean HbA1c in control group - 63mmol/mol NICE QS6 (offer dual therapy)

NICE NG28 (2015) Currie et al. (2010) Survival as a function of HBA1c in people with type 2 diabetes: a retrospective analysis, Lancet, 375: 481-489 NHS England measure

Functionally dependent, frail, limited life expectancy History of severe hypoglycemia Advanced microvascular or macrovascular complications Extensive comorbid conditions

58- 64mmol/mol 7.5-8%

• r higher

ADA/EASD position statement update (Inzucchi et al. 2015) Diabetes UK steering group (2013). Clinical care recommendations: end of life diabetes care Abdelhafiz & Sinclair (2016) Frailty & hypoglycaemia in older people with type 2 diabetes, J of Diabetes Nursing 20(9): 330-331

Discuss with the individual

53mmol/mol 7%

UKPDS (1998): mean HbA1c in the intensive group 53mmol/mol Preferred target if taking sulfonylureas SIGN (2010) ADA/EASD position statement update (Inzucchi et al. 2015) NICE NG28 (2015)

Over time

Suggested Goals for Glycemic Treatment in Patients with Type 2 Diabetes.

Glycaemic goals for people with T2DM

The Right Time for Insulin: An Evidence & Case Based Discussion

Some patients with T2DM may not benefit from insulin

• Some obese people in whom insulin treatment can lead to further weight gain,

with little or no improvement in HbA1c

• People whose oral anti-diabetes treatment regimen could be improved
• Elderly people with a short duration of diabetes and no symptoms of

hyperglycaemia

• People with other physical or mental health problems in whom the potential

benefits of insulin treatment may not outweigh the potential risks

• Occupational related
• Royal College of Nursing (2007) Starting insulin treatment in adults with type 2 diabetes. RCN guidance for nurses. Available at: http://tiny.cc/4aktx(accessed 04.02.2013)

Insulin use in Type 2 Diabetes

• UKPDS - Type 2 diabetes is a progressive condition1
• At diagnosis, beta cell function may be reduced by 50%. This decline continues regardless
• f therapy2
• Some patients will progress to insulin therapy more quickly than others, depending on

duration of diagnosis

1. UKPDS (49).Jama 1999;281(21):2005-12 2. Williams G & Pickup JC. Handbook of Diabetes, 3rd Ed. 2004

Question: What target would you recommend for this person?

50-year-old lady, 10-year history of type 2 diabetes, with an HbA1c level of 8.6% (70 mmol/mol) on max metformin, sulphonylurea and GLP-1 agonist 1.<6.5% (<48 mmol/mol) 2.<7.0% (<53 mmol/mol) 3.<7.5% (<58 mmol/mol) 4.<8.0% (<64 mmol/mol) 5.<8.5% (<69 mmol/mol) 6.I’m happy with her current HbA1c level 7.Something else

Question: What target would you recommend for this person?

50-year-old lady, 10-year history of type 2 diabetes, with an HbA1c level of 8.6% (70 mmol/mol) on max metformin, sulphonylurea and GLP-1 agonist 1.<6.5% (<48 mmol/mol) 2.<7.0% (<53 mmol/mol) 3.<7.5% (<58 mmol/mol) 4.<8.0% (<64 mmol/mol) 5.<8.5% (<69 mmol/mol) 6.I’m happy with her current HbA1c level 7.Something else

53mmol/mol

Question: What target would you recommend for this person?

85-year-old lady, 10-year history of T2 diabetes, with an HbA1c level of 8.6% (70 mmol/mol). She has heart failure, retinopathy and CKD 3b on MF 1g bd, Alogliptin 12.5mg od and GC 80mg bd

1.<6.5% (<48 mmol/mol) 2.<7.0% (<53 mmol/mol) 3.<7.5% (<58 mmol/mol) 4.<8.0% (<64 mmol/mol) 5.<8.5% (<69 mmol/mol) 6.I’m happy with her current HbA1c level 7.Something else

eGFR=estimated glomerular filtration rate.

Question: What target would you recommend for this person?

85-year-old lady, 10-year history of T2 diabetes, with an HbA1c level of 8.6% (70 mmol/mol). She has heart failure, retinopathy and CKD 3b on MF 1g bd, Alogliptin 12.5mg od and GC 80mg bd

1.<6.5% (<48 mmol/mol) 2.<7.0% (<53 mmol/mol) 3.<7.5% (<58 mmol/mol) 4.<8.0% (<64 mmol/mol) 5.<8.5% (<69 mmol/mol) 6.I’m happy with her current HbA1c level 7.Something else

eGFR=estimated glomerular filtration rate.

58-64 mmol/mol

Blood Glucose Management in Adults with Type 2 Diabetes - Metformin Tolerant

After diagnosis initiate lifestyle changes (smoking cessation, healthy eating, weight control & increased physical activity) and refer to structured education - DESMOND. Consider a bariatric surgery referral in appropriate patients. At ALL appointments reinforce advice on diet, lifestyle and adherence to drug treatment. Check HbA1c 3 months after ANY therapy change. Move to next step of therapy if target is not achieved. Discuss/refer to diabetes team if clinical concern at any stage FIRST INTENSIFICATION: If HbA1c rises to ฀58 mmol/mol* (7.5%) add in 2nd line therapy. FIRST LINE THERAPY - Metformin (MONOTHERAPY)

Start at a dose of 500mg daily with food. Increase by 500mg every 2 weeks to reach a target dose of 1g twice daily or maximum tolerated dose Before starting metformin, check corrected eGFR and note renal precautions (see box overleaf) If GI intolerance occurs, try metformin modified release or reduce dose to previously tolerated dose Aim for HbA1c level of 48mmol/mol (6.5%) If the person is symptomatically hyperglycaemic, consider insulin or an

• SU. Review treatment when blood

glucose control has been achieved

Blood Glucose Management Targets

Involve adults with type 2 diabetes in decisions about their individualised HbA1c targets Agree on individualised HbA1c target based on the person needs and circumstances including preferences, comorbidities, risks from polypharmacy and tight blood glucose control, ability to achieve longer term reduction benefits, disease duration, life expectancy and motivation. Support them to achieve the target and maintain it unless they experience adverse effects (including hypoglycaemia), or their efforts to achieve their target impair their quality of life Consider relaxing the target HbA1c level as appropriate in people who are older or frail, people with reduced life expectancy, for people in whom tight blood glucose control poses a high risk i.e. people at risk of falling, people who drive or operate machinery as part of their job and those with significant comorbidities. If they achieve an HbA1c level lower than their target with no hypoglycaemia, encourage them to maintain it. Be aware of other possible reasons for a low HbA1c level e.g. declining renal function, sudden weight loss. Measure HbA1c levels at 3 - 6 monthly intervals, until it is stable or unchanging. 6 monthly intervals are recommended once HbA1c level and drug treatment is stable. Add sulfonylurea (SU) Gliclazide is the preferred SU locally** Add Gliptin (DPP-4 inhibitor) Alogliptin is the preferred gliptin locally** Add pioglitazone Add in either: Gliptin (Alogliptin) or Pioglitazone or SGLT-2i (Empagliflozin) Add in either: Gliclazide Add in either: Gliclazide or SGLT-2i (Empagliflozin) Add in either: Gliclazide Pioglitazone GLP-1 agonists are recommended as an option with metformin and gliclizide when oral triple therapy is not effective/not tolerated/contraindicated for adults who: Have a BMI ฀3 5kg/m2 in those of European descent (adjust accordingly for ethnicity)*** and specific psychological or other medical problems associated with obesity OR Have a BMI <35kg/m2 and for whom insulin therapy would have significant occupational implications, or weight loss would benefit other significant

• besity related co-morbidities.

Therapy must be reviewed at 6 and 12 months Treatment should only be continued after 6 months if reduction of 1% (11mmol/mol) in HbA1c is achieved and a weight loss of 3% of initial bodyweight.

Insulin Initiation

Refer to local community / hospital diabetes team for insu- lin initiation through a structured programme. Continue to offer metformin for people without contraindications or intolerance. Review the continued need for other blood glucose lowering therapies. NB: In line with NICE, human isophane (NPH) insulin (Insulatard, Humulin I and Insuman Basal) is recommended as first line basal insulin. Long lasting insulin analogues should be reserved for patients meeting criteria defined by NICE Insulin is eventually needed for many, due to the progres- sive nature of type 2 diabetes; initiation of insulin therapy should not be delayed. Note: Combination use of insulin and a GLP-1 agent can only be initiated by specialist diabetes teams with

• ngoing support from a consultant-led team.

If HbA1c rises to 48mmol/mol (6.5%) despite 3 months of lifestyle interventions, offer first line therapy with metformin

*other individual target **this local recommendation must only be taken into account after a patient & prescriber have discussed all treatment options & only if they have no preference about which medicine they want to use *** adjust accordingly for people from Afro-Caribbean. Asian and other minority ethnic groups

Drug Treatment Choice & Review

Base the choice of drug treatment (s) on: Effectiveness, safety - (see MHRA guidance), tolerability, the persons individual clinical circumstances, comorbidities, preferences, needs, licensed indications, and cost (if two drugs in same class appropriate - select

• ne with lowest acquisition cost)

Ensure renal & hepatic monitoring for individual drugs is taken into consideration - see SPC Reassess the person’ s needs & circumstances at each review and stop any medicines that are not effective

Self-Monitoring Blood Glucose

Do not routinely offer blood glucose self-monitoring for adults with type 2 diabetes unless: The person is on insulin or On oral medication likely to cause hypoglycaemia e.g. SU while driving or operating machinery or There is evidence of hypoglycaemia or The person is pregnant, or planning to become pregnant or Unless clinically requested by a specialist

SECOND LINE THERAPY - DUAL THERAPY (Metformin + either of the following classes of drugs below)

Provide and explain the NICE ‘ Patient Decision Aid’ (PDA) document to help adults with type 2 diabetes make informed decisions about taking a second medicine for blood glucose control. Tailor the information to reflect the person’ s clinical circumstances as necessary (e.g. if certain medicines are contraindicated) Review treatment plan and reinforce advice about diet, lifestyle & adherence to drug treatment Aim for HbA1c level of 53 mmol/mol (7.0%)* Add SGLT- 2i inhibitor (SGLT-2i) Only to be used if SU not tolerated/contraindicated

• r person at significant risk of hypoglycaemia or its

consequences. Empagliflozin is the preferred SGLT-2i locally**

Do not initiate if eGFR <60ml/min

OR OR OR

SECOND INTENSIFICATION: If HbA1c rises to ฀58 mmol/mol* (7.5%) add in 3rd line oral therapy or insulin

OR OR OR

THIRD LINE THERAPY

Produced: January 2017 Review Date : January 2019

Aim for HbA1c level of 53mmol/mol (7.0%)*

Jay, age 48

Diagnosed with type 2 diabetes in 2005. Metformin started in 2007 (1g BD), Gliclazide 160mg bd by 2009, Alogliptin 25mg added in 2014

HbA1c history: 2010 – 2013 < 58mmol/mol 2014: 69mmol/mol 2015: 61mmol/mol 2017: 72mmol/mol BMI improvement from 27.3 to 24.4 eGFR > 82 Admits to missing evening Metformin couple

• f times a week but generally compliant.

Some tiredness and occasional osmotic symptoms

Hba1c target?

Jay, age 48

Diagnosed with type 2 diabetes in 2005. Metformin started in 2007 (1g BD), Gliclazide 160mg bd by 2009, Alogliptin 25mg added in 2014

HbA1c history: 2010 – 2013 < 58mmol/mol 2014: 69mmol/mol 2016: 61mmol/mol 2018: 72mmol/mol BMI improvement from 27.3 to 24.4 eGFR > 82 Admits to missing evening Metformin couple

• f times a week but generally compliant.

Some tiredness and occasional osmotic symptoms

INSULIN

Myths and Barriers

Why is Insulin Often Delayed?

• Barriers + concerns by patients?
• Barriers + concerns by HCP’s?
• Newer injectable GLP-1 analogues as an alternative

to insulin?

Patients

Potential Barriers/Concerns:

• Try harder with diet and exercise
• Sense of personal failure
• Injection related anxiety
• Fear of restricted lifestyle
• Lack of positive gain
• Fear of hypoglycaemia
• Fear of weight gain
• Perception that insulin initiation is

associated with complications e.g. blindness How Might These be Overcome?

• Avoid colluding with pt, explain

progression of T2DM, HbA1c targets

• Avoid ‘you have failed on OHA’s’, reassure

they have not failed, discuss possible future insulin therapy at diagnosis

• Show needle size / dummy injection
• Once daily regimens + OHA’s
• Improvement in symptoms
• Reduction in micro-vascular complications

(UKPDS)

• Severe hypo rare in T2DM. Consider long-

acting analogue as per NICE guidance.

• Importance of diet and exercise
• Complications may have already been

present, explain progressive nature of T2DM

Healthcare Professionals

Potential Barriers/Concerns

• Lack of time to counsel reluctant patients
• Some patients may not manage due to:-
• fear of needles + ability to self inject
• don’t comply with current medication
• Concerns about weight gain
• Concerns about hypos
• Unfamiliarity of when to consider insulin

therapy

How Might These be Overcome?

• Use of open ended questions
• Understanding health beliefs
• Demonstrate pen device and needle length
• Explain it’s a once daily injection before

bed

• Importance of diet + exercise
• Aim to minimise weight gain with once

daily regimen with Metformin

• Severe hypoglycaemia rare in T2DM.

Consider long-acting analogue as per NICE guidance.

• Consider insulin as soon as Hba1c

>58mmols/mol on max OHA, instead of delaying until Hba1c much higher

Insulin Management: Key Facts

How to start insulin

Considerations Before an Insulin Start

• Check occupation is no contra-indication to insulin eg; armed forces,

emergency services, train/tube driver

• Is the patient on maximum OHAs?
• Are they taking their OHAs regularly/correctly?
• Are they monitoring their blood glucose?
• Eating patterns, diet and alcohol?
• Level of physical activity?
• Re-assess psychosocial issues and lifestyle changes
• Do they understand their condition?

Introducing Insulin…

• Address the patient’s concerns, use open ended questions ..
• Explain the reasons and benefits for starting insulin

(symptomatic patients will often feel much better)

• Usually start on just one injection a day
• Let the patient ‘play’ with a pen device/do a dummy injection
• Diet, activity, blood glucose testing and other medication is still

important as insulin alone will not control diabetes

The Insulin Start

• Refer patient into Tier 2 clinic
• Patient needs 3 separate appointments
• Insulin Assessment

= 30 mins

• Insulin Start

= 45 mins

• Insulin Review

= 45 mins

Assessment for Insulin Start

• Discuss with patient why insulin therapy is now needed and obtain verbal consent
• Establish any symptoms of hyperglycaemia
• Urinalysis for glucose / ketones
• Discuss possible medication changes
• Show pen devices and needle size to allay fears
• Encourage patient to do ‘dummy’ injection
• Assess which delivery device patient prefers taking dexterity/vision into account
• Advise patient to record FBG in monitoring book until insulin start appointment
• Give prescription for needles, sharps bin, pen device + insulin. Lancets and BG

strips if required

• Advise re storage of insulin, and what to bring for Insulin Start appointment

(needles, insulin + pen device, BG record book + meter)

Insulin Start and Review

• Session one (insulin start)
• How to use the device safely +

correctly

• When to inject
• Where to inject + site rotation
• Sharps disposal
• Storage of insulin
• How to self-titrate insulin
• Hypoglycaemia – causes, signs +

treatment

• Diabetes + driving
• ID card + insulin passport
• Session two (insulin review)
• Insulin administration
• Hypoglycaemia – causes, signs, tx
• Self-titration of insulin dose
• Sick day rules
• Travel with insulin
• Insulin treatment, weight & exercise
• Annual review checklist – BP, HbA1c,

cholesterol, ACR, kidney function, eyes, feet, weight, lifestyle + well-being

Follow up…

• Patient continues to self-titrate insulin to target blood

sugar

• Waking glucose 5.5-7.5
• Pre-lunch and dinner 4.5-7.5
• Pre-bedtime 6.5-8.5
• Review in Tier 2 for ongoing support as needed
• GP/PN to recheck Hba1c in 3/12. If Hba1c still sub-
• ptimal, review in Tier 2 with CDSN

The right insulin

• Begin with human NPH (isophane) insulin:-
• Humulin I
• Insulatard
• Insuman basal

(Nice Diabetes Guidelines 2015)

• Start a once nocte basal insulin + OHA’s
• Aim to normalise fasting blood glucose levels (5.5-7.5) so

OHA’s work more effectively during the day

• Start 10 units of insulin – usually before bed but between

0.2-0.4 units/ kg may be needed

Initial Dose

When to Change the Dose of Once Daily Insulin

• Every 3 days, review the fasting blood glucose readings
• If over the past 3 days the fasting blood glucose level is >6mmols/l,

increase insulin by 2 units

• Stop increasing insulin when the fasting blood glucose level is 5.5 –

7.5mmols/l and stay on the dose you have reached

Insulin Types

• Human insulins - (laboratory made synthetic insulin)
• Analogue insulins - (sub-group of human insulin, genetically modified)
• Animal insulins - (pork, beef)

What insulins do you know?

Short Rapid Intermediate Mixtures Long Very Long

Short

Humulin S Actrapid

Rapid

Novorapid Humalog Apidra

Intermediate (NPH)

Humulin I Insulatard Insuman Basal

Mixtures

Humulin M3 Novomix 30 Humalog Mix 25 Humalog Mix 50

Long

Glargine (Lantus) Detemir (Levemir)

Ultra long-acting insulin

Tresiba/ Degludec

New insulins

Insulin Comments Launch Cost

Fiasp (Novo) Type I / II Works twice as quickly as Novorapid Closely matches physiological insulin response Pronounced improvement with pumps January 17 5x3ml pens £28.31 Same as Novorapid Toujeo (Sanofi) Ultra Insulin Glargine 300 units / ml 18-26 hrs duration Developed for those with large daily requirements Similar efficacy to glargine and same safety profile Not dose equivalent August 15 3 x 1.5ml pens £33.13 Same as Lantus Degludec (Novo) Ultra Insulin – 100 units / ml and 200 units / ml 42 hours action Increased flexibility in dosing Non inferior to Glargine Decreased rate of night hypos Medication errors with 200 units / ml March 13 100 units 5x3ml pens £72 200 units 3x3ml pens £86.40 Abasaglar (Lilly) Type I/II Biosimilar to Lantus - created from same protein sequence as Lantus Long acting glargine September 15 5x3ml pens £35.28

New Insulin Combinations

Insulin Combo Comments Launch Cost

Xultophy (Novo) Degludec and Liraglutide Reduction in HBA1c of 1.8% (Lantus 1.1%) Weight loss of 3lbs comparied to weight gain with Lantus alone Less hypoglycaemia than patients taking higher doses of Lantus For those with inadequate blood glucose control June 15 100 units/3.6mg per ml, 3 x 3ml pre- filled pen=£95.53 Lixilan (Sanofi) Lxyumia and Lantus IN development

Insulin Regimens for T2DM

• Once daily basal – usual starting point
• For patients who are insulin resistant, and have high fasting blood glucose
• Used with OHA’s, including Metformin, Gliclazide, DPP-4 (Gliptins), Pioglitazone
• Twice daily mixed insulin
• For patients where OHA’S are no longer stimulating efficient insulin production, leading to high

blood glucose post meal

• Suitable for those with a regular meal pattern
• Four times daily – (basal bolus)
• greater flexibility, may enable better control
• OD basal insulin, and bolus (quick acting) insulin with meals

Insulin regimens and examples

Regimen

• Basal OD (isophane) + OHA’s
• Basal OD (analogue) + OHA’s
• Human BD Mixtures
• Analogue BD Mixtures
• Basal + (plus)
• Basal bolus (+++)

Example

• Humulin I, Insulatard, Insuman Basal
• Glargine, Detemir
• Humulin M3
• Novomix 30, Humalog Mix 25, Humalog Mix 50
• Glargine or Detemir and rapid acting analogue

with main meal

• Glargine or Detemir and rapid acting with each

meal

Insulin dose adjustment

Principles of dose adjustment

• Individual targets should be agreed with patient; ask patient what they think of

their results?

• Waking 5.5-7.5mmol/l
• Pre-lunch and dinner 4.5-7.5mmol/l
• Pre-bed 6.5-8.5mmol/l
• Adjustment of insulin dose must be on the basis of a trend and not one

reading (look for a 3-7 day pattern)

• Ideally change one dose at a time to avoid confusion, and time for results to

become apparent

Principles of dose adjustment

• Adjust for low BGL’s first (never treat high BGL’s if hypos are present or

suspected). Consider night-time hypos with rebound waking hyperglycaemia

• Insulin dose change alone will not necessarily achieve good control
• Ensure dietary intake is considered
• Consider effect of different daily activities e.g. gym on Mon, Wed, Fri;

Before changing insulin dose, always consider:-

• Anxiety/depression
• Adherence to insulin/OHAs
• Accurate use of meter
• Insulin – expiry, correct storage
• Injection technique: dexterity, vision,

injection sites, needle length, correct dose

• Inactivity
• Timing of injection/tablets in relation to

food

• Illness + infection
• Diet ++ / alcohol ++
• Other medications eg steroids
• Stress
• Weight gain
• Heat

Changing insulin regimens

• If patient is not controlled on current regimen and potential issues affecting

glycaemic control have been considered:

• refer patient to Tier 2 clinic for assessment of treatment options.

Case Studies

James (44 yrs) - On max OHA’s and recently commenced daily Humulin I before bed What insulin dose should he be on? What lifestyle advice?

Date May

Insulin dose Blood glucose results Notes

B L D B BB AB BL AL BD AD BB 1 10 2 10

11.2

3 10

10.1

4 10

9.4 16.3 Large curry

5 10

13.2

6 10

9.1 17.4 Ate late

7 10

14.3

• Increase bedtime insulin to 12 units
• Reduce evening portion size
• Avoid late night eating
• Possible referral to dietitian

James (44 yrs) - On max OHA’s and recently commenced daily Humulin I before bed What insulin dose should he be on? What lifestyle advice?

George (60yrs) Insulatard insulin BD :- 26Units with breakfast and 24Units with evening meal What dose adjustment?

Date May

Insulin dose Blood glucose results Notes

B L D B BB AB BL AL BD AD BB 1 26 24

3.4 12.6 11.2 12.6

2

3.8 15.4 16.5 15.2

3

2.1 12.8 15.3 14.7

4

2.7 15.1 17.8 23.7

5 6 7

• Reduce evening insulin by 20%
• Review blood glucose readings every 3 days
• Aim for fasting blood glucose levels between 5.5 –

7.5mmols/l – then review daytime readings

• Discuss hypoglycaemia treatment
• May need to increase morning insulin to achieve pre-meal

targets of 4.5-6.5mmols/l and bedtime 6.5-8.5mmols/l

George (60yrs) Insulatard insulin BD :- 26Units with breakfast and 24Units with evening meal What dose adjustment?

Jennifer (58 yrs) - Novomix 30 insulin BD, BMI 28, no regular physical activity What insulin adjustment? What lifestyle advice?

Date May

Insulin dose Blood glucose results Notes

B L D B BB AB BL AL BD AD BB

1 42 22 12.3 9.1 2 42 22 12.1 10.3 3 42 22 8.3 4 42 22 9.2 8.6 16.8

Large Chinese meal

5 42 22 5.9 10.1

Walk before lunch

6 42 22 11.9 7 42 22

• Increase evening insulin dose by 10% to improve fasting

blood glucose levels (5.5-7.5mmols/l)

• Encourage activity post meal
• Reduce portion sizes and not eat too late
• Possible referral to dietitian

Jennifer (58 yrs) - Novomix 30 insulin BD, BMI 28, no regular physical activity What insulin adjustment? What lifestyle advice?

Paul (66yrs) Humalog Mix 25 insulin:- 60Unit with breakfast, 34Unit with evening meal What dose adjustment?

Date JAN

Insulin dose Blood glucose results Notes

B L D B BB AB BL AL BD AD BB

1 60 34 6.5 3.8 11.9 8.7 2 9.0 3.3 17.8 6.8 3 5.5 4.0 9.0 5.4 4 4.9 2.9 25.9 5.5 5 6 7

• Reduce breakfast insulin by 10 -20%
• Review readings every 3 days and titrate to 4.5-7.5mmol/l
• Review activity levels during the day
• Once hypoglycaemia is resolved – review before dinner and

bedtime readings

Paul (66yrs) Humalog Mix 25 insulin:- 60Unit with breakfast, 34Unit with evening meal What dose adjustment?

Beatrice (74 yrs) - Humulin M3 insulin BD, erratic eater, lives alone, walks with a stick. What insulin adjustment? What other advice?

Date JAN

Insulin dose Blood glucose results Notes

B L D B BB AB BL AL BD AD BB

1 52 22 3.2 2 52 22 4.1

Dizzy after lunch

3 52 22 4 52 22 6.2

Dizzy before dinner

5 52 22 6 52 22 2.3 4.3 7 52 22

• Both insulin doses need reducing to avoid hypos 10-20%
• Educate re hypoglycaemia Sx & Mx
• Consider switching to Humalog Mix 25 or Novomix 30 OR
• Consider stepping down to a basal insulin + oral

hypoglycaemia treatment options

• Review previous medication history
• Encourage more frequent monitoring and follow up
• Encourage regular meals patterns

Beatrice (74 yrs) - Humulin M3 insulin BD, erratic eater, lives alone, walks with a stick. What insulin adjustment? What other advice?

Jim (49 yrs) Basal bolus insulin regimen (Glargine OD, and Novorapid TDS), and max Metformin. Main meal at lunchtime. What insulin adjustments?

Date May

Insulin dose Blood glucose results Notes

B L D B BB AB BL AL BD AD BB

1 6 6 6 12 10.4 6.3 2 6 6 6 12 8.2 15.1 10.2 3 6 6 6 12 9.7 5.9 9.8 4 6 6 6 12 9.2 14.9 7.0 5 6 6 6 12 8.6 6.1 11.1 6 6 6 6 12 7.5 7 6 6 6 12 8.0

• Increase evening basal insulin by 10 – 20% aiming for

waking glucose 5.5-7.5mmol/l

• Increase lunchtime novorapid aiming for pre-dinner

glucose 4.5-7.5mmol/l

• Refer to dietitian to discuss carbohydrate counting

Jim (49 yrs) Basal bolus insulin regimen (Glargine OD, and Novorapid TDS), and max Metformin. Main meal at lunchtime. What insulin adjustments?

Sarah (40 yrs) On max OHA’s started Insulatard 4 months ago. She titrated her insulin to 32Unit daily but Hba1c = 70mmol/mol after stabilisation. What could be next course of action?

Date May

Insulin dose Blood glucose results Notes

B L D B BB AB BL AL BD AD BB

1 32 4.6 5.8 12.3 2 32 5.4 8.7 12.0 3 32 5.3 6.3 11.8 4 32 11.9 5 32 5.2 13.7 6 32 4.7 7 32 * 10.0 *lunch

• ut

• Consider changing Insulatard to LAIA (eg Levemir at

same dose)

• Discuss portion sizes +/- dietitian referral
• Consider post-prandial hyperglycaemia
• Consider basal plus (i.e rapid insulin with dinner) as next

step

Sarah (40 yrs) On max OHA’s started Insulatard 4 months ago. She titrated her insulin to 32Unit daily but Hba1c = 70mmol/mol after stabilisation. What could be next course of action?

Conclusions

• Diabetes pathophysiology and burden of disease
• Identify those who may benefit from insulin therapy
• Referral to your community service or acute trust
• CLCHT.wandsworthspa.nhs.uk or SGH as indicated
• Kinesis – Dr Roni Saha
• Insulin types and regimens
• How to titrate insulin to individualised Hba1c and CBG targets

Questions???