2023-12-15 19:47:28
The Francophone Diabetes Society (SFD) has updated its “Position concerning strategies for the use of anti-hyperglycemic treatments in type 2 diabetes”, the latest version of which dated from 2021. It specifies in particular the place of the most recent molecules which are SGLT2 inhibitors (iSGLT2) and Glucagon-Like Peptide 1 receptor agonists (AR GLP-1), and introduces already that of the double GIP/GLP-1 agonists which should arrive on the market before the next update. Professor Patrice Darmon, diabetologist (AP-HM, La Conception Hospital, Marseille), recalls the main messages.
Univadis: What are the main developments brought by the SFD concerning strategies for the use of anti-hyperglycemic drugs?
Patrice Darmon : We wanted to update therapeutic strategies by refining in this context the positioning of the most recent molecules, namely iSGLT2 and GLP-1 ARs, as well as by specifying the place of double GIP agonists (glucose-dependent insulinotropic polypeptide)/GLP-1: these are not yet available in France but its leader, tirzepatide, will probably be available before our next position. Because we do not yet have evidence of their cardiovascular benefit, they are positioned in algorithms aimed at controlling HbA1c and reducing weight. This year we are offering more precise indications so that practitioners can more easily guide their prescriptions, according to the patient’s profile and always within the framework of the shared medical decision.
Univadis: What are the main recommendations for patients in primary or secondary prevention?
Patrice Darmon : In patients under 75 years of age without atherosclerotic disease, heart failure or chronic kidney disease, when lifestyle modifications and metformin are no longer sufficient, there are three main options: the addition of a dipeptidyl inhibitor peptidase-4 (iDPP4), an iSGLT2 or a GLP-1 AR (or a double agonist in the future). The choice will be guided by several factors such as for example the severity of the glycemic imbalance, that is to say the gap between the current value and the target objective: when the gap is significant, we are more likely to move towards GLP1 ARs and double agonists. The most effective classes for weight loss are, in increasing order of effectiveness, iSGLT2, GLP-1 ARs and especially double agonists. It is also possible to favor GLP1 or iSGLT2 ARs in patients who are at high or very high cardiovascular risk: the level of evidence is lower in primary prevention than in secondary prevention, but they can be valuable when metformin does not not enough. iDPP4 are recommended in frail elderly patients and are an interesting option in patients who have a moderate cardiovascular risk profile: they are drugs that are easy to use and handle without major side effects. In secondary prevention, the recommendations are comparable to those of 2021, namely metformin-iSGLT2 dual therapy from the outset in cases of chronic kidney disease or heart failure, regardless of HbA1c, and metformin-AR GLP-1 dual therapy or metformin-iSGLT2 immediately in case of proven atheromatous disease, once more independently of HbA1c. Finally, the most recent data suggest that GLP1 ARs are more effective in cases of a history of ischemic stroke. In all these patients with cardiovascular or renal disease, the use of metformin-iSGLT2-AR GLP-1 triple therapy is recommended in the event of insufficient effectiveness of dual therapy in reducing HbA1c or if additional reduction is sought. cardiovascular or renal risk, even if the level of evidence is moderate.
Univadis: What are the specificities of treating obese patients?
Patrice Darmon : We have expanded our recommendations by expanding the specific chapter to patients with grade 1 obesity, i.e. people whose body mass index is between 30 and 35 kg/m². This is important when we know that in France, 40% of patients with type 2 diabetes are overweight, and that the same proportion of patients are obese. iSGLT2, but even more so GLP1 ARs and especially double agonists are very effective in weight loss. It was therefore necessary to remember their place in the therapeutic algorithm. Ultimately, triple therapy, metformin-AR GLP1 (or double agonist), iSGLT2 might also be widely used for this category of patients. Our text also allows us to provide elements that echo the evaluation report of the HAS of 2022 on the place of metabolic surgery aimed at achieving remission of diabetes in cases of grade 1 obesity. We are on the same line as this text, but we insist on the caution linked to this surgical approach: it must be considered on a case-by-case basis, if the patient remains unbalanced despite well-conducted care for at least one year, in an expert center and following a multidisciplinary consultation meeting including a diabetologist. We add that the patient must have already received either a GLP1 AR or a double agonist (when they become available), which the HAS report did not include. We consider that these very effective molecules on weight must have been tested before considering metabolic surgery.
Univadis: What precautions should be taken in the elderly?
Patrice Darmon : We must always distinguish between the healthy elderly subject, the frail elderly subject and the dependent elderly subject or one with very poor health. For the first, the decision-making algorithm is comparable to other patients, regardless of their age, even if they must be vigilant regarding the risk of excessive weight loss and sarcopenia with the most recent molecules. When the elderly subject is frail, metformin is the standard treatment, unless it is contraindicated. And it can be associated with an iDPP4 but an iSGLT2 can also be prescribed in cases of heart failure or chronic kidney disease. In these fragile elderly patients, insulin will be more likely to be considered as third line, rather than GLP-1 ARs and double agonists, which expose them to weight loss which can be very harmful in this area. In elderly patients with very poor health, the HbA1c objectives are of course revised upwards, we will use metformin (unless contraindicated), iDPP4 and insulin, discussing the use of an iSGLT2 in the case. per case if there is associated heart failure.
Univadis: Besides the therapeutic strategy itself, what messages are important to remember?
Patrice Darmon : Many elements remain central, such as changes in lifestyle, the place of the patient in the framework of shared medical decision-making, the role of supporting the patient in regular therapeutic re-evaluation in order to fight both once morest inertia and once morest therapeutic piling on, always keeping in mind the question of potential de-escalation when possible. Furthermore, we recall the place of Patient Expert Volunteers from the French Federation of Diabetics, who are specifically trained and can be of great support to patients, just like advanced practice nurses (APNs) or nurses working in the framework of cooperation protocols, very useful for improving the daily monitoring of patients, particularly when they are on insulin therapy. And then we wanted to remind you of the importance of glycemic balance. This seems obvious, and yet: following years where diabetologists were criticized for being too “glucocentric”, the arrival of new cardio- or nephroprotective drugs independently of glycemic balance has put into perspective the importance of achieving glycemic balance. However, this plays a major role in preventing the risk of other complications, particularly retinal or infectious. If it’s obvious, it’s better to say it.
Links of interest: Astra Zeneca, Boehringer Ingelheim, Menarini, Bayer, Novo Nordisk, Lilly, Sanofi, Abbott, MSD, IBSA
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