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SGLT2 inhibitors in type 2 diabetes management

GUIDANCE FROM THE IMPROVING DIABETES STEERING COMMITTEE

Who are the Improving Diabetes Steering Committee?

The Improving Diabetes Steering Committee (IDSC) is a multi-disciplinary group of healthcare professionals assembled to offer evidence-based practical guidance for the use of oral type 2 diabetes medications, particularly focussing on the sodium-glucose cotransporter-2 (SGLT2) inhibitor class in people with type 2 diabetes who have been stratified by cardiovascular disease risk.

The IDSC seeks to support healthcare professionals in appropriate treatment selection for people with type 2 diabetes who are at risk of developing, or have established, cardiovascular disease and examines the role of SGLT2 inhibitor therapy for these people, from the perspective of the current UK treatment pathway.

Learn about SGLT2 inhibitor use in type 2 diabetes management

  • The patient experience of diagnosis and self-management
  • Translating cardiovascular evidence into practice
  • Key evidence and implications for clinical practice

This collection was made possible by educational funding provided by Napp Pharmaceuticals Ltd.

Meet the Improving Diabetes Steering Committee

A benefit/risk tool to inform prescribing decisions for SGLT2 inhibitors

SGLT2 inhibitors can be initiated at any stage of the treatment pathway, however understanding their use in relation to patients at different stages of the treatment pathway and with different comorbidities can be confusing in clinical practice. 

A benefit/risk tool has been developed by the IDSC as a quick reference guide to provide clarity and support clinicians with treatment decisions. The tool uses a traffic light system to help inform clinicians decision making for prescribing SGLT2 inhibitors, and situations where these therapies would not be recommended, with associated evidence levels for each recommendation.

Download the SGLT2 inhibitor prescribing tool

The patient experience of diagnosis and self-management with SGLT2 inhibitors

Management of type 2 diabetes can be complex, and personalising treatment to specific patient needs is becoming more appropriate to help manage this disease. Patient opinions of their goals for diabetes treatments, and thoughts on their current management pathways should be taken into account to optimise treatment outcomes.

Patient and Physician Perspective articles are dual perspective articles that emphasise the patient voice in diabetes management, focusing on aspects such as therapy options and quality of life considerations, giving a voice to these issues.

Read the Patient and Physician Perspective article

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Stay up to date with the latest from Medicine Matters diabetes

Full-text article and summary

SGLT2 inhibitors: Cardiovascular benefits beyond HbA1c—translating evidence into practice

This review builds on the Improving Diabetes Steering Committee 2018 consensus report, which examined the potential role of SGLT2 inhibitors in the management of type 2 diabetes. This article provides practical clinical guidance towards maximising the non-glycemic benefits of SGLT2 inhibitors to reduce adverse cardiovascular outcomes in patients with type 2 diabetes. Read the full-text article here, or scroll horizontally for summary points.

Summary points (1 of 14)

A large proportion of patients with type 2 diabetes have concurrent cardiovascular disease, which is associated with significant morbidity and mortality; therefore, effective management of cardiovascular disease risk in patients with type 2 diabetes is a priority for healthcare systems and affected patients

Ali A et al. Diabetes Ther 2019 10: 1595. doi: 10.1007/s13300-019-0657-8.

Full-text article and summary

SGLT2 inhibitors: Cardiovascular benefits beyond HbA1c—translating evidence into practice

Summary point (2 of 14)

There are multiple overlapping risk factors between type 2 diabetes and cardiovascular disease, including insulin resistance, chronic systemic inflammation, elevated blood pressure, obesity, dyslipidaemia and hypercoagulability.

Ali A et al. Diabetes Ther 2019 10: 1595. doi: 10.1007/s13300-019-0657-8.

Full-text article and summary

SGLT2 inhibitors: Cardiovascular benefits beyond HbA1c—translating evidence into practice

Summary point (3 of 14)

A bidirectional relationship exists between type 2 diabetes and heart failure in terms of disease risk and progression, highlighting the need for effective treatment regimens that recognise both diseases.

Ali A et al. Diabetes Ther 2019 10: 1595. doi: 10.1007/s13300-019-0657-8.

Full-text article and summary

SGLT2 inhibitors: Cardiovascular benefits beyond HbA1c—translating evidence into practice

Summary point (4 of 14)

Although studies have shown the benefits of reducing glycated haemoglobin (HbA1c) on CV outcomes, treatment strategies are needed that address the independent risk factors for cardiovascular disease, in addition to glycaemic control, in patients with type 2 diabetes

Ali A et al. Diabetes Ther 2019 10: 1595. doi: 10.1007/s13300-019-0657-8.

Full-text article and summary

SGLT2 inhibitors: Cardiovascular benefits beyond HbA1c—translating evidence into practice

Summary point (5 of 14)

SGLT2 inhibitors modify many cardiovascular disease risk factors beyond HbA1c, including BP, body weight, hyperinsulinaemia, visceral adiposity, albuminuria, plasma uric acid levels, arterial stiffness and oxidative stress.

Ali A et al. Diabetes Ther 2019 10: 1595. doi: 10.1007/s13300-019-0657-8.

Full-text article and summary

SGLT2 inhibitors: Cardiovascular benefits beyond HbA1c—translating evidence into practice

Summary point (6 of 14)

Proposed mechanisms of action to explain the cardio-protective effects of SGLT2 inhibitors include improved cardiac metabolism and bioenergetics, improved ventricular loading via osmotic diuresis and increased sodium excretion, and inhibition of the sodium/hydrogen exchanger in the myocardium.

Ali A et al. Diabetes Ther 2019 10: 1595. doi: 10.1007/s13300-019-0657-8.

Full-text article and summary

SGLT2 inhibitors: Cardiovascular benefits beyond HbA1c—translating evidence into practice

Summary point (7 of 14)

Randomised cardiovascular outcomes trials of the SGLT2 inhibitors empagliflozin, canagliflozin and dapagliflozin have shown cardiovascular disease or heart failure benefits with these agents in patients with type 2 diabetes at high risk of cardiovascular disease.

Ali A et al. Diabetes Ther 2019 10: 1595. doi: 10.1007/s13300-019-0657-8.

Full-text article and summary

SGLT2 inhibitors: Cardiovascular benefits beyond HbA1c—translating evidence into practice

Summary point (8 of 14)

Three large real-world studies in a total of >1 million patients with type 2 diabetes in routine clinical practice have observed cardiovascular benefits with SGLT2 inhibitors, including reductions in the risk of all-cause mortality and/or hospitalisation for heart failure.

Ali A et al. Diabetes Ther 2019 10: 1595. doi: 10.1007/s13300-019-0657-8.

Full-text article and summary

SGLT2 inhibitors: Cardiovascular benefits beyond HbA1c—translating evidence into practice

Summary point (9 of 14)

Clinical trial data support the benefits of SGLT2 inhibitors in patients with established cardiovascular disease (ie, secondary prevention); however, there is increasing evidence to suggest benefits with SGLT2 inhibitor therapy in patients with cardiovascular disease risk factors but without established cardiovascular disease (ie, primary prevention).

Ali A et al. Diabetes Ther 2019 10: 1595. doi: 10.1007/s13300-019-0657-8.

Full-text article and summary

SGLT2 inhibitors: Cardiovascular benefits beyond HbA1c—translating evidence into practice

Summary point (10 of 14)

The IDSC recommends early initiation of SGLT2 inhibitors in patients with type 2 diabetes and risk factors for cardiovascular disease, regardless of the presence of established cardiovascular disease or heart failure, as this provides an optimal management strategy by decreasing hyperglycaemia, increasing weight loss and lowering systolic blood pressure

Ali A et al. Diabetes Ther 2019 10: 1595. doi: 10.1007/s13300-019-0657-8.

Full-text article and summary

SGLT2 inhibitors: Cardiovascular benefits beyond HbA1c—translating evidence into practice

Summary point (11 of 14)

The National Institute for Health and Care Excellence (NICE) guidelines do not yet provide guidance on the selection of type 2 diabetes treatment according to cardiovascular disease risk; however, the IDSC suggests wider implementation of the American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) consensus report, which recommends considering outcomes beyond glycaemic control (ie, atherosclerotic cardiovascular disease, heart failure, chronic kidney disease, weight management and prevention of hypoglycaemia) when selecting glucose-lowering therapy.

Ali A et al. Diabetes Ther 2019 10: 1595. doi: 10.1007/s13300-019-0657-8.

Full-text article and summary

SGLT2 inhibitors: Cardiovascular benefits beyond HbA1c—translating evidence into practice

Summary point (12 of 14)

There are several challenges to adopting a new treatment approach when managing patients with type 2 diabetes, including a lack of familiarity with newer glucose-lowering agents, a lack of prescribing options through local formularies, and limited flexibility within local guidelines.

Ali A et al. Diabetes Ther 2019 10: 1595. doi: 10.1007/s13300-019-0657-8.

Full-text article and summary

SGLT2 inhibitors: Cardiovascular benefits beyond HbA1c—translating evidence into practice

Summary point (13 of 14)

SGLT2 inhibitor therapy may represent the best option when escalating from metformin therapy in many patients with type 2 diabetes and risk factors for cardiovascular disease, particularly given the outcome benefits beyond attainment of glycaemic targets and the shared risk factors for type 2 diabetes and cardiovascular disease, including elevated BP, dyslipidaemia and obesity.

Ali A et al. Diabetes Ther 2019 10: 1595. doi: 10.1007/s13300-019-0657-8.

Full-text article and summary

SGLT2 inhibitors: Cardiovascular benefits beyond HbA1c—translating evidence into practice

Summary point (14 of 14)

The Improving Diabetes Steering Committee provided recommendations for SGLT2 inhibitor use the following groups of patients with type 2 diabetes:

  • Patients with type 2 diabetes and established cardiovascular disease;
  • patients with type 2 diabetes and a high risk for cardiovascular disease;
  • patients with type 2 diabetes and a lower risk for cardiovascular disease; and 
  • frail patients with type 2 diabetes.

Ali A et al. Diabetes Ther 2019 10: 1595. doi: 10.1007/s13300-019-0657-8.

Full-text article and summary

SGLT2 inhibitors in type 2 diabetes management: Key evidence and implications for clinical practice

This review provides an overview of the current concerns and misconceptions on the use of SGLT2 inhibitors for the treatment of type 2 diabetes and provides an overview of their place within the diabetes management pathway. Read the full-text article here, or scroll horizontally for summary points.

Summary point (1 of 10)

Based on the evidence for SGLT2 inhibitors summarised in the review, the authors developed a benefit/risk tool that can be used as a quick reference for clinicians in routine practice.

Wilding J et al. Diabetes Ther 2018. 9: 1757. doi: 10.1007/s13300-018-0471-8

Full-text article and summary

SGLT2 inhibitors in type 2 diabetes management: Key evidence and implications for clinical practice

Summary point (2 of 10)

SGLT2 inhibitors reduce the reabsorption of glucose in the kidney in an insulin-independent manner, thereby increasing glucose excretion via urine.

Wilding J et al. Diabetes Ther 2018. 9: 1757. doi: 10.1007/s13300-018-0471-8

Full-text article and summary

SGLT2 inhibitors in type 2 diabetes management: Key evidence and implications for clinical practice

Summary point (3 of 10)

Three SGLT2 inhibitors are approved in the UK: canagliflozin, dapagliflozin and empagliflozin. National Institute for Health and Care Excellence (NICE) and Scottish Intercollegiate Guidelines Network (SIGN) guidelines recommend the use of SGLT2 inhibitors for first intensification of type 2 diabetes treatment after metformin failure.

Wilding J et al. Diabetes Ther 2018. 9: 1757. doi: 10.1007/s13300-018-0471-8

Full-text article and summary

SGLT2 inhibitors in type 2 diabetes management: Key evidence and implications for clinical practice

Summary point (4 of 10)

Guidelines also note that SGLT2 inhibitors can be administered in combination with other anti-diabetic drugs, such as insulin and glucagon-like peptide-1 receptor antagonists.

Wilding J et al. Diabetes Ther 2018. 9: 1757. doi: 10.1007/s13300-018-0471-8

Full-text article and summary

SGLT2 inhibitors in type 2 diabetes management: Key evidence and implications for clinical practice

Summary point (5 of 10)

Randomised controlled trials and real-world evidence have shown that SGLT2 inhibitors achieve and maintain glucose levels, are associated with weight loss (reduce visceral fat), and have cardio- and renoprotective effects.

Wilding J et al. Diabetes Ther 2018. 9: 1757. doi: 10.1007/s13300-018-0471-8

Full-text article and summary

SGLT2 inhibitors in type 2 diabetes management: Key evidence and implications for clinical practice

Summary point (6 of 10)

SGLT2 inhibitors are generally well tolerated; however, there are some patient populations that may be at increased risk of adverse events.

Wilding J et al. Diabetes Ther 2018. 9: 1757. doi: 10.1007/s13300-018-0471-8

Full-text article and summary

SGLT2 inhibitors in type 2 diabetes management: Key evidence and implications for clinical practice

Summary point (7 of 10)

Genital infections are a common adverse event with SGLT2 inhibitors. To achieve optimum treatment benefit, education on the risk of these and practical hygiene advice at the start of treatment are recommended.

Wilding J et al. Diabetes Ther 2018. 9: 1757. doi: 10.1007/s13300-018-0471-8

Full-text article and summary

SGLT2 inhibitors in type 2 diabetes management: Key evidence and implications for clinical practice

Summary point (8 of 10)

There is conflicting evidence for the risk of lower limb amputation and bone fractures with SGLT2 inhibitors; however, high-risk individuals should avoid SGLT2 inhibitors. Preventative footcare advice and ongoing monitoring is recommended.

Wilding J et al. Diabetes Ther 2018. 9: 1757. doi: 10.1007/s13300-018-0471-8

Full-text article and summary

SGLT2 inhibitors in type 2 diabetes management: Key evidence and implications for clinical practice

Summary point (9 of 10)

Patients receiving SGLT2 inhibitors may experience diabetic ketoacidosis, although this is rare. Diabetic ketoacidosis monitoring should be implemented when administering SGLT2 inhibitors.

Wilding J et al. Diabetes Ther 2018. 9: 1757. doi: 10.1007/s13300-018-0471-8

Full-text article and summary

SGLT2 inhibitors in type 2 diabetes management: Key evidence and implications for clinical practice

Summary point (10 of 10)

SGLT2 inhibitors should be discontinued immediately in patients with acute illness or planned surgical procedures, but can be resumed following full recovery.

Wilding J et al. Diabetes Ther 2018. 9: 1757. doi: 10.1007/s13300-018-0471-8

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