Type 2 diabetes is a major public health issue costing the NHS billions each year. It is caused by a combination of genetic and environmental factors and results in insufficient insulin production and ineffective use of insulin by the body. Treatment involves lifestyle changes like diet and exercise as well as drug therapies targeting blood glucose, blood pressure, and cholesterol levels. Recent evidence shows that intensive lifestyle interventions can help achieve remission of type 2 diabetes in some patients through significant weight loss.

1. Type 2 Diabetes Mellitus
Ching Yee Ngan
Practice Support Pharmacist
City and Hackney CCG
ching-yee.ngan@nhs.net

2. Learning objectives
• Type 2 diabetes recap and complications
• Management of type 2 diabetes
 Non-pharmacological, including diet
 Drug treatment
• CVOTs and other recent evidence
• Hypoglycaemia
• Self-monitoring of blood glucose
• Guidelines – local and national
• Medication review

3. The cost of diabetes
Major public health issue:
3.9 million in the UK have with diagnosed diabetes (2019 figure)
Almost 1 million people with type 2 diabetes in the UK are yet to be diagnosed
1 in 15 people have diabetes in the UK
Prevalence increasing in UK - to ~5 million by 2025
£££ NHS £14 billion/yr including complications (10% of NHS budget)
Why? Ageing population, rapidly rising numbers of overweight & obese, ethnic group structure of
population
Risk depends on combination of genetics, lifestyle & environmental factors

4. Types of diabetes mellitus
• Type 1 diabetes (8%)
• Type 2 diabetes (90%)
• Gestational diabetes – 16% pregnant women in the UK
• Some of other types of diabetes
• Latent Autoimmune Diabetes in Adults (LADA)
• Maturity Onset Diabetes of the Young (MODY)
• Steroid- induced diabetes (or drug-induced)
• Type 3c diabetes – secondary to pancreatic diseases such as CF, pancreatitis,
pancreatic cancer, haemochromatosis

5. Type 2 Diabetes Mellitus
• Multifactorial (genetic & environmental)
• Strong family link (2-6 x increased risk)
• Progressive deterioration of islet β-cell function
• Defective insulin production
• Inability to use insulin effectively (insulin resistance)
• Insufficient insulin to maintain normal blood glucose but enough to
sustain body mass and inhibit fat and muscle breakdown
• Commonly associated with metabolic syndrome
• Develops with ↑ age, obesity and physical inactivity
• Reduced life expectancy ~ 10yrs for T2DM

7. Risk factors of type 2 diabetes
• Age (>40y or >25y for South Asian,
exception- obese adolescents)
• Ethnicity (South Asian x 6, Black
African & Afro Caribbean x 3, Chinese
– even if UK born)
• Develops earlier in SA, BA & BAC
• Family history
• Diet - processed foods, little fibre,
poor quality fats
• Obesity
• Lack of exercise
• Stress
• Hypertension
• CHD
• Polycystic ovarian syndrome
• Severe mental health problems
(e.g. schizophrenia, depression
under drug therapy)
• Hx of gestational diabetes or
impaired glucose tolerance

8. Diagnosis
WHO (Jan 2011) recommend HbA1c for diagnosis
• HbA1c 48mmol/mol (6.5%) recommended as cut off
• <48mmol/mol - doesn’t exclude diabetes diagnosed using glucose tests
• In those without symptoms of diabetes – HbA1c should be repeated – if second sample is <48mmol/mol then
person should be treated as high risk of diabetes and test should be repeated in 6 months or sooner if
symptoms develop.
• Finger-prick HbA1c must be confirmed by laboratory venous HbA1c in all patients
WHO 2011 recommendations:
High diabetes risk HbA1c 42-47 mmol/mol (6.0 – 6.4%)
Provide intensive lifestyle advice
Warn patients to report symptoms of diabetes
Monitor HbA1c annually
HbA1c under 42 mmol/mol (6.0%)
May still have high diabetes risk
Review personal risk and treat as “high diabetes risk” as clinically indicated

9. Presentation
• Osmotic symptoms (polydipsia, polyuria, nocturia)
• Blurred vision
• Infections - vaginal candidiasis, recurrent UTI’s
• Lethargy
• Weight loss
• Macrovascular complications
• Microvascular complications

10. Microvascular complications
Diabetic Eye
Blurred vision, rapid changes in BG control
Open-angle glaucoma
Cataracts
Retinopathy
Peripheral Neuropathy
More common in elderly T2DM
Progressive loss of peripheral nerve fibre
3 main types: sensory, autonomic, and motor
Distal sensory neuropathy- mainly affects feet
Autonomic neuropathy…ED, dry skin, lack of sweating

11. Microvascular complications
Diabetic Nephropathy
 Microalbuminuria
 Nephrotic syndrome
 Chronic kidney disease
 End stage renal failure
 Dialysis
Diabetic foot
 Neuropathic ulceration
 Ischaemic ulcers
 Infected foot ulcers
 Foot care
 Education- avoid amputation

13. NHS Diabetes Prevention Programme
• The NHS Diabetes Prevention Programme (NHS DPP) supports those at high risk
of Type 2 diabetes to reduce their risk, via a 9 month supported lifestyle
intervention to achieve a healthy weight, improve nutrition and increase
physical activity.
• Who is eligible?
• ≥18 years with nondiabetic hyperglycaemia, which is defined as having an
HbA1c of 42 to 47 mmol/l or 6.0 to 6.4% or fasting plasma glucose of 5.5 to
6.9 mmol/l. These individuals are at high risk for progression to Type 2
diabetes.

14. Management of type 2 diabetes
mellitus

15. CV risk management
NICE BP management in diabetes
• Updated guidance August 2019
• 1st line ACEI or ARB
• ARB preferred for black African or African-Caribbean family origin
• BP target <140/90 but <130/80 if patients also have CKD

16. CV risk management
NICE guidance regarding statins in T2 DM:
• Offer atorvastatin 20mg for primary prevention to T2 patients who have a
10% or greater 10-year risk of developing CVD (QRISK)
NICE guidance regarding antiplatelet therapy:
• Do not offer antiplatelet therapy (aspirin or clopidogrel) for T2 adults
without CVD

17. Non-pharmacological management
Healthy living advice
• Daily physical activity e.g. walking, swimming
• Smoking cessation
• Weight reduction - improve glycaemic control
Dietary
• BG closely affected by carbohydrate intake - carb consumption appropriate to physical activity, portion size important
• Total exclusion of sugar unnecessary
• ‘Diabetic foods’ – discourage
• ↑fibre (Dietary fibre minimises hyperglycaemia)
• ↓sugar, salt (reduces BP) and fat
• Eat 5 portions of fruit & veg a day
• Alcohol in moderation
Structured Education
• DESMOND (for T2 only)
• X-PERT (for both T1 and T2)

18. • Diabetes Remission Clinical Trial (DIRECT) – To assess if a low calorie diet, alongside wt
management support, within routine primary care, would achieve remission of T2DM
• Open-label, cluster-randomised trial at 49 GP practices in Scotland and Tyneside
• Wt management programme (intervention) vs best-practice care by guidelines (control)
• People aged 20-65 with T2DM within past 6 yrs and BMI 27-45 kg/m², not receiving
insulin
• 149 participants per group
• Antidiabetic and antihypertensive drugs withdrawn in intervention group
• Total diet replacement (825–853 kcal/day formula diet for 3–5 months), stepped food
reintroduction (2–8 weeks), and structured support for long-term wt loss maintenance

19. • Co-primary outcomes:
• Weight loss at least 15kg at 24 months
• Remission of diabetes (HbA1c <48mmol/mol (6.5%) after withdrawal of anti-diabetes medications at baseline)
• Diabetes remission achieved in 46% intervention group and 4% in control group at the end
of 12 months
• 2-year results available in early 2019
• The programme sustained remissions at 24 months for more than a third of people with T2DM
• Sustained remission was linked to extent of sustained wt loss
Intervention Control
Wt loss at least 15kg 17 pts (11%) 3 pts (2%)
Diabetes remission 53 pts (36%) 5 pts (3%)

20. Low Energy Diet in Hackney

21. Total Diet
Replacement (TDR)
12 weeks
Food
Reintroduction (FR)
2 months
Weight
Maintenance (WM)
7 months
Group 1
Group 2
Group 3
Group 4

24. Low Carb Programme
• A digitally delivered self management education programme for T2 diabetes,
prediabetes and obesity
• Structured learning, goal focussed with community support
• Tailored meal plans, mobile App
• A low carb diet is < 130g of carb/day
• Aim to avoid or have minimum ‘white stuff’ such as bread, pasta and rice, also sugar,
snacks, alcohol
• Encouraged to have leafy green veggies, protein and healthy fats
• Less tropical fruits, berries are better, apples and pears are fine in moderation
• Positive outcomes after 1 year – reduction in HbA1c and weight loss, less medication

25. Common foods and sugar
https://phcuk.org/sugar/

26. Sugar burden
https://phcuk.org/sugar/

27. Drug treatment
Pills, pills and more pills

28. Oral hypoglycaemic drugs – where do they work?

29. Biguanides - metformin
• Works by altering several metabolic pathways
Inhibits hepatic gluconeogenesis
Increases peripheral glucose utilisation by enhancing insulin action at receptors
Increases glucose uptake by muscles
Favourable effect on lipid metabolism- decreases fatty acid oxidation
• Dose: titrate, take with/after food
• Adverse effects: anorexia, nausea, abdominal discomfort, diarrhoea, lactic acidosis, metallic taste, decreased
Vitamin B12 absorption
• Cautions/contra: renal/hepatic disease, hx of acidosis, use of IV radiographic contrast media
• Benefits include: no hypo, can be combined with other oral hypoglycaemics and insulin, reduces risk of MI
(UKPDS), cheap, doesn’t cause weight gain and may promote weight loss
• MR prep ↓ GI S/E, reserved for patients who don’t tolerate GI S/E of standard release; max dose 2g/day
• Review dose if eGFR <45ml/min/1.73m² and stop if <30ml/min/1.73m²
• Can be considered in T1 adults if BMI ≥25 kg/m², also in gestational diabetes (NICE)

30. Sulfonylureas
• Work by direct stimulation of functionally capable β-cells causing release of insulin
• Must have residual pancreatic β cell activity
• No evidence of macrovascular risk reduction in trials
• Take with food
• Short/intermediate acting – gliclazide, glipizide, glimepiride, tolbutamide
• Long acting – glibenclamide – now discontinued
• Caution: hepatic impairment
• Adverse effects (low frequency):
Hypoglycaemia
Gastrointestinal disturbances
Weight gain
Deranged LFTs

31. Meglitinide analogues
• Repaglinide or Nateglinide
• Prandial glucose regulators (PGRs) - stimulate insulin release relative to glucose levels
Stimulating insulin release
Close K+-ATP channels on surface of pancreatic cells
Enabling postprandial glycaemic response
• Need residual pancreatic function
• Rapid onset (30 mins) - but short lived stimulation of insulin secretion (secretagogues); hence control post prandial glucose
levels
• Within 30 minutes before food - avoid dose if miss meal - frequency depends on how many main meals/per day
Benefit: use in individuals with erratic lifestyles - should not be used with SU but can be used instead of SU; short-acting and
safer than SU in renal impairment
Adverse effects: mainly hypoglycaemia
Caution: hepatic or severe renal impairment

32. DPP-4 inhibitors (Gliptins)
• Dipeptidyl peptidase 4 (DPP-4) inhibitors
• Work by
Competitively inhibit DPP-4 increasing active incretins (GLP-1 and GIP)
Suppress glucagon secretion
Stimulate glucose dependant insulin secretion
Slow gastric emptying
Increase tissue sensitivity to insulin
•Incretin hormones have a short half life and are broken down by DPP-4
•Increase availability of incretins (GLP-1) hormones produced by the GI tract

33. DPP-4 inhibitors (Gliptins)
• Formulary – sitagliptin and linagliptin
• Non-formulary - vildagliptin, saxagliptin and alogliptin
• Unaffected by food - take any time
• Adverse effects: increased risk for infection, headache, GI side effects, pancreatitis
• Benefits: Low rates of hypoglycaemia and weight neutral…useful if weight gain is a
problem
• Reduce dose in renal impairment except linagliptin
• Liver toxicity with vildagliptin
• In April 2016, FDA issued drug safety alert re increased risk of heart failure with
saxagliptin and alogliptin, particularly in patients who already have heart or kidney
disease. Consider discontinuing in patients who develop heart failure.

34. Thiazolidinediones- Pioglitazone
• Work by
Selectively stimulating nuclear receptor peroxisone proliferator-activated receptor gamma (PPAR-gamma)
Modulates the transcription of insulin-sensitive genes involved in the control of glucose and lipid metabolism in
the lipidic, muscular tissues, and liver
Increase glucose uptake into cells
Reduce insulin resistance
Decrease hepatic glucose production
• Improve insulin sensitivity by stimulating PPAR – mainly adipose tissue
• Adverse effects: GI, oedema, liver toxicity, weight gain, anaemia, headache, altered lipids,
bladder cancer, haematuria, fracture risk, increased risk of HF if used with insulin
• Cautions/contra: hepatic impairment, HF, bladder cancer, elderly
• Rosiglitazone withdrawn in 2010 due to increased risk of heart attack and stroke

35. Alpha glucosidase inhibitors
• Acarbose
• Works by
Preventing breakdown of carbohydrates in GI tract
Delays digestion and absorption of glucose
Reduces postprandial blood glucose
• Small effect in lowering blood glucose
• Not as effective as other agents
• Not mentioned in NICE NG28
• No incidence of hypos
• Adverse effects:
GI related e.g. flatulance

36. Glucagon-like peptide 1 receptor
agonists (GLP-1RA)
• Formulary - liraglutide (OD), lixisenatide (OD), dulaglutide (OW)
• Non-formulary - exenatide (Bydureon MR-OW and Byetta IR- BD), semaglutide (OW inj or OD oral)
• Mostly subcutaneous injections except oral semaglutide
• Similar to incretin hormone GLP-1, also called incretin mimetics
• Bind to and activate GLP-1 receptor
Increase endogenous insulin secretion
suppress glucagon secretion from pancreas
slow gastric emptying and reduce appetite
• Benefits: potential to promote weight loss, delay in starting insulin
• Combination preparation – liraglutide + insulin degludec (Xultophy); lixisenatide + insulin glargine (Suliqua)
• Liraglutide 3mg (Saxenda) for obesity

37. Glucagon-like peptide 1 receptor
agonists (GLP-1RA)
NICE recommends to use GLP-1RA:
If triple therapy not effective, not tolerated or contraindicated, consider combination with
metformin and SU for T2 patients whose:
BMI 35 or more and of European descent (adjust for other ethnic groups) and there are
problems with weight
BMI < 35 and insulin is unacceptable and weight loss is beneficial
• Continue if HbA1c reduced by at least 1% and weight loss of at least 3% at 6/12
• Adverse effects: GI side effects, low rates of hypoglycaemia – if occurs, consider dose
reduction of SU, pancreatitis
• Avoid exenatide and lixisenatide if eGFR <30; avoid dulaglutide, liraglutide and
semaglutide in end-stage renal disease
• MHRA drug alert in June 2019 – Reports of DKA when concomitant insulin rapidly
reduced or discontinued

38. Sodium-Glucose Co-Transporter 2
(SGLT-2) inhibitors
• Dapagliflozin, canagliflozin, empagliflozin & ertugliflozin (all have NICE TA)
• Reversibly inhibit sodium-glucose co-transporter 2 in the renal proximal
convoluted tubule
reduce glucose reabsorption
increase urinary glucose excretion

39. Sodium-Glucose Co-Transporter 2
(SGLT-2) inhibitors
• Insulin-independent renal elimination of glucose
• Can cause weight loss, lower BP
• Efficacy of glucose lowering effect is dependent on renal function
• Adverse effects: increased risk of genital infections due to glycosuria, UTI, volume
depletion, risk of DKA (including euglycaemic), hypo when used with SU or insulin
• Attractive option for T1 DM
• SGLT-2 and SGLT-1&2 inhibitors included in studies in T1 DM, increased risk of DKA a
concern
• Blocking SGLT-1 in the intestine delays and reduces glucose absorption into blood stream
• Sotagliflozin (SGLT-1&2 inhibitor) for T1 adults approved by NICE but not licensed in the
UK yet; dapagliflozin 5mg for T1 adults also has NICE TA

40. SGLT 2 inhibitors in renal
impairment
Dapagliflozin, empagliflozin and ertugliflozin:
Not to be initiated if eGFR <60ml/min/1.73m²
Discontinue if eGFR persistently <45ml/min/1.73m²
Canagliflozin:
Recently approved for use in diabetic kidney disease
eGFR (ml/min/1.73m²) or CrCl
(ml/min)
≥ 60 30 to < 60 < 30
Canagliflozin dose Initiate with 100mg od,
can be increased to
300mg od
Initiate with 100mg od,
continue 100mg od if
already taking
Do not initiate
Continue 100mg od if
already taking until dialysis
or renal transplantation

41. MHRA drug alerts for SGLT 2
inhibitors
• Risk of DKA (updated in April 2016)
• Monitor ketones in blood during treatment interruption for surgical
procedures or acute serious medical illness (March 2020)
• Amputation risk (updated in March 2017)
• Fournier’s gangrene (Feb 2019) - necrotising fasciitis of the genitalia
or perineum

42. Diabetes Cardiovascular Outcomes
Trials (CVOTs)
• U.S. Food and Drug Administration (FDA) in Dec 2008 issued guidance on
development of antidiabetes drugs for T2 DM
• Concerned about increased CVD risk with rosiglitazone at the time
• Subsequent similar requirements from European Medicines Agency
• Focussed on CV safety
• Major Adverse Cardiac Events (MACE) used as composite end point in CV studies
• 3 point-MACE – non-fatal stroke, non-fatal MI and CV death but definition can
vary
• 4-point-MACE – hospitalisation for unstable angina + 3-point MACE

43. DPP-4 inhibitors CVOTs
SAVOR-TIMI 53
(n=16492)
EXAMINE
(n=5380)
TECOS (n=14671) CARMELINA
(n=6979)
CAROLINA
(n=6033)
Intervention Saxagliptin vs placebo Alogliptin vs placebo Sitagliptin vs placebo Linagliptin vs placebo Linagliptin vs
glimepiride
Main inclusion criteria T2 & history of or
multiple risk factors
for CVD
T2 & ACS within 15 to
90 days before
randomisation
T2 & pre-existing CVD T2 & high CV risk T2 & increased CV risk
or established CVD
Year started /
reported
2010 / 2013 2009 / 2013 2008 / 2015 2013 / 2017 2010/2018
Primary end point 3-point MACE 3-point MACE 4-point MACE 3-point MACE 3-point MACE
Outcomes Ischaemic events not
↑ but ↑ HF
hospitalisation
CV events not ↑ but
non-significant trend
with HF
CV events and HF not
↑
CV events and HF not
↑
Non-inferior risk of
composite CV
outcome

44. GLP-1 RA CVOTs
ELIXA
(n=6068)
LEADER
(n=9340)
SUSTAIN-6 (n=3297) EXSCEL
(n=14752)
REWIND
(n=9901)
PIONEER 6
(n=3183)
Intervention Lixisenatide vs
placebo
Liraglutide vs
placebo
Semaglutide OW vs
placebo
Exenatide OW vs
placebo
Dulaglutide vs
placebo
Oral semaglutide vs
placebo
Main inclusion
criteria
T2 & ACS
within 180
days before
screening
T2 & pre-existing
CVD, CKD or HF at
≥ 50yrs or ≥ 1 CV
risk factor at ≥
60yrs
T2 & pre-existing CVD,
CKD or HF at ≥ 50yrs or ≥
1 CV risk factor at ≥ 60yrs
T2 with or without
pre-existing CVD
T2 with previous CV
events or risk
factors
T2 with established
CVD or CKD at ≥
50yrs or ≥ 60yrs
with CV risk factors
Year started /
reported
2010 / 2015 2010 / 2016 2013 / 2016 2010 / 2017 2011 / 2018 2017/2019
Primary end point 4-point MACE 3-point MACE 3-point MACE 3-point MACE 3-point MACE 3-point MACE
Outcomes Non-inferior
but no
beneficial CV
outcome
Non-inferior
CV death sig ↓
All cause mortality
sig ↓
Non-inferior
Favourable effect on
MACE; nonfatal stroke sig
↓; nonfatal MI nonsig ↓;
no trend for CV death or
all-cause mortality
Non-inferior
Treatment
persistence rate low
with 43% drug
discontinuation
CV events sig ↓ Non-inferior
Favourable effect
on MACE – fewer
CV deaths and
nonfatal stroke but
more nonfatal MI

45. SGLT2 inhibitors CVOTs
EMPA-REG
OUTCOME (n=7020)
CANVAS Programme
(CANVAS + CANVAS
R) (n=10142)
DECLARE-TIMI 58
(n=17160)
VERTIS-CV
(n=8246)
Intervention Empagliflozin vs placebo Canagliflozin vs placebo Dapagliflozin vs placebo Ertugliflozin vs placebo
Main inclusion criteria T2 & pre-existing CVD with
BMI ≤ 45kg/m² & eGFR ≥
30ml/min/1.73m²
T2 & pre-existing CVD at ≥
30yrs or ≥ 2 CV risk factors
at ≥ 50yrs
T2 & high risk for CV events T2 & established CVD
Year started / reported 2010 / 2015 2009 / 2017 2013 / 2019 2013/2019
Primary end point 3-point MACE 3-point MACE 3-point MACE; composite
of CV death or HF
hospitalisation
3-point MACE
Outcomes MACE sig ↓
CV death sig↓ (38%)
All-cause mortality sig ↓
(32%)
HF hospitalisation sig
↓(35%)
MACE sig ↓
HF hospitalisation sig ↓
(33%)
All-cause mortality
difference not statistically
sig in the truncated
integrated data set
Non-inferior but sig lower
rate of CV death or HF
hospitalisation (27%)
Non-inferior but sig
reduction in HF
hospitalisation (30%)

46. Other evidence for SGLT2 inhibitors
Renal outcomes study:
• Canagliflozin - CREDENCE
• From CREDENCE and most of the CVOTs - SGLT2 inhibitors except ertugliflozin
substantially reduced risk of dialysis, transplantation, or death due to kidney
disease, also reduced ESRD and AKI
• Evidence of renal benefit even for patients with a baseline eGFR 30-
45ml/min/1.73m² although less effective at lowering blood glucose
• Awaiting results of other renal outcomes trials – EMPA-KIDNEY and DAPA-CKD

47. Other evidence for SGLT2 inhibitors
Published heart failure study :
• Dapagliflozin - DAPA-HF (2019)
• Patients with or without diabetes who had a reduced ejection fraction ≤ 40%
• Primary outcome – composite of worsening HF or CV death
• Significant reduction in primary outcome, both with or without diabetes
• Licence change expected to include treatment of HFrEF soon
Other HF studies to be completed:
• Dapagliflozin – DELIVER (expected 2021) – for patients with HFpEF
• Emapagliflozin – EMPEROR-reduced and EMPEROR-preserved (both expected end of
2020)

48. Treatment with insulin

49. Insulin therapy in type 2 diabetes
mellitus
• Many type 2 patients will require insulin as pancreatic beta cell function declines over time
• Can cause hypo and weight gain
• Treatment option should reflect:
Lifestyle, general well being, ability to self-test BGs
Choice of device
Who will administer
• NICE recommends
• Continue to offer metformin if no contraindications or intolerance
• Review the continued need for other hypoglycaemic drugs
• Common regimens
• A single daily (usually ON) dose of basal insulin with metformin and other oral hypoglycaemics
• BD (before breakfast and evening meal) pre-mixed combinations or basal bolus with metformin
• Target blood glucose levels: May vary, could be 4 to 7mmol/L before meals and < 8.5mmol/L 90mins post meals
• Human NPH insulin - preferred basal insulin as per NICE
• LA insulin analogues (detemir, glargine) recommended by NICE in specific patient circumstances

50. Types of Insulins

51. Types of Insulins
Soluble ( Human) Actrapid, Humulin S, Insuman Rapid
Rapid acting (analogue) Humalog, Insulin lispro Sanofi, Lyumjev, Novorapid, Fiasp, Apidra
Intermediate acting (NPH) Humulin I, Insulatard, Insuman Basal
Long acting (analogue) Levemir, Tresiba, Lantus, Abasaglar, Semglee, Toujeo
Pre-mixed/biphasic (Human) Humulin M3, Insuman Comb 25, Insuman Comb 50
Pre-mixed/biphasic (analogue) Novomix 30, Humalog Mix25, Humalog Mix50
• Mainly 100units/ml but also 200units/ml (Humalog, Lyumjev, Tresiba), 300units/ml (Toujeo),
even 500units/ml (unlicensed Humulin R)
• Biosimilars available for insulin glargine (Abasaglar, Semglee) and insulin lispro (insulin lispro
Sanofi) - cheaper

52. Timing of insulins
Insulin Usual frequency Timing
Short or rapid acting Three times a day, depending on number
of meals a day
Humulin S – 20 to 45mins before meals
Insuman Rapid – 15 to 20mins before meals
Novorapid. Humalog, Apidra – 10 to 15mins before or just before or
with or just after meals
Fiasp & Lyumjev – Up to 2mins before or with or up to 20mins after
meals
Patients need to eat after injections
Intermediate acting Once or twice a day Humulin I – 30mins before food or bedtime
Insuman Basal – 45 to 60mins before food
If given once a day, mostly given at night but sometimes morning
Long acting Once a day (Levemir sometimes given
twice a day)
Any time but the same time each day
If given once a day, mostly given at night but sometimes morning
Pre-mixed/biphasic Mostly twice a day , some patients might
need three times a day
Humulin M3 – 20 to 45mins before meals
Insuman Comb – 30mins before meals
Novomix 30, Humalog Mix - 10 to 15mins before or just before or
with or just after meals
Patients need to eat after injections

53. Injection technique
• Insulin absorption is fastest in the
abdomen, slow in the thighs and slowest
in the buttocks
• Cloudy insulin needs mixing before each
injection
• Keep insulin pen in use at room temp
and new ones in fridge
• 2 units test dose
• Inject at 90° angle, push down to give full
dose and then count at least 10secs
• Not necessary to lift skin fold unless
patient very slim
• Always rotate injection sites to avoid
lipohypertrophy
• New needle for each dose, sharps bin
• Pen needle length should be 4mm or
5mm to avoid IM injection
Lipohypertrophy

54. Example of initiating and adjusting basal insulin
in type 2 diabetes
TREND UK
https://trend-uk.org/wp-content/uploads/2019/12/HCP_Basal_TREND_DEC19_v3.pdf

55. Case study – Adjusting insulin doses
Sam is a 58 year old type 2 diabetic and is on Humulin M3 kwikpen 14units om and
14units evening, and metformin 1g bd. His recent HbA1c is 64mmol/mol (8%)
which has worsened since last year. He monitors his blood glucose once or twice a
day and the readings are usually between 7 to 10mmol/L before breakfast and
between 8 to 11mmol/L before evening meal. His renal function is normal.
1. What target blood glucose level is appropriate for Sam?
2. What frequency of blood glucose monitoring is appropriate?
3. What could be contributing to his high blood glucose levels?
4. What advice would you give to Sam and how would you adjust his insulin
doses?

56. Case study – Adjusting insulin doses
1. What target blood glucose level is appropriate for Sam?
Could be 4 to 7mmol/L before meals and < 8.5mmol/L 90mins post meals
2. What frequency of blood glucose monitoring is appropriate?
2 to 4 times a week if stable, more frequent if unstable or unwell
3. What could be contributing to his high blood glucose levels?
? Adherence problem
? Incorrect injection technique resulting in lipohypertrophy
? Timing of Humulin M3, avoid mismatch between insulin and food
? Change of diet
? Any new med

57. Case study – Adjusting insulin doses
4. What advice would you give to Sam and how would you adjust his insulin doses?
• Discuss timing, diet, injection technique, etc
• To adjust Sam’s insulin:
 Dose which needs to be changed is the one preceding the reading that
needs to be improved
 The usual method for adjusting doses is to alter the dose by 2 units or 10%
 The trend should then be monitored for 3 to 4 days before making any
further amendments
• Always look at the trend and any reasons

58. Hypoglycaemia BG <4.0mmol/L
• CAUSES
• Mismatch of food & insulin time – too much insulin
• Strict blood glucose control
• Incorrect dose of oral hypoglycaemic
• Delayed/missed meal/snack
• Insufficient carbs
• Unawareness of hypoglycaemia
• Strenuous activity - eat carbs before, and during if long activity. Can happen up to 36hrs after. Adjust
meds/carb intake
• Alcohol/drinking without food –signs of hypos are similar to being drunk
• Sometimes – no obvious cause
• SYMPTOMS
• Sweating, pounding heart, tremor, hunger, nausea, headache, confusion, drowsiness, speech difficulty, lack of
co-ordination, atypical behaviour, diplopia,
• Night time hypos: patients might not be aware, may wake up feeling tired, with a headache or have a
hangover sensation. Most likely to occur 2-3am; could check levels if concerned have night time snack

59. Treatment of hypoglycaemia in
community
Guidance from HUH Diabetes Centre
(from C&H GP website diabetes download):
• Use fast acting carbohydrate
• Check BG 15 to 20mins afterwards
• If BG still <4, repeat hypo treatment
• When BG within range, have some slow
release carbohydrate such as bread,
biscuits, fruit, etc

60. Sick Day Rules for type 2 diabetes
TREND UK guidance
for type 2 patients
https://trend-uk.org/wp-content/uploads/2020/03/A5_T2Illness_TREND_FINAL.pdf

61. NICE - Self-monitoring of blood
glucose
• Take the DVLA guide to the current medical standards of fitness to drive into account when
offering self monitoring of blood glucose levels for adults with T2DM
• Do not routinely offer self-monitoring of blood glucose levels for adults with T2DM unless:
 the person is on insulin OR
 there is evidence of hypoglycaemic episodes OR
 the person is on oral medication that may increase their risk of hypoglycaemia while driving
or operating machinery OR
 the person is pregnant, or is planning to become pregnant
 Consider short-term self-monitoring when starting treatment with oral or IV corticosteroids
or to confirm suspected hypo

62. Blood glucose meters
• Finger-prick test
• Lancing device needed for lancets
• Testing strips used
• Could be difficult for some patients to use

63. FreeStyle Libre
• Sensor – 2/month
• Reader
• Flash glucose monitoring system
• Glucose level in interstitial fluid
• Wear sensor for up to 14 days
• Scan sensor on reader
• Reader displays the current glucose
reading, the latest 8hrs of continuous
glucose data and a trend arrow
• LibreLink app on Android smartphone
• LibreLink app syns automatically to
LibreView to connect with HCP, family,
etc
• FreeStyle Libre 2 with alarm not
available in the UK yet

64. FreeStyle Libre – prescribing criteria
• NHSE national arrangements for funding Flash Glucose Monitoring from April 2019
• NHSE to reimburse CCGs for ongoing costs of flash glucose sensors for patients who
meet the criteria and may represent up to 20% of T1DM population
• Criteria:
 People with T1 or with any form of diabetes on HD + insulins, who need BG monitoring
>8x/day; or diabetes associated with CF on insulins
 T1 pregnant women
 T1 unable to routinely self-monitor due to disability
 T1 with occupational or psychosocial circumstances that warrant a 6-month trial
 Previous self-funders who would have satisfied one or more of these criteria
 T1 with recurrent severe hypo or impaired awareness should use CGM but Flash Glucose
Monitoring system might be more appropriate in some people

65. C&H guideline for blood glucose meters, testing
strips and lancets in uncomplicated type 2 diabetes
• Choice of BG testing strips:
 TEE2 (for TEE2+ meter)
 Contour (for Contour (black) meter)
 Performa (forAccu-Chek Performa Nano meter)
 Mobile test cassette (for Accu-Chek Mobile meter)
• Info on frequency of self-monitoring of BG
• Requirements of self-monitoring of BG for drivers
• The guideline does not apply to type 1 or pregnant patients

66. Frequency of self-monitoring from C&H guideline

67. Requirements for drivers – from C&H guideline

68. C&H guideline for pen needles for insulin
and GLP-1 analogue pens
• Recommended pen needles:
 GlucoRx CarePoint
 BD Viva
 4SURE
 Tricare
• Also info on:
 Pen needle length
 Safe disposal
 Safety needles – mainly for HCPs but some can be used for patients who are
needle phobic

69. Treatment guidelines

70. Algorithm for blood glucose lowering therapy in T2 diabetes
(NICE NG 28)

71. NICE Patient Decision Aid
• Available to help T2 patients make informed decision about first intensification

72. SIGN 154
• Scottish guideline 2017
• Key recommendations for T2 DM:
 A target HbA1c of 7% (53mmol/mol) in T2 reasonable (6.5% at
diagnosis) but should be individualised to balance benefits with
harms
 Metformin as 1st line for T2
 SGLT2 inhibitors with proven CV benefits should be considered in
T2 with established CVD
 GLP-1 RAs with proven CV benefits should be considered in T2
with established CVD

73. ADA/EASD recommendation (2019 update)

74. C&H blood glucose management for
type 2 adults in primary care
• To be resubmitted to Joint Prescribing Group in Sept for approval
• Contents:
 HbA1c targets
 Pathway – similar to NICE algorithm but refer to ADA/EASD recommendation
for patients with established ASCVD, CKD or HF
 Additional info for meds in C&H Joint Formulary
 Renal and hepatic impairment
 NICE Patient Decision Aid
 Checklist for initiating SGLT2 inhibitors
• Will need regular update – NICE T2 guideline due to be updated in 2021

75. C&H blood glucose management for type 2 adults in primary care

76. C&H blood glucose management for type 2 adults in primary care

77. C&H blood glucose management for type 2 adults in primary care

78. C&H blood glucose management for type 2 adults in primary care

79. What to discuss with T2 patients at
medication review
• Recent blood results (compare with previous results) and explain the significance
• Remind the patient complications from diabetes
• Agree with the patient how to improve health outcomes, including lifestyle changes,
important to discuss diet
• Review treatment, check adherence, understanding of instruction and timing, reminder
chart might be useful (MaPPs)
• Go through insulin counselling points if on insulin
• Check timing of insulin, storage, frequency of changing needles, disposal of needles,
quantity
• Any hypo episodes if on sulfonylureas or repaglinide or insulins, check understanding of
hypo symptoms and treatment
• Self-monitoring of blood glucose and check readings if meter available
• Summarise agreed changes and when to review

80. Wastage

81. Useful websites and references
• Diabetes UK www.diabetes.org.uk
• Diabetes.co.uk www.diabetes.co.uk
• C&H https://gps.cityandhackneyccg.nhs.uk/
• Diabetes: evidence-based management e-learning www.cppe.org.uk
• Trend UK https://trend-uk.org/
• Sugar equivalent infographics https://phcuk.org/sugar/
• Management of hyperglycaemia in type 2 diabetes – a consensus report by ADA and
EASD https://link.springer.com/content/pdf/10.1007/s00125-019-05039-w.pdf
• Diabetes on the net www.diabetesonthenet.com – access to journals and education
for HCP
• Cambridge diabetes education programme https://www.cdep.org.uk/home.html