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Diabetes Distilled: Consider initiating dual glucose-lowering therapy rather than using a stepwise approach in early type 2 diabetes

Pam Brown
A new position statement from Primary Care Diabetes Europe distils out what primary care teams need to know to prescribe glucose-lowering drugs safely and appropriately, so as to optimise care for the people with type 2 diabetes they support. The advice stratifies people with diabetes according to high or very high risk of cardiovascular disease, and recommends that the latter consider starting both metformin and an SGLT2 inhibitor/GLP-1 receptor agonist with cardiovascular benefit immediately rather than in the usual stepwise way, to gain an early additional reduction in cardiovascular events, including heart failure. Treatment recommendations are individualised for those with dominant comorbidities of atherosclerotic cardiovascular disease, heart failure, CKD and obesity, and for frail/elderly people.

The 2020 Primary Care Diabetes Europe (PCDE) position statement, A disease state approach to the pharmacological management of type 2 diabetes in primary care, recommends consideration of initiating both metformin and an SGLT2 inhibitor/GLP-1 receptor agonist with cardiovascular benefit in those at very high risk of cardiovascular disease (CVD), rather than usual UK practice of initiating drugs in a stepwise manner, beginning with metformin and with an interval of 3–6 months to evaluate glycaemic control before adding the second therapy.

In those with chronic kidney disease (CKD), the PCDE guidance recommends using SGLT2 inhibitors provided that eGFR is >45 mL/min/1.73 m2, even when HbA1c is well controlled by metformin alone, although current UK licenses state that SGLT2 inhibitors should not be initiated at eGFR <60. If eGFR drops below 45, teams are encouraged to reduce the dose of glinides and reduce or stop sulfonylureas. In frail/elderly people, metformin is recommended as first-line therapy, followed by DPP-4 inhibitor therapy if individualised glycaemic targets are not met. The statement provides enough background information to aid understanding of the benefits of early diagnosis and tight control in preventing complications, and of the underlying reasons why CVD is so prevalent in those with type 2 diabetes. The stratification into those with very high cardiovascular risk (history of CVD; multiple uncontrolled CVD risk factors, including hypertension, hyperlipidaemia, smoking and/or physical inactivity; eGFR <60 mL/min/1.73 m2; albuminuria; age <40 years at diagnosis) and high CV risk (which includes the remainder of our population with type 2 diabetes) informs early drug choice. In the former patient group, drugs which have demonstrated specific cardiovascular benefits over and above their glucose-lowering effect should be considered immediately alongside metformin.

The PCDE recognises the complexity of the prescribing discussions which primary care teams must have with people with type 2 diabetes, and has brought together in a single document all the resources required to facilitate such discussions. This position statement, based on the most up-to-date evidence, including the ADA/EASD glycaemic management consensus and its 2019 update, offers a simple, patient-centred, clinical decision-making model to assist with day-to-day diabetes therapy conversations. A useful infographic summarises how to stratify and manage cardiovascular risk in those with type 2 diabetes, and two tables summarise the modes of action, adverse effects and prescribing tips for each class of glucose-lowering drugs and the results of the cardiovascular outcome trials. Bulleted boxes pick out treatment recommendations for those with type 2 diabetes and dominant comorbidities of atherosclerotic CVD, heart failure, CKD, and obesity, and for frail/elderly people.

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