Learn more about the 2022 NICE guideline NG28 update using the self-guided CPD-accredited Cardiorenal Protection module, which gives you all the data you need to help contextualise the changes and build a strong understanding of how these changes will impact your day-to-day practice and improve outcomes for your patients with T2D. (Approx. 10 mins)

1. AN UPDATE TO NICE GUIDELINE NG28
This is an AstraZeneca promotional material for UK healthcare professionals only.
Prescribing information for can be found here.
GB-38766 | October 2022
Visit the See Beyond Sugar webpage to learn more about managing
cardiorenal risk in type 2 diabetes and improving patient outcomes >
Adverse events should be reported. Reporting forms and information can be found at
www.mhra.gov.uk/yellowcard. Adverse events should also be reported to AstraZeneca by
visiting https://aereporting.astrazeneca.com or by calling 0800 783 0033.
CARDIORENAL PROTECTION:
A RISK-BASED APPROACH TO MANAGING TYPE 2 DIABETES
IN ADDITION TO GLYCAEMIC CONTROL

2. FORXIGA® (dapagliflozin) | Therapeutic indication
Type 2 diabetes mellitus
FORXIGA is indicated in adults and children aged 10 years and above for the treatment of insufficiently controlled
type 2 diabetes mellitus as an adjunct to diet and exercise
• as monotherapy when metformin is considered inappropriate due to intolerance.
• in addition to other medicinal products for the treatment of type 2 diabetes.
For study results with respect to combination of therapies, effects on glycaemic control, cardiovascular events, and
the populations studied, see sections 4.4, 4.5 and 5.1. of the summary of product characteristics
Heart failure
FORXIGA is indicated in adults for the treatment of symptomatic chronic heart failure with reduced ejection fraction.
Chronic kidney disease
FORXIGA is indicated in adults for the treatment of chronic kidney disease
FORXIGA® (dapagliflozin) Indication:
Summary of key data

3. Finding your way
(a)CV(D) = (atherosclerotic) cardiovascular (disease); CKD = chronic kidney disease; HF = heart failure; NG28 = NICE guideline 28; NICE = National Institute for Health and Care Excellence;
SGLT2i(s) = sodium-glucose cotransporter-2 inhibitor(s); T2D = type 2 diabetes.
Welcome and introduction
• Recognise the burden and consequences of cardiorenal disease (HF, aCVD, renal impairment leading
to CKD) as early complications in T2D
• Examine the SGLT2i class in terms of cardiorenal benefit
• Understand the NG28 guideline update ‒ from primarily addressing blood glucose control to a risk-
based approach in T2D
• Review implementation of risk assessment in existing- and newly-diagnosed patients to optimise their
T2D treatment
• Identify which patients require first-line treatment with an SGLT2i in combination with metformin
Key objectives
This presentation examines the optimal drug treatment for T2D, supported
by the 2022 NICE guideline NG28 update
• Clinical trials showed that SGLT2is reduced the risk of CKD progression, mortality and CV events
in T2D
• The NICE committee agreed that it is important to assess CV status to help determine suitable
treatments; NG28 recommendations have been updated to reflect this
SGLT2i Prescribing considerations Guidelines Summary
T2D burden
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Clinical practice points highlight
practical advice related to
patient care
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4. The burden of cardiorenal disease and T2D
Cardiorenal diseases account for 60% of first comorbidities in T2D:1–3
CKD = chronic kidney disease; HF = heart failure; LV = left ventricular; MI = myocardial infarction; PAD = peripheral arterial disease; T2D = type 2 diabetes.
1. NHS. End of life care in heart failure. https://www.england.nhs.uk/improvement-hub/wp-content/uploads/sites/44/2017/11/heart-failure.pdf Accessed April 2022; 2. Kidney Care UK. Facts and Stats.
https://www.kidneycareuk.org/news-and-campaigns/facts-and-stats/ Accessed April 2022; 3. Birkeland KI et al. Diabetes Obes Metab. 2020;22:1607–1618; 4. Diabetes UK. Diabetes diagnoses double in the last 15
years. https://www.diabetes.org.uk/about_us/news/diabetes-diagnoses-doubled-prevalence-2021 Accessed April 2022; 5. Lawson CA et al. JAMA Netw Open 2019;2:e1916447; 6. Parving HH et al. Kidney Int
2006;69:2057–2063.
HF
2021 UK
prevalence1
~900,000
CKD
2021 UK
prevalence2
~3M
58% of people with T2D
will develop CKD
(N=24,151)6
24% of HF patients in
a UK primary care
cohort had T2D
(N=87,709)5
2021 UK
prevalence4
~4.9M
Diabetes can affect the
heart and kidneys
simultaneously and is an
independent predictor of
worsening function
Diabetes
Renal impairment (leading
to CKD) and HF are
interrelated and lead to a
vicious circle of cardiac,
renal and metabolic risk
Cardiorenal
diseases
(HF or CKD)
60%3
Prescribing considerations Guidelines
SGLT2i
Home T2D burden Summary

5. 0
500
1000
1500
2000
2500
3000
3500
T2D costs ~10% of the overall NHS budget, with 80%
of direct costs spent on complications1,2
CVD = cardiovascular disease; HF = heart failure; MI = myocardial infarction; NHS = National Health Service; QoL = quality of life; T2D = type 2 diabetes.
1. ©NICE [2022] Type 2 diabetes in adults: management. Available from www.nice.org.uk/guidance/ng28 All rights reserved. Subject to Notice of rights. NICE guidance is prepared for the National Health Service in
England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication; 2. Diabetes UK. The cost of diabetes
report 2014. https://www.diabetes.org.uk/resources-s3/2017-11/diabetes%20uk%20cost%20of%20diabetes%20report.pdf Accessed April 2022. 3. Hex N, et al. Diabet Med 2012;29:855–862.
Cardiorenal complications are amongst the largest costs2
Adapted from Diabetes UK. 20102
0
2
4
6
8
10
12
14
16
2010/2011 2035/2036
£8.8 B
£15.1 B
T2D costs are set to rise dramatically over the
next 15 years3
Direct
costs
of
T2D
care
(£Billion)
Adapted from Hex, et al. 20123
72% increase
Total: £7.7 Billion
Cost
to
healthcare
services
(£Million)
Prescribing considerations Guidelines
SGLT2i
Home T2D burden Summary
Cardiorenal complications
MI, HF, other CVD
Excess inpatient days
Kidney failure,
kidney-related costs
Neuropathy
Stroke
Foot ulcers, amputations
Other

6. Previously, the primary focus of T2D management has
been on glycaemic control (HbA1c)
CV = cardiovascular; eGFR = estimated glomerular filtration rate; HbA1c = haemoglobin A1c; HF = heart failure; NG28 = NICE guideline 28; NICE = National Institute for Health and Care Excellence;
SGLT2i(s)= sodium-glucose cotransporter-2 inhibitor(s); T2D = type 2 diabetes.
1. NICE Type 2 diabetes in adults: management (NG28). Published December 2015; updated November 2021; 2. ©NICE [2022] Type 2 diabetes in adults: management. Available from
www.nice.org.uk/guidance/ng28 All rights reserved. Subject to Notice of rights. NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be
updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication.
Glucose lowering
alone has minimal
impact on reducing
HF events
• treatment for T2D based on blood glucose levels (HbA1c) with
SGLT2is used in dual therapy or triple therapy only when
metformin or sulphonylurea are contraindicated or not tolerated
• cardiorenal risk should be managed separately in parallel with
glycaemic treatment
NG28 2022: in addition to blood glucose control, management of
cardiorenal risk is now recognised to be of equal significance
based on recently published evidence of positive CV outcomes in T2D2
• First-line metformin, based on
HbA1c targets
• Intensification to dual and triple
therapy
• Anti-hypertensives
• Cholesterol reduction
• Lifestyle modification
Previous NICE guidelines (November 2021 update)
recommend:1
Benefits of glucose-
lowering are less
clear in eGFR
<60 mL/min/1.73 m2
Prescribing considerations Guidelines
SGLT2i
Home T2D burden Summary

7. In a systematic review of 57 studies (N=4,549,481), CVD
affected 32% overall, specifically:2
Cardiorenal disease is the most frequent first
comorbidity in T2D1
NICE define established aCVD as coronary heart disease, acute coronary syndrome, previous MI, stable angina, prior coronary or other revascularisation, cerebrovascular disease (ischaemic stroke and transient
ischaemic attack) and peripheral arterial disease3
(a)CV(D) = (atherosclerotic) cardiovascular (disease); CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate; HF = heart failure; MACE = major adverse cardiovascular event;
MI = myocardial infarction; T2D = type 2 diabetes.
1. Birkeland KI et al. Diabetes Obes Metab 2020;22:1607–1618; 2. Einarson TR et al. Cardiovasc Diabetol 2018;17:83; 3. Hill CJ et al. Diabet Med 2014;31:448–454 4. Kidney Disease: Improving Global Outcomes
(KDIGO). KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int 2013;3:1–150.
Adapted from Einarson TR et al. 20182
In the UK National Diabetes Audit (N=868,616),
42% of patients with T2D had renal impairment
(normal function: eGFR >60 mL/min/1.73 m2 + normal albumin:
creatinine ratio)3
CV death risk
Stage of CKD
(eGFR mL/min/1.73 m2)
Up to 4.3x greater 3a (45–60)
Up to 5.2x greater 3b (30–45)
Up to 14x greater 4 (15–30)
Adapted from KDIGO 20124
CV mortality risk compared to an eGFR baseline of 90–105 mL/min/1.73 m2 and ACR
<10. CV mortality ranges: Stage 3a (1.5 to 4.3), Stage 3b (2.2 to 5.2), Stage 4 (4.8 to
14.0) per year4
Atherosclerosis
HF
Angina
MI
Stroke
Rate
(%)
Prescribing considerations Guidelines
SGLT2i
Home T2D burden Summary
Declining eGFR strongly correlates with MACE and
CV death4
CV outcome
29
15 15
10
8
0
5
10
15
20
25
30

8. In T2D, even early decline of eGFR (≤75 mL/min/1.73 m2)
is associated with an increased risk of death
eGFR = estimated glomerular filtration rate; T2D = type 2 diabetes.
Fox C et al. Lancet 2012;380:1662–1673.
Risk of all-cause mortality according to eGFR in patients with T2D
Prescribing considerations Guidelines
SGLT2i
Home T2D burden Summary

9. (a)CV(D) = (atherosclerotic) cardiovascular (disease); ARR = absolute risk reduction; CANVAS = Canagliflozin Cardiovascular Assessment Study; CANVAS-R = Canagliflozin Cardiovascular Assessment Study-
Renal; CI = confidence interval; CREDENCE = Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation; DECLARE-TIMI 58 = Dapagliflozin Effect on Cardiovascular Events–
Thrombolysis in Myocardial Infarction 58; EMPA-REG-OUTCOME = Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients; HF = heart failure;
hHF = hospitalisation for HF; HR = hazard ratio; MACE = major adverse cardiovascular event; MI = myocardial infarction; SGLT2i(s) = sodium-glucose cotransporter-2 inhibitor(s);
VERTIS CV = Cardiovascular Outcomes Following Ertugliflozin Treatment in Type 2 Diabetes Mellitus Participants With Vascular Disease.
McGuire DK et al. JAMA Cardiol 2021;6:148–158.
Cardiorenal benefits demonstrated in meta-analysis
of SGLT2i trials assessing CV and kidney outcomes
• A meta-analysis of six SGLT2i trials (EMPA-REG OUTCOME, CANVAS, CANVAS-R, DECLARE-TIMI 58, CREDENCE,
VERTIS CV) (N=46,969; 66.2% with aCVD; 7.4%–59.8% with baseline eGFR <60 mL/min/1.73 m2; 10.0%–23.7% with history of
HF) reported favourable CV and kidney outcomes
10% hazard reduction
HR 0.90 (95% CI 0.85–0.95)
22% hazard reduction
HR 0.78 (95% CI 0.73–0.84)
4931 MACE
(MI, stroke and CV death)
3154 CV deaths/hHF 1426 renal composite outcomes
38% hazard reduction
HR 0.62 (95% CI 0.56–0.70; p<0.0001)
0.4% ARR 1.3% ARR 1.4% ARR
• Presence or absence of aCVD did not modify the above treatment outcomes
SGLT2i Prescribing considerations Guidelines
Home T2D burden Summary

10. Dapagliflozin addresses the cardiorenal burden
across HF and CKD
ACEi = angiotensin-converting-enzyme inhibitor; ARB = angiotensin receptor blocker; ARR = absolute risk reduction; CI = confidence interval; CKD = chronic kidney disease; CV = cardiovascular; DAPA-CKD = Dapagliflozin
and Prevention of Adverse Outcomes in Chronic Kidney Disease; DAPA-HF = Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure; eGFR = estimated glomerular filtration rate; DECLARE = Dapagliflozin
Effect on Cardiovascular Events; ESKD = end-stage kidney disease; GLT = glucose-lowering therapy; HF = heart failure; hHF = hospitalisation for heart failure; HR = hazard ratio; MACE = major adverse CV events;
RRR = relative risk reduction; T2D = type 2 diabetes.
1. Wiviott SD et al. N Engl J Med 2019;380:347–357; 2. Mosenzon O et al. Lancet Diabetes Endocrinol 2019;7:606–617; 3. McMurray JJV et al. N Engl J Med 2019;381:1995–2008; 4. Petrie MC et al. JAMA
2020;323:1353–1368; 5. Docherty KF et al. Article and supplementary material. Diabetes Care 2020;43:2878–2881; 6. Heerspink HJL et al. N Engl J Med 2020:383;1436–1446.
Dapagliflozin vs placebo
Dapagliflozin vs placebo
(+ device therapy, HF- and
other glucose-lowering
medications)
Dapagliflozin vs placebo
(± ACEi or ARB)
SGLT2i Prescribing considerations Guidelines
Home T2D burden Summary

11. Dapagliflozin has shown an overall consistent safety
profile in patients with T2D, CKD and HFrEF
*Acute kidney injury in DECLARE-TIMI 58; †Definite or probable; ‡Leading to discontinuation of the trial regimen or considered to be serious adverse events.
CKD = chronic kidney disease; DAPA = dapagliflozin; DAPA-CKD = Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease; DAPA-HF = Dapagliflozin and Prevention of Adverse Outcomes in
Heart Failure; eGFR = estimated glomerular filtration rate; DECLARE-TIMI 58 = Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction 58; DKA = diabetic ketoacidosis;
HFrEF = heart failure with reduced ejection fraction; N/A = not available; T2D = type 2 diabetes.
1. Wiviott SD et al. Article and supplementary material. N Engl J Med 2019;380:347–357; 2. Heerspink HJL et al. N Engl J Med 2020:383:1436–1446; 3. McMurray JJV et al. Article and supplementary material. N
Engl J Med 2019;381:1995–2008; 4. In House Data, AstraZeneca Pharmaceuticals LP. Clinical study report D1699C00001.
All values are % unless otherwise stated
Note: Adverse event rates should not be compared across the 3 trials due to the different patient populations and follow-up durations.
SGLT2i Prescribing considerations Guidelines
Home T2D burden Summary
DECLARE-TIMI 581 DAPA-CKD2 DAPA-HF3,4
Adverse event, %
DAPA 10 mg
(N=8574)
Placebo
(N=8569)
DAPA 10 mg
(N=2149)
Placebo
(N=2149)
DAPA 10 mg
(N=2368)
Placebo
(N=2368)
Volume depletion 2.5 2.4 5.9 4.2 7.5 6.8
Renal adverse event* 1.5 2.0 7.2 8.7 6.5 7.2
Fracture 5.3 5.1 4.0 3.2 2.1 2.1
Amputation 1.4 1.3 1.6 1.8 0.5 0.5
Major hypoglycaemia 0.7 1.0 0.7 1.3 0.2 0.2
Diabetic ketoacidosis† 0.3 0.1 0 <0.1 0.1 0
Genital infection‡ 0.9 0.1 NA NA 0.3 <0.1
Urinary tract infection‡ 1.5 1.6 NA NA 0.8 0.9
Fournier’s gangrene, n 1 5 0 1 0 1

12. Prescribing considerations in T2D
DKA = diabetic ketoacidosis; eGFR = estimated glomerular filtration rate; GI = gastrointestinal; SGLT2i(s) = sodium-glucose cotransporter-2 inhibitor(s); SU = sulphonylurea.
Electronic Medicines Compendium. Dapagliflozin Summary of Product Characteristics. May 2022. https://www.medicines.org.uk/emc/product/7607/smpc#gref Accessed September 2022.
Observation Action
Rare cases of DKA, including life-threatening and fatal cases, have
been reported in patients treated with SGLT2is, including dapagliflozin
If DKA is suspected or diagnosed, dapagliflozin treatment should be stopped
immediately
Insulin and SUs cause hypoglycaemia A lower dose of insulin/SU may be required to reduce the risk of
hypoglycaemia when used in combination with dapagliflozin
There is limited experience with initiating dapagliflozin in patients with
eGFR <25 mL/min/1.73 m2, and no experience with initiating treatment
in patients with eGFR <15 mL/min/1.73 m2
It is not recommended to initiate dapagliflozin in patients with eGFR
<15 mL/min/1.73 m2
Whilst cardiorenal protection is maintained, glycaemic efficacy is
reduced in patients with eGFR <45 mL/min/1.73 m2
Additional glucose lowering treatment should be considered if eGFR drops
below 45 mL/min/1.73 m2
Volume depletion may be exacerbated in patients on diuretics,
antihypertensives or the elderly
Exercise caution in these patients and consider adjusting the dose of diuretic
medication if needed
Intercurrent conditions may lead to volume depletion (e.g. GI illness) Careful monitoring of volume status (e.g. physical examination, blood pressure
measurements, laboratory tests) is recommended
Interrupt therapy/withhold in patients with confirmed volume depletion, until
volume depletion is corrected
Please refer to the product Summary of Characteristics for full details
Prescribing considerations
Home T2D burden Guidelines
SGLT2i Summary

13. NICE GUIDELINE NG28 NOW
RECOMMENDS FIRST-LINE
SGLT2i + METFORMIN ON A
RISK-BASED APPROACH
ADOPT AN INDIVIDUALISED APPROACH TO T2D CARE:
INCLUDE CVD STATUS AND RISK ASSESSMENT
CVD = cardiovascular disease; NG28 = NICE guideline 28; NICE = National Institute for Health and Care Excellence; SGLT2i(s) = sodium-glucose cotransporter-2 inhibitor(s); T2D = type 2 diabetes.
Click here to take a closer look at the
NG28 guideline
Guidelines
Home T2D burden SGLT2i Summary
Prescribing considerations

14. CV(D) = cardiovascular (disease); DPP-4 = dipeptidyl peptidase 4; GI = gastrointestinal; HbA1c = haemoglobin A1c; MR = modified release; NG28 = NICE guideline 28; NICE = National Institute for Health and Care Excellence; SGLT2 = sodium-glucose cotransporter-2;
TA = technology appraisal.
© NICE 2022 Type 2 diabetes in adults: management. Available from www.nice.org.uk/guidance/ng28 All rights reserved. Subject to Notice of rights.
NICE guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication.
Rescue therapy
For symptomatic hyperglycaemia, consider insulin or a sulfonylurea and review when blood glucose control has been achieved.
Click on the links
for further
information
about the
recommendations
For easy
navigation of the
complete NG28
guideline, try
using the
NG28 explorer

15. (a)CV(D) = (atherosclerotic) cardiovascular (disease); CKD = chronic kidney disease; eGFR = estimated glomerular filtration rate; HbA1c = haemoglobin A1c; HF = heart failure; SGLT2i(s) = sodium-glucose cotransporter-2 inhibitor(s);
T2D = type 2 diabetes.
1. NHS. End of life care in heart failure. https://www.england.nhs.uk/improvement-hub/wp-content/uploads/sites/44/2017/11/heart-failure.pdf Accessed April 2022; 2. Kidney Care UK. Facts and Stats. https://www.kidneycareuk.org/news-and-
campaigns/facts-and-stats/ Accessed April 2022; 3. Birkeland KI et al. Diabetes Obes Metab. 2020;22:1607–1618; 4. Einarson TR et al. Cardiovasc Diabetol 2018;17:83; 5. Rawshani A et al. N Engl J Med 2018;379:633–644; 6. Fox CS et al. Lancet
2012;380:1662–1673; 7. Matsushita K et al. Lancet Diabetes Endocrinol 2015;3:514–525; 8. ©NICE [2022] Type 2 diabetes in adults: management. Available from www.nice.org.uk/guidance/ng28 All rights reserved. Subject to Notice of rights. NICE
guidance is prepared for the National Health Service in England. All NICE guidance is subject to regular review and may be updated or withdrawn. NICE accepts no responsibility for the use of its content in this product/publication; 9. McGuire DK et
al. JAMA Cardiol 2021;6:148–158.
Summary
Heart and renal complications in
T2D, such as HF, aCVD and renal
impairment leading to CKD, are
common and associated with
significant morbidity and high
mortality risk1–4
HbA1c control alone does not
remove the risk of diabetic HF
events or CKD development5,6
Declining eGFR is associated with increased risk of aCVD and HF,7
therefore proactively managing your patients’ risk for HF, aCVD
and renal disease is equally as important as glycaemic control8
SGLT2-is demonstrate proven cardiorenal benefits9
• Offer first-line an SGLT2i with proven CV benefit
(+ metformin) for patients with HF or established aCVD8
• Consider SGLT2i with proven CV benefit (+ metformin) in your
patients at high risk of CVD (QRISK®2 >10%)8
Summary
Prescribing considerations
Home T2D burden SGLT2i Guidelines
Access
supporting
materials:
Taking the
risk-based approach
Use the NG28 explorer
to aid in providing an
individualised
approach for your
patients