Dr Umesh Dashora and colleagues from the CaReMeUK Partnership outline guidance on how to manage type 2 diabetes with cardiovascular and renal disease

DASHORA, Umesh_WEB

Dr Umesh Dashora

Read this article to learn more about:

  • the need for joined-up guidance to improve the management of people with diabetes, cardiovascular disease (CVD), and renal disease
  • the positioning of sodium–glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in the holistic management of diabetes in 2021
  • factors to consider when initiating second-line therapies.

A version of this article, adapted for a secondary-care audience, was published in Clinical Medicine 2021; 21: 204–210.

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In people with diabetes, the presence of multiple co-morbidities—such as cardiovascular disease (CVD), renal dysfunction, and metabolic disease—is common,1,2 and the prevalence of cardiovascular multimorbidity has significantly increased in modern times.3 Unfortunately, the management of these conditions remains fragmented between different specialties, and there is often a gap in communication between healthcare professionals about the care of individuals with these problems. Thus, there is an urgent need to develop a joined-up approach.

The Cardio-Renal-Metabolic (CaReMeUK) Partnership is a collaboration between the British Cardiovascular Society, the Renal Association, and the Association of British Clinical Diabetologists. These three professional societies—along with the Primary Care Cardiovascular Society and the Primary Care Diabetes Society—have formed the CaReMe UK Partnership, bringing together expertise from across primary and secondary care with the aim of improving the management of people with multiple co-morbidities.

Recent cardiovascular (CV) outcomes trials have established the significant CV and renal benefits of sodium–glucose co-transporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs).4–19 The American Diabetes Association/European Association for the Study of Diabetes (EASD) and the European Society of Cardiology/EASD have already prioritised the use of SGLT2is and GLP-1 RAs in certain patient groups (such as those with atherosclerotic CVD, heart failure, or chronic kidney disease [CKD]) in their recommended treatment algorithms.20–22 NICE guidelines for the management of people with type 2 diabetes date from 2015 and do not take into account the data from recent cardiovascular outcomes trials, although NICE is due to publish an update in future.23

The CaReMeUK Partnership met virtually many times to discuss the recent evidence. After much deliberation, the group agreed on a number of algorithms and guides for healthcare professionals to improve the management of people with diabetes, CVD, and renal disease, and a leaflet and booklet for people with diabetes on appropriate and safe use of medications.24

This article explains the CaReMeUK Partnership consensus guidance on the management of people with type 2 diabetes, based on the current evidence.

The importance of diagnosing the type of diabetes correctly

Diabetes is diagnosed by a fasting plasma glucose level of ≥7 mmol/l or a glycated haemoglobin (HbA1c) level of ≥48 mmol/mol on one occasion in the presence of symptoms, or on two occasions in asymptomatic people.25

People with type 1 diabetes are dependent on insulin for their survival. It is important to make an accurate distinction between type 1 and type 2 diabetes because those who have the former are at high risk of diabetic ketoacidosis (DKA) and harm if their insulin is reduced or stopped, and treatment is with SGLT2is or GLP-1 RAs only.

If a person with apparent type 2 diabetes does not have the typical phenotype or characteristics of type 2 diabetes (for example, overweight, late onset), specialist advice may be needed to exclude the diagnosis of type 1 diabetes (by antibody tests and C-peptide levels).

People with type 2 diabetes have significant endogenous insulin production, but are characterised by high insulin resistance and are at high risk of CV and renal disease; in the case of CV co-morbidities, an almost twofold increase in the risk of mortality and a reduction in life expectancy of around 12 years were evident in patients aged 60 years with any two of the following conditions: diabetes mellitus, stroke, and myocardial infarction (MI).26 People with type 1 diabetes are also at increased risk of cardiac and renal complications compared with the general population,27–29 but the number of people living with type 1 diabetes is lower, and the resultant economic burden can be expected to be smaller, than that of people with type 2 diabetes.30

The need for a cardio-renal-metabolic pathway for the management of diabetes, CVD, and renal disease

Clinical outcomes for most patients with CVD have improved substantially over time, but outcomes in patients with CVD and diabetes remain poorer than those without diabetes—for example, improvements in the management of MI in recent decades have not reduced the gap in outcomes following MI between patients with and without diabetes.31 A glucose-based approach to the management of diabetes has only a modest impact on the risk of macrovascular events, and causes no significant reduction in CV mortality.32

SGLT2is improve CV and renal outcomes.4–12 A number of SGLT2is are recommended by guidelines and have received licences for indications such as heart failure and renal impairment. Based on clinical trial data, many of these drugs are indicated in people with risk factors or established CV or renal disease, irrespective of their HbA1c or diabetic status and estimated glomerular filtration rate (eGFR). SGLT2is may not be suitable for a minority of people with type 2 diabetes;33,34 please check the up-to-date licences and Summaries of Product Characteristics (SPCs).35–38

GLP-1 RAs also reduce major adverse CV events, hospitalisation for heart failure, and poor renal outcomes.13–19 Recognition of the major CV and renal benefits of these drugs has led to a change in the focus of international guidelines, in which SGLT2is and GLP-1 RAs are now prioritised ahead of other glucose-lowering therapies, regardless of HbA1c thresholds, in patients with type 2 diabetes and CVD.20–22

However, data from the National Diabetes Audit suggest that targets for glycaemia, blood pressure, and lipids are met in only a minority of individuals,39 indicating room for improvement in the management of diabetes and co-morbidities. In one hospital, an audit of patients with type 2 diabetes 1 year after hospital admission for MI found that HbA1c was above target in more than half of these patients; most were eligible for treatment with an SGLT2i or GLP-1 RA, but were not receiving one of these agents.40

In contrast to international diabetes guidelines, current NICE guidance on the management of type 2 diabetes in adults was published in 2015, and has not yet been updated to reflect the accumulating evidence for CV risk reduction.23 In many regions, local guidelines are now similarly outdated, highlighting the pressing need for individual regions across the UK to develop and implement their own cardiometabolic pathways. Until updated diabetes guidance is available from NICE, local initiatives are needed to drive improvements in CV risk management in patients with diabetes.

Supplementing a traditional ‘glycaemia-based’ diabetes management pathway with a cardiometabolic pathway focused on increasing uptake of SGLT2is and GLP-1 RAs, irrespective of HbA1c, has the potential to reduce CV events and mortality.4–19 Treatment recommendations should be evidence-based, and CV and renal risk reduction must override other considerations, such as acquisition cost. In this setting, the acquisition cost of SGLT2is is similar to that of the most commonly prescribed alternative, dipeptidyl peptidase-4 inhibitors (DPP-4is).41 Modelling based on the local population can reflect the downstream cost savings resulting from a reduction in costly clinical events (primarily admissions for heart or kidney failure) afforded by SGLT2i therapy. The cost-effectiveness of treatment with empagliflozin and dapagliflozin, taking into account the reduction in clinical events, has been considered by NICE in its related Technology Appraisals.42,43

Key guidance

The management of asymptomatic individuals with type 2 diabetes, taking into account recent data from CV outcome trials, is presented in an algorithm in Figure 1.

CaReMe antidiabetic treatment algorithm_ONLINE

Figure 1: Management of asymptomatic people with type 2 diabetes[A]

Table 1: Summary of licensed indications and recommended doses of SGLTis in type 2 diabetes34
 Dose adjustment recommendations based on kidney function ml/min/1.73 m2

SGLT2i

Licensed indication

eGFR >60 

eGFR 45–59 

eGFR 30–44 

eGFR <30 

Canagliflozin35

Adults with insufficiently controlled type 2 diabetes

Initiate 100 mg; titrate to 300 mg if needed

Initiate/continue with 100 mg only

Initiate/continue with 100 mg only if urinary albumin:creatinine ratio >300 mg/g

Continue at 100 mg for reno-protection until dialysis/transplant

Dapagliflozin36

Adults with insufficiently controlled type 2 diabetes

Initiate 10 mg

Continue with 10 mg for reno-protection only. Do not initiate

Not recommended

HFrEF with or without type 2 diabetes

Initiate 10 mg

Limited experience

Empagliflozin37

Adults with insufficiently controlled type 2 diabetes

Initiate 10 mg; titrate to 25 mg if required

Continue with 10 mg only. Do not initiate

Not recommended

Ertugliflozin38

Glycaemic control only

Initiate 5 mg; titrate to 15 mg if needed

Continue with 5 mg or 15 mg. Do not initiate

Not recommended

Key: green=initiate; yellow=initiate in certain circumstances; orange=do not initiate but can continue established treatment; red=treatment not recommended

In appropriate high-risk patients, a decision to treat with an SGLT2i to reduce the risk of CV, kidney, and/or heart failure events should be considered independently of HbA1c:

  • canagliflozin and empagliflozin have been shown to reduce MACE in clinical trials35,37
  • canagliflozin, dapagliflozin, and empagliflozin have been shown to reduce hospitalisation for heart failure and achieve some reduction in CKD progression in CV trials4–6
    • canagliflozin and dapagliflozin have primary renal outcome data9,10
    • canagliflozin is now licensed for the treatment of DKD in type 2 diabetes35
    • dapagliflozin and empagliflozin have primary heart failure outcome data11,12
    • dapagliflozin is now licensed for—and is the subject of a NICE Technology Appraisal on—the treatment of HFrEF in people with or without type 2 diabetes.11,43 When used in people with a GFR <45 mmol/mol, the effect on glucose lowering is likely to be minimal or absent,52 but the medication is still indicated for people with HFrEF.36

Further trial results on CKD and heart failure are in the pipeline, which may impact licensed indications in future. Please refer to the current SPCs for individual drugs for the latest information on licensed indications and dose-adjustment recommendations.

SGLT2i=sodium–glucose co-transporter-2 inhibitor; eGFR: estimated glomerular filtration rate; HFrEF=heart failure with reduced ejection fraction; CV=cardiovascular; HbA1c =glycated haemoglobin; MACE=major adverse cardiovascular events; CKD=chronic kidney disease; DKD=diabetic kidney disease; GFR=glomerular filtration rate; SPC=Summary of Product Characteristics

Adapted with permission from Umesh D, Gregory R, Winocour P et al. Association of British Clinical Diabetologists (ABCD) and Diabetes UK joint position statement and recommendations for non-diabetes specialists on the use of sodium glucose co-transporter 2 inhibitors in people with type 2 diabetes (January 2021). Clin Med 2021; 21 (3): 1–7.

Box 1: Who is the ideal candidate for SGLT2i treatment?34

It is important to select the right patient for SGLT2i therapy and to avoid it in others who may be at high risk of DKA.33,34 The following patients are likely to benefit most:

  • Adults aged >18 years with type 2 diabetes and one or more of the following:
    • established/high risk of CVD46
    • CKD with albuminuria9,10
    • history of heart failure with reduced ejection fraction11,12
    • inadequate glycaemic control with a need to minimise hypoglycaemia3538
    • inadequate glycaemic control with a need to minimise weight gain or encourage weight loss3538
  • Patients with a clear understanding of the risks associated with SGLT2is and how to reduce them.

SGLT2i=sodium–glucose co-transporter-2 inhibitor; DKA=diabetic ketoacidosis; CVD=cardiovascular disease; CKD=chronic kidney disease

Box 2: When to exercise caution when using an SGLT2i34,51

SGLT2is should be used with caution in the following situations:

  • in people adhering to a ketogenic diet
  • in those with a BMI <25 kg/m2 (<23 kg/m2 in people of South-Asian descent)
  • in people considered at high risk of acute effects of hyperglycaemia, such as in those with dehydration due to non-adherence to medication
  • in individuals with a very high HbA1c (>86 mmol/mol [~10% in old HbA1c units])
  • in people diagnosed with, or at risk of, frailty
  • in cognitive impairment, which may interfere with an individual’s ability to identify and prevent DKA
  • in people on chronic oral steroids
  • in those who have experienced recent weight loss
  • in patients with a long duration of diabetes (generally >10 years from diagnosis).

SGLT2is should be avoided in the following situations:

  • in people with a history of DKA
  • in individuals with an eating disorder
  • when eGFR is lower than permitted by the up-to-date licence of the medication being considered
  • with excess alcohol consumption or intravenous drug use
  • in those with an acute medical illness, including COVID-19, or those requiring surgery or a planned medical procedure
  • in people with any diagnosis or suspicion of diabetes due to other causes, including type 1 diabetes,[A] LADA, other genetic causes of diabetes, or known pancreatic disease or injury, or in people who rapidly progressed to needing insulin within 1 year of diagnosis
  • in pregnant or breastfeeding women, women in their child-bearing years, and women who are sexually active without contraception
  • in people aged <18 years
  • with suspected type 1 diabetes, except under specialist supervision (dapagliflozin 5 mg only)[A]
  • in patients with an acute vascular event who are not stable.

Seek advice from the local diabetes team if unsure about the benefits and risks

[A] Dapagliflozin 5 mg is licensed for use in type 1 diabetes in certain circumstances, but should only be initiated and supervised by a specialist36

SGLT2i=sodium–glucose co-transporter-2 inhibitor; BMI=body mass index; HbA1c =glycated haemoglobin; DKA=diabetic ketoacidosis; eGFR=estimated glomerular filtration rate; LADA=latent autoimmune diabetes

Adapted with permission from Umesh D, Gregory R, Winocour P et al. Association of British Clinical Diabetologists (ABCD) and Diabetes UK joint position statement and recommendations for non-diabetes specialists on the use of sodium glucose co-transporter 2 inhibitors in people with type 2 diabetes (January 2021). Clin Med 2021; 21 (3): 1–7.

Table 2: Summary of current licensed indications and recommended doses of GLP-1 RAs in type 2 diabetes[A]
 Dose adjustment recommendations based on kidney function ml/min/1.73 m2

GLP-1 RAs

Licensed indication

eGFR >60

eGFR 45–59

eGFR 30–44

eGFR <30

eGFR <15

Lixisenatide45,53

Adults with inadequately controlled type 2 diabetes on OAD or basal insulin or both

Starting dose 10 mcg (day 1–14)

Maintenance dose 20 mcg

 

Caution: eGFR 30–50ml/min/1.73 m2

 

Liraglutide46

Type 2 diabetes mellitus—monotherapy (if metformin inappropriate) or in combination with other antidiabetic drugs

Starting dose: 0.6 mg once daily for a week

Maintenance dose: 1.2 or 1.8 mg daily

   

Semaglutide47

Type 2 diabetes mellitus monotherapy (if metformin inappropriate) or in combination with other antidiabetic drugs

Starting dose: 0.25 mg once weekly for 4 weeks

Maintenance dose 0.5–1 mg once weekly

   

Exenatide QW48

Type 2 diabetes mellitus in combination with metformin or an SU or both, or with TZD, or with both metformin and TZD in people not achieving glycaemic control

2 mg once weekly

  Avoid if eGFR <30 ml/min/1.73 m2

Dulaglutide49

Type 2 diabetes mellitus—monotherapy (if metformin inappropriate) 0.75 mg or in combination with other antidiabetic drugs if inadequately controlled 1.5–4.5 mg once weekly

   

Oral semaglutide50

Type 2 diabetes mellitus—monotherapy (if metformin inappropriate) or in combination with other antidiabetic drugs

Starting dose: 3 mg once daily for 1 month

Maintenance dose 7–14 mg once daily

   
Key: green=suitable for use; yellow=use with caution; red=treatment not recommended
[A] Consult individual SPCs because the licensed indications may have changed since the production of this table
GLP-1 RA=glucagon-like peptide-1 receptor agonist; eGFR=estimated glomerular filtration rate; OAD=oral antidiabetic agent; QW=once weekly; SU=sulfonylurea; TZD=thiazolidinedione; SPC=Summary of Product Characteristics
Table 3: Common adverse reactions to SGLT2is34–38
Adverse reactionFrequencyNotes

Genital mycotic infections

Common/very Common

Men and women. Provide genital hygiene advice. Most initial cases can be treated with topical antifungals and won’t recur. Consider reviewing therapy for recurrent infections

Increased urination

Common

Increased frequency and/or increased volume

Urinary tract infections

Common

In recent large trials, any increase in risk was small and non-significant

Volume-depletion side-effects (thirst, postural dizziness, hypotension, dehydration)

Common/uncommon (varies with agent)

Caution in frail/elderly. Consider measuring blood pressure in the lying and standing positions in those at risk of a fall and in those on diuretics

Frequency categories: very common: ≥1/10; common: <1/10 to ≥1/100; uncommon: <1/100 to ≥1/1000; Rare: <1/1000 to ≥1/10,000

Table 4: Uncommon but serious adverse reactions with SGLT2is34–38,54,55
Adverse reactionFrequencyNotes

DKA

Event rate <1/1000 in SPC (between 0 and 2 additional events/1000 person-years in RCTs); real-life events may be higher

  • Inform and advise patients and healthcare professionals about how to prevent, diagnose, and treat DKA

Amputation

Event rate <1/100 in SPC (between 0 and 3 additional events/1000 person-years in RCTs)[A]; real-life events may be lower

  • Encourage routine preventative foot care; regular foot checking
  • Advise patients to report wounds, discoloration, or tender and painful feet
  • Consider stopping therapy if significant foot problems arise, such as infection or skin ulcers

[A] Note: Excess amputations were only seen with canagliflozin in the CANVAS study.4 Subsequent studies with the same SGLT2i and others have not confirmed a significant increase. Any risk is likely to be very low.

Necrotising fasciitis (Fournier’s gangrene): post-marketing reports have been reported (six yellow card reports in >500,000 patient–years. Recent meta-analysis of clinical trials find the association uncertain.56 Patients should be advised to seek urgent medical attention if they experience fever/malaise along with pain, tenderness, or redness in the genital or perineal area.34,57

SGLT2i=sodium–glucose co-transporter-2 inhibitor; DKA=diabetic ketoacidosis; SPC=Summary of Product Characteristics; RCT=randomised controlled trial

Second-line medications that can improve CV and renal outcomes in people with type 2 diabetes

Second-line therapies for diabetes can be selected for their cardiorenal benefits irrespective of HbA1c.20,21 These medications can also be selected when metformin is either inappropriate or insufficient to keep HbA1c below the agreed individualised target (usually 48 mmol/mol for monotherapy, 58 mmol/mol for dual therapy, or higher for people who are frail or have DKD [58–68 mmol/mol for CKD stage 3–4 and CKD stage 5 on dialysis]).58

In general, all people will benefit from an SGLT2i as a second-line therapy, except when it is inappropriate (for example, the patient has a history of DKA, foot problems, or fractures) or when there is a more appropriate drug in a particular situation (for example, GLP-1 analogues in stroke risk). The other option is a GLP-1 RA with proven CV and renal benefits, except when it is inappropriate (for example, in patients with pancreatitis, severe retinopathy, or biliary issues). If neither is appropriate, consider:20,21

  • pioglitazone, except when inappropriate because the patient has fractures, macular oedema, or heart failure
  • a DPP-4i, except when inappropriate because the patient has pancreatitis, biliary issues, or heart failure in the case of saxagliptin
  • a sulfonylurea (SU), except when inappropriate because of hypoglycaemia risk
  • insulin, except when inappropriate because of high hypoglycaemia risk.

Other factors to consider include patient preference for injectable or oral therapy, and current licensing restrictions in relation to GFR. See Table 5 for specific cautions to consider when choosing a second-line therapy.

Table 5: How to choose a second-line medication34
Scenario (presence of risk)SGLT2iGLP-1 RAPioglitazoneDPP-4iSUInsulin

CAD

           

DKD

1, 14

 

14

 

13

13

Heart failure

 

16

2,15

3,16

 

15

Foot disease with vascular complications or sepsis

9

         

Stroke or TIA

           

History of DKA

           

Pancreatitis

 

4

       

Osteoporotic fracture

5

 

6

     

Overweight

           

Hypoglycaemia risk

           

Retinopathy

 

7

8

     

Symptomatic hyperglycaemia

           

Cost

           

Bladder health

10

 

11

     

Biliary health

 

12

       

Key: green=preferred option for second-line medication; yellow=specific cautions apply; red=not the preferred option

The following numbers indicate the specific cautions that should be taken into account when choosing a therapy:59

  1. check the latest SPC for the eGFR advice for the particular SGLT2i35–38
  2. an absolute contraindication in people with established heart failure or those with a raised brain natriuretic peptide level
  3. saxagliptin is an absolute contraindication in people with established heart failure
  4. an absolute contraindication in previously documented pancreatitis, and a relative contraindication in those at high risk of pancreatitis (for example, patients with raised triglycerides, undergoing steroid therapy, on other drugs associated with pancreatitis, or with documented alcoholism)
  5. a relative contraindication in people with established osteoporotic fracture
  6. an absolute contraindication in people who have had a previous osteoporotic fracture, and a relative contraindication in those with post-menopausal osteoporosis or neuropathy
  7. avoid semaglutide
  8. an absolute contraindication in diabetic maculopathy
  9. an absolute contraindication if a person has active diabetic foot disease with vascular complications or sepsis
  10. all medications in this class are relatively contraindicated in people with documented neuropathic bladder and recurrent urinary infections
  11. pioglitazone is relatively contraindicated in previous or active bladder cancer or in non-investigated macroscopic haematuria
  12. a relative contraindication if a person has active gall bladder disease
  13. risk of hypoglycaemia with the combination of insulin and an SU in people with more advanced CKD (stages 4–5)
  14. risk of fractures with the combination of an SGLT2i and pioglitazone in people with evident metabolic bone disease
  15. the combination of insulin and pioglitazone in people with documented fluid retention and/or a high risk of (or established) cardiac failure is a relative contraindication
  16. a lack of clinical benefit with the combination of a DPP-4i and a GLP-1 analogue.

SGLT2i=sodium–glucose co-transporter-2 inhibitor; GLP-1 RA=glucagon-like peptide-1 receptor agonist; DPP-4i=dipeptidyl peptidase-4 inhibitor; SU=sulfonylurea; CAD=coronary artery disease; DKD=diabetic kidney disease; TIA=transient ischaemic attack; DKA=diabetic ketoacidosis; SPC=Summary of Product Characteristics; eGFR=estimated glomerular filtration rate; CKD=chronic kidney disease; GLP-1=glucagon-like peptide-1

What should the prescriber know or do when starting SGLT2i therapy?

When initiating SGLT2i treatment in a patient with type 2 diabetes, the prescriber should:34

  • document the completion of the education session with the person with diabetes
  • advise who can be contacted if the person taking SGLT2i is not feeling well
  • consider reducing the dose of any other glucose-lowering medications, such as insulin and SUs
  • consider the risk of DKA if insulin requirement reduces considerably
  • review diuretics and anti-hypertensive therapy, especially in elderly individuals at risk of dehydration or postural hypotension.

DKA essentials for primary care healthcare professionals

Check blood ketones in people who are taking an SGLT2i and not feeling well. Metabolic decompensation may progress from ketonuria to ketosis and finally to ketoacidosis, requiring urgent treatment to prevent mortality. Blood ketone testing may only be possible at the nearest hospital because most people with type 2 diabetes and most surgeries will not have a ketone meter. If blood ketones are greater than 1.5 mmol/l or if the blood ketones measurement is unavailable, venous blood gases may need to be checked to confirm DKA.60 Once diagnosed, treat DKA according to the Joint British Diabetes Society guidelines60 or a locally adapted protocol. Glucose as well as insulin may be needed for SGLT2i-induced euglycaemic DKA.60

How can you encourage your patients on SGLT2is to reduce their risk of DKA?

To reduce their risk of DKA, patients taking an SGLT2i should be encouraged to:

  • avoid known precipitating factors for DKA, such as starvation or alcohol abuse61
  • at times when oral intake is poor, ensure hydration and, if taking insulin, take half of the normal dose of insulin. Stop taking SGLT2is when feeling unwell and unable to eat and drink51
  • check for ketones (blood ketones are preferable to urine ketones) and seek help with symptoms suggestive of DKA (vomiting, abdominal pain, drowsiness, fatigue, and hyperventilation)51
  • stop taking an SGLT2i 24 hours before elective surgery requiring starvation and restart 24–48 hours after normal oral intake—which may take 1–2 weeks—or follow the advice from the healthcare professionals.34,51,61 More information is available on the British Cardiovascular Society website (bit.ly/3eB0bhr).24

When to stop and restart SGLT2is

Sometimes, it may be necessary to stop SGLT2is to reduce the risk of DKA.33,51 After an episode of DKA, SGLT2is should not be restarted at a future time because the episode may reflect poor beta cell reserve.61

Suspend SGLT2is in the following circumstances:51

  • acute medical admission with severe illness, including COVID-19
  • admission for elective surgery or a procedure requiring starvation
  • vomiting
  • dehydration
  • acute diabetic foot problems.

Restart only after the patient is back to normal and eating and drinking.62 Alternative glucose-lowering therapy may be needed during this period of interruption.

Suggested approaches to implementing best practice

Uptake of the 2021 CaReMeUK Partnership consensus guidance on the management of diabetes, CVD, and renal disease will be assisted by:

  • local champions and enthusiasts
  • involvement of pharmacists
  • presentations to CCGs/stakeholders
  • support from national professional bodies
  • action at all contact—an approach recommended by a best practice guide developed through the British Cardiovascular Society by a CaReMeUK team is that patients should be identified and considered for a therapy review at any relevant clinical contact, whether in primary or secondary care33
  • local agreement on who will initiate treatment with these medications
  • leaflets and resources for both healthcare professionals who are not specialists in diabetes and for people with diabetes33,51
  • dedicated cardiometabolic clinics run jointly by specialists in diabetes, cardiology, and renal medicine.

Summary

Management of people with multiple co-morbidities including diabetes and cardiovascular diseases has transformed in recent times. Clinical trials and international guidelines suggest earlier use of SGLT2is and GLP-1 RAs with proven evidence in the treatment algorithms to improve cardiovascular and renal outcomes in eligible people. Comprehensive education and appropriate use of these medications at all possible patient contacts can make a considerable difference to the health outcomes of our population.

Dr Umesh Dashora, Professor Stephen B Wheatcroft, Dr Peter Winocour, Dr Jim Moore, Professor Ahmet Fuat, Professor Ketan Dhatariya, and Dr Dipesh Patel on behalf of the CaReMeUK Partnership

Want to learn more about this guideline?

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Read the related Guidelines summary

Implementation actions for STPs and ICSs

written by Dr David Jenner, GP, Cullompton, Devon

The following implementation actions are designed to support STPs and ICSs with the challenges involved in implementing new guidance at a system level. Our aim is to help you consider how to deliver improvements to healthcare within the available resources. 

  • Convene a local multidisciplinary working party to review local care pathways and formulary choices for diabetic care
  • Understand that current NICE guidance has not been adapted to meet the new evidence and licensed indications of newer treatments
  • Identify and prioritise anti-diabetic medications with health outcome benefits rather than just glycaemic benefits in local formularies (with specific reference to SGLT2is and GLP-1 RAs)
  • Publish any new adaptations to local formularies, and plan education events to support these and explain the changes and benefits of using the new guidelines
  • Budget for the increased cost of using some of these newer antidiabetic agents and ensure that funds are available to support their use.

STP=sustainability and transformation partnership; ICS=integrated care system; SGLT2i=sodium–glucose co-transporter-2 inhibitor; GLP-1 RA=glucagon-like peptide-1 receptor agonist

References

  1. Hirst J, Ordóñez Mena J, O’Callaghan C et al. Prevalence and factors associated with multimorbidity among primary care patients with decreased renal function. PLOS ONE 2021; 16 (1): e0245131.
  2. Coles B, Zaccardi F, Hvid C et al. Cardiovascular events and mortality in people with type 2 diabetes and multimorbidity: a real‐world study of patients followed for up to 19 years. Diabetes Obes Metab 2021; 23 (1): 218–227.
  3. Ling J, Koye D, Buizen L et al. Temporal trends in co‐morbidities and cardiometabolic risk factors at the time of type 2 diabetes diagnosis in the UK. Diabetes Obes Metab 2021; doi: www.doi.org/10.1111/dom.14323
  4. Neal B, Perkovic V, Mahaffey K et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017; 377 (7): 644–657.
  5. Wiviott S, Raz I, Bonaca M et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 2019; 380 (4): 347–357.
  6. Zinman B, Wanner C, Lachin J et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373 (22): 2117–2128.
  7. Zelniker T, Wiviott S, Raz I et al. SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet 2019; 393 (10166): 31–39.
  8. Cannon C, Pratley R, Dagogo-Jack S et al. Cardiovascular outcomes with ertugliflozin in type 2 diabetes. N Engl J Med 2020; 383 (15): 1425–1435.
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