Total dissent among Brits on how to treat T2D

the “British Medical Journal” has just published the new British recommendations of the National Institute for Excellence in Health and Nursing (Nice) on the drug management of hyperglycemia in type 2 diabetes.

Regarding glycemic goals, it is suggested to aim for an HbA1c level of 7% and not to intensify treatment until it is above 7.5%.

Metformin remains the recommended first-line therapy.

Depending on the cardiovascular risk

Then it all depends on the calculated cardiovascular risk (CV), the UK’s Qrisk 2 (a 10-year morbidity and mortality index believed to be more accurate than score 2). The authors recommend the systematic addition of an SGLT2 inhibitor to metformin in all of these situations: if the Qrisk 2 is greater than 10% (considered a high risk), if at least one cardiovascular risk factor is present before the age of 40 (tobacco, obesity , dyslipidaemia) or cardiovascular or renal disease (microalbuminuria > 30 mg/mmol).

Then the other treatments are proposed according to HbA1c and taking into account other determining factors: either iDPP4 or sulfonamides (or even glitazones, not available in France).

GLP-1 agonists are being withdrawn and only recommended in the 3rd line. They are only preferred to insulin if the patient is overweight and at the request of the patient.

A step-by-step introduction

As with iSGLT2, their introduction should follow metformin rather than immediately to ensure that metformin is well tolerated. Then their prescription must be made after an assessment of the various possible side effects: naturally infectious and, in particular, ketoacidosis. There is an increased risk if there is a history of ketoacidosis, deterioration in the patient’s general condition, severe intercurrent illnesses and a very low-carbohydrate (<10%) and/or ketogenic diet.

Finally, Nice specifies that in CV prevention, aspirin should not be prescribed to a diabetic without proven cardiovascular disease.

Effects that may or may not be transferrable in real life

In fact, Nice proposes making full use of iSGLT2. Above all, it undoubtedly takes into account the excellent quality of the dossier for this class (phase 3 studies and real-life studies). In fact, there are CV benefits in general, in heart failure, in kidney effects, in all patients (including non-diabetics), and these are quantifiable as early as three months after their introduction, all with a very high level of evidence.

They’re also oral medications, so not injectable, which can help with their compliance.

Nice then strongly defends the place of iSGLT2 in microalbuminuria > 30 mg/mmol, proven renal disease, in secondary CV prevention, in high CV risk and heart failure.

How to understand the modest space reserved for arGLP1? Perhaps the length of treatment, injectable, with arGLP1 necessary to produce an effect on the mace (at least three years without interruption) makes its real-life CV advantages more fortuitous, and that Number needed to treat (NNT) quite high, three to six years of treatment? Some commentators make this descent from arGLP1 a decision motivated solely by medico-economic considerations, which are known to be very important to the UK system.

Nice maintains a 3rd line place for arGLP1 by limiting its indications to failure of oral triple therapy in certain T2DM patients with a BMI ≥ 35 kg/m2 or < 35, but as an alternative to insulin or when comorbidities are significant can be reduced weight loss. In summary, the cardiovascular benefits attributed to arGLP1 in the randomized controlled trials are not cited and in no way influence their choice here.

A radical break with the concert of experts and international recommendations, such as the consensus of the American Diabetes Association (ADA) or in France, the French Speaking Diabetes Society (SFD), which place this class very highly in cardiovascular prevention of T2D.

It is difficult to imagine that the Nice experts would deny the arGLP1 these advantages for reasons of economy alone. Furthermore, despite its additional cost, they recommend iSGLT2 because of its CV and kidney effects, which are considered highly significant and clear to all practitioners. Would you doubt the reality of arGLP1’s CV effects in real life? Remember again, these aren’t even mentioned in this update!

Emeritus Professor, University of Grenoble-Alpes

(1) Moran GM, Bakhai C, Song SH, Agwu JC. Policy Committee. Type 2 diabetes: summary of the updated Nice guidelines. BMJ May 18, 2022;377:o775.doi:10.1136/bmj.o775. PM ID: 35584815

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