Dr Samuel Seidu and Professor Kamlesh Khunti discuss the recommendations of the Primary Care Diabetes Europe position statement on the management of type 2 diabetes

SEIDU_Samuel

Dr Samuel Seidu

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Read this article to learn more about:

  • the simplified approach to cardiovascular risk stratification in the Primary Care Diabetes Europe position statement
  • early initiation of effective treatment to prevent worsening of complications
  • pharmacological treatment options for patients with type 2 diabetes and co-morbidities.

Read this article at: GinP.co.uk/455643.article

There are two main imperatives in the primary care management of diabetes. First is the recognition that the person with diabetes receiving treatment in primary care tends to have other multiple long-term conditions, most of which are associated with diabetes or are complications of the disease. Therefore, treating type 2 diabetes is not just about managing blood glucose, but should also focus on managing blood pressure, weight loss, blood lipid levels, psychological factors, and screening for and managing complications including renal problems, retinopathy, foot ulcers, and cardiovascular disease (CVD). Secondly, even though timely treatment of type 2 diabetes is needed to reduce the risk of complications, many patients do not achieve current glycated haemoglobin targets with the available treatment options.1

The PCDE position statement on the management of type 2 diabetes

In June 2020, Primary Care Diabetes Europe (PCDE) published a position statement, A disease state approach to the pharmacological management of type 2 diabetes in primary care.2 The aim of the position statement is to provide a simple and pragmatic tool for primary care clinicians and other healthcare professionals for the pharmacological management of people with type 2 diabetes and co-morbidities.2 It also offers a novel risk stratification approach and practical recommendations to help link patients with the appropriate care and prevent diabetes-associated complications. The position statement is intended to supplement rather than replace established national and international guidelines.

Risk stratification methods described in the position statement

The European Society of Cardiology and European Association for the Study of Diabetes guidelines categorise cardiovascular risk in people with diabetes as very high, high, and moderate.3 These definitions are based on the duration of diabetes and presence of other cardiovascular risk factors. Treatment recommendations are made based on these risk categories. This seems rather complex for front-line GPs. In the 2020 PCDE position statement, risk stratification has been simplified and made easier to apply, while maintaining the evidence base for stratification.

The PCDE guidance assumes that people with diabetes are either at very high risk or high risk. The very high risk classification can be assumed in five patient groups (see Box 1). All other patients with type 2 diabetes are at high risk of CVD and, therefore, aggressive multifactorial control of cardiovascular risk factors and glycaemic control should be considered from the outset.2

Box 1: Patient groups considered to be at very high cardiovascular risk by the PCDE position statement2

The PCDE position statement considers patients in the following five groups to be at very high cardiovascular risk:

  • patients with a history of established CVD, accounting for about one-fifth of people with diabetes in primary care,4 which is widely recognised as an important predictor of future MACE5
  • patients with decreased eGFR, which is a strong independent predictor of MACE in people with type 2 diabetes6
  • patients with albuminuria, which is also a strong independent predictor of MACE in people with type 2 diabetes6
  • patients with multiple cardiovascular risk factors in addition to diabetes, who are at a much higher risk of CVD
  • patients with early-onset type 2 diabetes —there is evidence to suggest that early-onset type 2 diabetes represents an aggressive form of the disease in terms of cardiovascular risk.7

PCDE=Primary Care Diabetes Europe; CVD=cardiovascular disease; MACE=major adverse cardiovascular events; eGFR=estimated glomerular filtration rate

Treatment recommendations

To avoid therapeutic inertia, consider dual therapy at diabetes diagnosis in patients who are likely to benefit from better glycaemic control, to maintain good glycaemic control for as long as possible.2,8–10 The decision as to whether to initiate dual therapy at diagnosis should be based on considerations about individual patient characteristics and treatment goals.

Treatment options should be selected based on the patient’s individual risk factors.

Patients at very high risk of CVD

In patients with atherosclerotic cardiovascular disease (ASCVD), consider initiating metformin and a sodium-glucose co-transporter-2 inhibitor (SGLT2i) or glucagon-like peptide-1 receptor agonist (GLP-1RA), rather than using a stepwise approach. This advice is meant to address the issue of therapeutic inertia in glycaemic control and, at the same time, prevent the recurrence of ASCVD, even if the glycaemic target is met. If, however, this initial combination therapy is not preferred because of issues such as side-effects of medications or cost implications and a stepwise approach is preferred for glycaemic control, then metformin should be used as first-line therapy, with an SGLT2i or GLP-1RA with proven cardiovascular benefit as second-line therapy if further glycaemic control is needed. The use of basal insulin should be considered with caution when other options have failed and glycaemic targets are not met.2

In patients with heart failure (HF), the position statement advocates early consideration of initiating metformin and an SGLT2i rather than a stepwise approach. However, if a stepwise approach is preferred for glycaemic control, then metformin should be used as first-line therapy and an SGLT2i as second-line therapy. Avoidance of pioglitazone and saxagliptin, and caution when prescribing basal insulin are paramount.2

In patients with chronic kidney disease, a combination of metformin and an SGLT2i should be considered rather than a stepwise approach, according to the approved restrictions of dose and indications by estimated glomerular filtration rate (eGFR). Metformin should be used as first-line therapy if eGFR is >30 ml/min/1.73 m2 for glycaemic control. An SGLT2i should be considered as second-line therapy for glycaemic control, even in patients well controlled on metformin alone, especially in those with severe albuminuria, because of its extra-glycaemic renal benefits. A GLP-1RA should be used as third-line therapy or if previous treatments are not tolerated, or a dipeptidyl peptidase-4 inhibitor (DPP-4i) if GLP-1RAs are not tolerated, not available, or not preferred. The position statement advises to reduce the doses of glinides and sulfonylureas (SUs) or discontinue SUs if eGFR is <45 ml/min/1.73 m2 to lower the risk of hypoglycaemia. Prescribing instructions for specific agents should be consulted for dosing instructions based on eGFR.2

Patients at high risk of CVD

In patients at high cardiovascular risk, consider initiating metformin together with an SGLT2i, GLP-1RA, or DPP-4i rather than adopting a stepwise approach.2 However, if a stepwise approach is preferred, then metformin should be used as first-line therapy, and an SGLT2i, GLP-1RA, or DPP-4i as second-line therapy where cost is not prohibitive. Of these, an SGLT2i or GLP-1RA with proven cardiovascular benefit is preferred. Newer-generation SUs or glinides can be considered when drug cost must be minimised. Pioglitazone is preferred in patients with non-alcoholic fatty liver disease and where insulin resistance predominates. Basal insulin should be considered when other therapies have been explored and glycaemic targets have not been met. Full basal–bolus insulin therapy should be used only as a last resort.2

Obese or overweight people with type 2 diabetes

In people who are obese or overweight, consider initiating metformin together with a GLP-1RA or SGLT2i rather than using a stepwise approach. Metformin should be used as first-line therapy, followed by a GLP-1RA or SGLT2i as second-line therapy for glycaemic control. Where possible, avoid treatments that cause weight gain, including most SUs, glinides, pioglitazone, and insulin. If basal insulin is required, consider fixed-ratio insulin/GLP-1RA combinations.2

Elderly frail population

In elderly, frail people, maintaining good glycaemic control to avoid long-term complications is not as much of a priority as maintaining a good quality of life and avoiding acute symptoms of hyperglycaemia and side-effects of medications. Therefore, the recommendation is to avoid stringent glycaemic targets that increase the risk of hypoglycaemia. Metformin is recommended as first-line therapy if tolerated and not contraindicated. DPP-4i is a safe and easy-to-use option.2 It is also important to assess adherence and to avoid multiple daily injectable medications when possible.2

Managing side-effects of treatments

Table 1 details the common side-effects associated with each drug class and provides practical prescribing tips to ameliorate these side-effects. In summary, gastrointestinal side-effects are associated with metformin,11 GLP-1RAs,12 and acarbose.13 In all of these cases, side-effects may be mitigated if the dose is increased slowly. Insulin, SUs, and glinides are associated with hypoglycaemia and weight gain.14 If hypoglycaemia develops, consider reducing the dose or modifying the timing of the injection in the case of insulin. Genitourinary tract infections are a common side-effect of SGLT2is15 and patients should be encouraged to adhere to proper hygiene to avoid genital mycotic infections. Diabetic ketoacidosis is a rare but recognised complication associated with both SGLT2is and GLP-1RAs.15–18 It has been reported in insulin-dependent patients who underwent rapid discontinuation or dose reduction of insulin when starting treatment with these agents. A stepwise approach to insulin reduction and addressing the sick day rules is recommended.19 Pioglitazone is associated with fluid retention, increased weight, and osteoporotic fractures, and should be avoided in people with HF and those prone to osteoporotic fractures.11,20,21

Table 1: Common side-effects and prescribing tips for the use of anti-hyperglycaemic medications in the treatment of type 2 diabetes2
Drug classCommon side-effectsPrescribing tips

Metformin

GI symptoms11

GI symptoms can be limited by gradual dose escalation or dose reduction22

Glinides

Modest weight gain, slight risk of hypoglycaemia23,24

Hypoglycaemia usually occurs due to excessive dosage; use with caution in situations in which hypoglycaemia is most likely to occur14

GLP-1RAs

GI symptoms including nausea, diarrhoea, vomiting, decreased appetite, abdominal pain, constipation.12  Increased risk of acute pancreatitis with some GLP-1RAs12,25,26

Increased risk of diabetic retinopathy was observed with semaglutide in SUSTAIN 6 trial27

Nausea, other GI symptoms and diabetic retinopathy risks can be limited by gradual dose escalation.12 If patients do not tolerate a gradual dose escalation, consider delaying dose escalation by one additional week. It is also recommended to have more frequent and smaller meals to reduce the risk of GI side-effects

Patients are advised to use a different injection site each week to avoid injection site reactions12

SGLT2is

Genitourinary tract infections (with higher risk in women and potential greater impact on quality of life in elderly people),28–30 dehydration, and hypotension from increased urination31

Monitor and treat genitourinary infections as needed

In conditions of reduced oral intake or potential fluid losses such as GI illness, carefully monitor volume status and discontinue treatment until fluid loss is corrected32

Be cautious of other pre-existing factors that could increase fracture risk, such as history of fractures and higher risk of falls33

Encourage proper hygiene in both female and male patients to avoid genital mycotic infections34

DPP-4is

Upper respiratory tract infection, urinary tract infection, nasopharyngitis, and headache35 plus risk of HF in the case of saxagliptin36

Generally safe for most patients

Sulfonylureas

Hypoglycaemia, weight gain37

Hypoglycaemia usually occurs due to excessive dosage; use with caution in situations in which hypoglycaemia is most likely to occur37

Weight gain is usually countered by the concurrent administration of metformin37

Only gliclazide may be used in CKD stage 3 or worse.37,38 For all others, the dose should be reduced in patients with eGFR 60–90 ml/min/1.73 m2. Contraindicated in patients with severe renal impairment (eGFR <60 ml/min/1.73 m2)38

Even in the case of gliclazide, a hypoglycaemic episode occurring in these patients may be prolonged, so appropriate management should be initiated

Acarbose

Flatulence, mild diarrhoea39

Side-effects may be mitigated if the dose is increased slowly

Pioglitazone

Weight gain, swelling, risk of bone fracture, bone loss11,20,21

Should not be used in patients with history of or active bladder cancer40 or those at risk of HF20

Insulin

Hypoglycaemia, weight gain11

If hypoglycaemia develops, consider reducing dose or modifying timing of injection. Patients should be encouraged to rotate injection sites.

GI=gastrointestinal; GLP-1RA=glucagon-like peptide-1 receptor agonist; SGLT2i=sodium-glucose co-transporter-2 inhibitor; DPP-4i=dipeptidyl peptidase-4 inhibitor; HF=heart failure; CKD=chronic kidney disease; eGFR=estimated glomerular filtration rate

Adapted from Seidu S, Cos X, Brunton S et al. A disease state approach to the pharmacological management of Type 2 diabetes in primary care: a position statement by Primary Care Diabetes Europe. Primary Care Diabetes 2020. Epub ahead of print. doi.org/10.1016/j.pcd.2020.05.004 Reproduced with permission

Care of people with diabetes in primary care during the COVID-19 pandemic

In a recent whole-population analysis in England, of the in-hospital COVID-19-related deaths during the study period, 31.4% occurred in people with type 2 diabetes.41 The majority of people with type 2 diabetes are managed in primary care, so primary care teams have a crucial role to play in the prevention of these deaths.41 The usual sick day rules apply to those who are unwell with COVID-19.19 People with urgent complications such as diabetic ketoacidosis should be admitted to hospital as normal, with expedited treatment and discharge to help reduce length of hospital stay.42 Primary care should prioritise services based on individual risk factors and clinical needs.42 Diabetic foot checks are classed as essential services and should continue where staffing levels and protective measures allow.43

Summary

In recent years, the proliferation of new treatment options for type 2 diabetes has necessitated the development of a simple but evidence-based scheme that addresses the challenges faced by patients and their clinical teams in primary care settings. CVD is one of the most prevalent co-morbidities causally associated with type 2 diabetes and is the primary reason for mortality in these patients. Early combination therapy is advocated in this guidance to minimise the risk of CVD and other complications in patients with type 2 diabetes.

Dr Samuel Seidu

GP, Clinical Lead, and Mentor for Diabetes, Leicester

Head of Research, Primary Care Diabetes Europe

NIHR Clinical Lecturer in Primary Care, Diabetes Research Centre, University of Leicester 

Professor Kamlesh Khunti

Professor of Primary Care Diabetes and Vascular Medicine, University of Leicester

Co-Director, Diabetes Research Centre, University of Leicester

Director, UK National Institute for Health Research in Applied Research Collaborations East Midlands

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 with implementing new guidance at a system level. Our aim is to help you consider how to deliver improvements to healthcare within the available resources. 

  • Review local care pathways for type 2 diabetes in the light of the guidance discussed in this article and also NICE guidance
  • Consider whether in view of the COVID-19 pandemic these local care pathways need modification to reduce face-to-face consultations, e.g. regarding choice of drug, the need for blood glucose self-monitoring education
  • Update and publish modified pathways after a multi-professional review, taking the cost of therapies as well as their efficacy into account
  • Define algorithms for the use of anti-diabetic drugs and publish these in the local formulary
  • Encourage a proactive approach to managing diabetes during the COVID-19 pandemic, recognising that this group of patients is at increased risk of COVID-19 mortality as well as cardiovascular events.

STP=sustainability and transformation partnership; ICS=integrated care system

Implementation actions for clinical pharmacists in general practice

written by Gupinder Syan, Training and Clinical Outcomes Manager, Soar Beyond Ltd

The following implementation actions are designed to support clinical pharmacists in general practice with implementing the guidance at a practice level.

Management of co-morbidities associated with type 2 diabetes is increasingly being undertaken by clinical pharmacists as they grow in competence and can start to deal with more complex patients. This is an ideal area for QI for practice pharmacists in primary care, particularly in the context of COVID-19, where many of these co-morbidities may have worsened or have been poorly managed.

Soar Beyond recommends that clinical pharmacists use the simplified 4D™ QI methodology described below when managing patients with type 2 diabetes and co-morbidities.

  • Step 1: Diagnose —identify priorities for management based on clinical risk using searches and audit tools. Tackle one group at a time, based on clinical need within your organisation and your competence:
    • 1. Patients with T2D, HbA1c above target, and ASCVD with:
      • uncontrolled high BP
      • not on a statin/high cholesterol
      • HF
      • overweight/obese
      • diabetic retinopathy
      • smoking risk factor
    • 2. Patients with T2D, HbA1c above target, and CKD with:
      • reduced eGFR
      • high urine ACR or albuminuria
      • diabetic kidney disease or diabetic nephropathy
    • 3. Patients with T2D, HbA1c above target, and frailty with:
      • moderate or severe frailty
      • a risk of hypoglycaemia (including from medication)
    • 4. Patients who have all three risk factors above.
    • Present your findings to the practice, define a clear QI project scope, and seek approval to proceed.
  • Step 2: Design —working with the MDT, generate ideas for resolving issues and appraise the options. Co‑design a plan to make changes that will improve the management of the selected at-risk patient groups.
  • Step 3: Deliver —agree a plan to deliver the changes, including creation of any resources (e.g. templates, alerts) and report back at regular intervals.
  • Step 4: Demonstrate— compare the clinical and process outcomes with the baseline metrics that were agreed in the original project scope. Review benefits and lessons learned.

The i2i Network has a range of training and implementation resources designed to support general practice pharmacists on their development journey for managing type 2 diabetes, covering: core skills at first and second intensification; enhanced skills dealing with implementing QI for patients with co‑morbidities as described above; and injectable therapies. These are available for free to clinical pharmacists through non-promotional funding by selected pharmaceutical industry partners.

QI=quality improvement; T2D=type 2 diabetes; HbA1c=glycated haemoglobin; ASCVD=atherosclerotic cardiovascular disease; BP=blood pressure; HF=heart failure; CKD=chronic kidney disease; eGFR=estimated glomerular filtration rate; ACR=albumin to creatinine ratio; MDT=multidisciplinary team

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