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Early initiation of SGLT2 inhibitors: practicalities and pitfalls

Early initiation of SGLT2 inhibitors: practicalities and pitfalls

In our new series showcasing the best of our Pulse Live events, Dr Kevin Fernando summarises the key points from his presentation on SGLT2 inhibitors from London earlier this year

NICE T2 diabetes guidelines

The NICE NG28 type 2 diabetes in adults: management guideline, updated in June 2022, introduced significant practice-changing recommendations for all healthcare professionals working in primary care.

This guideline encourages us to think beyond glycaemia when managing the person living with type 2 diabetes and look for the presence of significant co-morbidities such as atherosclerotic cardiovascular disease, chronic heart failure or chronic kidney disease.  This has been driven by recently published seminal cardiovascular outcome trials for the SGLT2 inhibitor class of medication. These trials demonstrated significant reductions in major adverse cardiovascular events, hospitalisation for heart failure and major adverse renal events. These benefits seem independent of the glucose-lowering properties of the class.

Good glucose control remains important and protects against the microvascular complications of type 2 diabetes (such as retinopathy and neuropathy), but only has a modest impact on the macrovascular complications such as atherosclerotic cardiovascular disease and cerebrovascular disease.

When managing a person living with type 2 diabetes, assess HbA1c, cardiovascular risk (using the QRISK3 calculator and kidney function (both eGFR or creatinine and urinary ACR).

If there is a background of chronic heart failure or established atherosclerotic cardiovascular disease, we should reinforce lifestyle interventions, offer metformin and as soon as metformin tolerability is confirmed (even just a couple of weeks later), we should offer an SGLT2 inhibitor with proven cardiovascular benefit such as canagliflozin, dapagliflozin or empagliflozin.

If the person living with type 2 diabetes is at increased risk of cardiovascular disease with a QRISK3 score of ≥10%, we should do the same: offer metformin and as soon as metformin tolerability is confirmed, offer an SGLT2 inhibitor with proven cardiovascular benefit.

If people experience significant gastrointestinal disturbance with metformin, NICE advises switching to modified release metformin.

NICE CKD guidelines

The NICE NG203 chronic kidney disease: assessment and management guideline was also recently updated and introduced some practice-changing recommendations for primary care.  This guideline reminded us that chronic kidney disease is an independent cardiovascular risk factor and most people with chronic kidney disease die of a cardiovascular event, rather than end-stage kidney disease.

Check urinary ACR, creatinine or eGFR and blood pressure at least annually in all people living with type 2 diabetes.  If urinary ACR rises above 3mg/mmol, this is clinically meaningful proteinuria.  In this situation, offer an ACE inhibitor or ARB and titrate up to the maximally tolerated dose.

If urinary ACR remains ≥30mg/mmol, offer an SGLT2 inhibitor licensed for diabetic kidney disease (currently canagliflozin or dapagliflozin) and consider introducing an SGLT2 inhibitor if urinary ACR persists between 3-30 mg/mmol.

As you can see, we are going to be using SGLT2 inhibitors in a much wider range of clinical scenarios, in people with and without type 2 diabetes. Certain SGLT2 inhibitors are now licensed for the management of heart failure in people without type 2 diabetes (dapagliflozin & empagliflozin) and the management of chronic kidney disease in people without type 2 diabetes (dapagliflozin).

I created a resource to summarise the extra-glycaemic indications of SGLT2 inhibitors.

No drug is without harm, and we must balance the compelling benefits of SGLT2 inhibitors against potential adverse effects.  The commonest adverse effects encountered with SGLT2 inhibitors are mycotic genital infections due to the to their mode of action and ensuing glycosuria.  It is important to reinforce adequate hydration and good personal hygiene to mitigate these adverse effects.

MHRA drug safety advice

The MHRA also reminds in a drug safety update that there is a rare association between SGLT2 inhibitors and diabetic ketoacidosis.  Moreover, this diabetic ketoacidosis can sometimes be euglycaemic i.e., blood glucose levels are normal or near normal.  Warn people taking SGLT2 inhibitors about the signs and symptoms of diabetic ketoacidosis, such as thirst and urinating more than usual, and ask them to seek assessment if they are significant unwell while taking a SGLT2 inhibitor.  If you suspect diabetic ketoacidosis, test for ketones (ideally blood ketones) even if blood glucose levels are normal.  However, there is no need to issue ketone testing strips to those on SGLT2 inhibitors. 

Discuss sick day guidance with people taking SGLT2 inhibitors and advise them to temporarily pause their therapy during any acute significant dehydrating illness. Remind them to restart their therapy once eating and drinking normally and recovered from their illness.

Finally, the MHRA published a further drug safety update regarding reports of Fournier’s gangrene with SGLT2 inhibitors. 

This is incredibly rare. Reassuringly, there was no significant increase in cases of Fournier’s gangrene seen in all major SGLT2 inhibitor trials to date.  Moreover, type 2 diabetes itself is a risk factor for Fournier’s gangrene so is a confounder.  People taking SGLT2 inhibitors should be advised to seek urgent medical attention if they experience severe pain, tenderness, erythema or swelling in the genital or perineal area accompanied by fever or malaise. 

A paper I co-authored provides an SGLT2 inhibitor prescribing tool for type 2 diabetes and other prescribing considerations.

We are in a new era of managing type 2 diabetes in primary care. We need to think beyond glycaemia and look for the presence of significant co-morbidities such as chronic heart failure, atherosclerotic cardiovascular disease and chronic kidney disease. We can use the presence of these co-morbidities to drive choice of therapy, independent of HbA1c.

Dr Kevin Fernando is a GP partner at North Berwick Health Centre. If you want to hear more from Dr Fernando, he is speaking at Pulse Live Birmingham on 6 June 2023. You can register here

Pulse 365 LIVE Events cover a broad array of topics pertinent to you, your patients, and your practice. You will gain free CPD and be able to take part in live Q&As. Specifically created for all practising, GMC-registered GPs and trainees, you will hear from experts across primary and secondary care, and network with like-minded GPs. Sign up for your nearest event today.


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Please note, only GPs are permitted to add comments to articles

Ian Jacobs 25 April, 2023 8:27 am

About time that Type 2 Diabetes was fully recognised as a vascular disease ( at least from the morbidity and deaths that are caused by it ).

Therapeutic approaches to treating T2D in UK have been well behind the curve when considering vascular risk. It was obvious 15-20 years ago that T2D patients should be treated with statins routinely , the use of fibrates was almost a no-no and the favourable effects of glitazones on lipid profiles was usually dismissed ( OK- Romozin s/e’s didn’t do much to promote glitazone usage but Actos did have a role ).

Obviously SGLT2 drugs sound like a real breakthrough.

PS I retired over 10 years ago so admittedly some of the above may be OOD but I still think the points are relevant.
The abandoning of fasting lipid profile tests was a disaster as it emphasised TC and LDL levels and their reductions with statins thus ignoring the important roles of HDL’s and TG’s. A random cholesterol check was vastly inferior as a tool for checking CVD risk and as the test was non- fasting glucose tests were not checked ( a FLP should always have been used as an opportunity to check fasting glucose even in non- diabetics ). OK HbAiC checks do give you a bit more info about post-prandial glucose spikes
but it fails to diagnose a significant proportion of pts with impaired fasting glucose and impaired glucose tolerance – pts who can benefit from lifestyle interventions to delay or even postpone indefinitely the onset of T2D itself.

A very high proportion of T2D’s die from vascular diseases or their complications – atherosclerosis causing CHD, CVD and PVD and increasing the risk of heart failure and renal impairment.