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SGLT2 inhibitors - benefits for the pump, pipes and filter

Dr Rob Walker - 30 Jul, 2020

As we start progressing to the ‘new normal’ in General Practice (hands up like me who is less than enthusiastic about that term - what, on earth, is normal about what are doing currently?!) one of the areas I know all our practices will be busy looking at is our patients with diabetes. After a 4-5 month hiatus in reviewing our chronic disease registers, we are all too aware of the potential harm our diabetic population may be exposed to if we don’t start reviewing their glycaemic control and CVD risk factors. The risks patients with diabetes (especially if poorly controlled) are exposed to has been sharply brought into focus with their excess complication rate from COVID-19. So I’m sure your brilliant nurses and admin staff will be ferreting through high HbA1c results, overdue checks, and getting patients like Jim in for their reviews. 

Obviously, really focusing on lifestyle changes, weight loss, etc. is of paramount importance for Jim, but what pharmacological agents should we be using for hyperglycaemia in type 2 diabetes? It used to be so much more straight forward…metformin +/- a sulphonylurea, and if you’re not winning insulin. The thiazolidinediones made a bid for their place on the rostrum in the early 2000s but then CVD safety concerns over rosiglitazone put a large dampener on that. However, since about 2010 we have had 3 new kids on the block that have really come into regular use in primary care - the GLP1 agonists (the ‘tides’), DPP4 inhibitors (the ‘gliptins’) and the SGLT2 inhibitors (the ‘flozins’), which has been fantastic to give our patients more choice and options, but has made our life even more complicated! 

Most interest in the last few years has centred around the SGLT2 inhibitors. I’m sure many of us were a little wary of these drugs when they first started making their way into primary care, especially if like me you are not an ‘early adopter’ of either medicines (or technology..). When concerns were being raised over lower limb amputations, even in tightly controlled RCTs, as well as euglycaemic DKA, I was not rushing to prescribe them - it just felt like we may be heading to another rosiglitazone story. But my fears have been substantially allayed - yes there are (very rare) risks of lower limb amputations and euglycaemic DKA, but we now have convincing evidence that they improve CVD outcomes, especially for people with known IHD, they reduce heart failure risk and have increasingly been shown to improve renal outcomes. The CREDENCE trial published a year ago, recruited patients with type 2 diabetes and albuminuric CKD and was stopped early after just over 2 and a half years, due to significant improvements in the canagliflozin group vs placebo, with a 30% lower risk of the primary outcome (a composite of dialysis, transplant, sustained eGFR <15, doubling of serum creatinine and death from renal or CVD causes). What about the absolute risk improvement I hear you cry? Well, that was pretty impressive too with a NNT of only 28 over 2.5 years to prevent a combined renal outcome (end-stage kidney disease, doubling of serum creatinine or renal death). Importantly many of the patients had low eGFRs down to 30. In June 2020 this led to the European Commission granting a change in the license for canagliflozin (for the lower 100mg dose) to be initiated in CKD with eGFRs ≥30. Currently in the UK licensing restrictions remain that we can only initiate canagliflozin (and all SGLT2 inhibitors) with eGFR ≥60, but it is highly likely the UK will follow suit and relax prescribing guidelines for lower eGFRs, but in the meantime, we should still consider SGLT2 inhibitors for patients with albuminuria and eGFR ≥60. 

So, as a good NEJM editorial concluded 18 months ago, the SGLT2 inhibitors have in-creasing evidence now to support benefits for the ‘pump’ (heart failure), the ‘pipes’ (vascular disease) and the ‘filter’ (kidneys). There is no such thing as a drug for everyone, but the SGLT2 inhibitors are increasingly looking like a second-line option, after metformin, for many people with type 2 diabetes, including someone like Jim. 

We have updated all of our diabetes material ready for our Autumn/Winter LIVE webinar series, so if you need a brush up of your diabetes management why not join us then? Or if you need some more in-depth diabetes training why not join us for our bespoke LIVE diabetes webinar on Thursday 3rd December? We look forward to seeing you then!

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