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The use of GLP-1 receptor agonists and iSGLT2 is becoming increasingly common, in line with new guidelines issued by the learned societies of cardiology, nephrology and diabetology. However, the enthusiasm aroused by these new drugs needs to be tempered and their use in the very elderly and/or frail needs to be carefully considered by the lack of scientific studies in this population category, , and their prescription requires a comprehensive geriatric assessment before initiating this type of treatment., Competing Interests: les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Incretin gut hormones, especially glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), raise a huge interest in diabetology. GLP-1 receptor agonists have gained a privileged role in the management of type 2 diabetes (T2D). They improve glucose control without inducing hypoglycaemia, while promoting weight loss. Furthermore, they protect people with T2D against atherosclerotic cardiovascular disease and contribute to reduce the risk of heart failure and chronic kidney disease, two other common complications of T2D. A recent innovation consists in the development of co-agonists that target both GIP and GLP-1 receptors. Whereas the co-infusion of GIP and GLP-1 failed to further reduce hyperglycaemia of T2D compared to GLP-1 single infusion, tirzepatide, an original dual unimolecular biaised GIP/GLP-1 agonist, showed a remarkable improvement of glucose control in the SURPASS programme in patients with T2D. Consequently, it is now commercialized in many countries for the management of T2D. GLP-1/glucagon (GCG) co-agonists and GIP/GLP-1/GCG poly-agonists are currently in development, aiming to benefit from the favourable effects of GCG on energy expenditure and liver lipid metabolism, while mitigating the hyperglycaemic effects of this hormone thanks to balanced effects of GLP-1 and/or GIP. They might occupy in the future an interesting place in the management of obesity and its metabolic complications among which T2D and liver steatosis.

In addition to optimal glycemic control and management of other factors aggravating the pathology (hypertension, dyslipidemia, -obesity), the cornerstone of treatment of diabetic kidney disease (DKD) includes blockers of the renin-angiotensin system, sodium-glucose cotransporter 2 inhibitors or nonsteroidal antagonists of the mineralocorticoid receptor (finerenone). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are recommended in the treatment of high-risk patients with type 2 diabetes (T2DM) to reduce cardiovascular (CV) risk. Data from CV studies indicate a nephroprotective effect of certain GLP-1 RAs in T2DM patients with DKD. The FLOW study published in May 2024, analyzing the impact of semaglutide vs placebo on renal events as primary outcome, confirms this renal protection of GLP-1 RAs., Competing Interests: N. Paquot est coinvestigateur principal pour le CHU de Liège dans l’essai SURPASS-CVOT et déclare avoir reçu des honoraires comme orateur et/ou membre d’un conseil scientifique de la part des firmes AstraZeneca, Boehringer Ingelheim, Lilly, NovoNordisk, Fresenius et Sanofi.

Both glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) improve cardiorenal -prognosis of at-risk patients with type 2 diabetes thanks to pleiotropic effects that are either common or specific. This article discusses the clinical efficacy of a combined therapy with the two medications. Data were obtained from post hoc analyses of subgroups of participants to cardiovascular outcome trials and from real-life observational retro-spective cohort studies. The reported superiority of the combination versus either monotherapy should be confirmed in an ongoing large prospective trial (PRECIDENTD). The extra-cost of such a combined therapy as well as the common underuse of each pharmacological class in daily clinical practice deserve attention., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Patients with type 2 diabetes (T2D) are frequently exposed to comorbidities, mainly cardiovascular complications. Thus, a polypharmacy is often mandatory, targeting not only T2D but also comorbidities such as coronary artery disease and heart failure. Interestingly, some drugs improve glucose control, cardiovascular prognosis and heart failure outcome. This versatility may cause trouble regarding prescriptions by practitioners, especially because of the restricted conditions for the reimbursement in Belgium. This clinical vignette aims at discussing the path of pharmacotherapy for a patient with T2D who suffers from a myocardial infarction and subsequently develops a heart failure. It will mainly focus on the place of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporters 2 (gliflozins) as well as the potential of their combination in this context, considering the current restrictions for the reimbursement.

The management of obesity is changing dramatically with the emergence of new drug treatments. Glucagon-like peptide-1 (GLP-1) receptor agonists are approved for this indication in Switzerland, and approval is currently being sought for a GLP-1 and glucose-dependent insulinotropic polypetide (GIP) co-agonist. Reimbursement conditions are restrictive, and patients are given only one opportunity to achieve the weight loss required for continued reimbursement. The popularity of these treatments has led to worldwide stock-outs for several months now, and it is essential that prescribers respect the indications so as not to prejudice obese patients. This article provides a review of the treatments available and the conditions under which they are reimbursed, as well as those that should be reimbursed soon., Competing Interests: L’auteure ne déclare aucun conflit d’intérêts en relation avec cet article.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) reduce the risk of cardiovascular (CV) complications in patients with type 2 diabetes (T2DM) and atherosclerotic cardiovascular disease (ASCVD) in placebo-controlled CV outcome trials. This article compares the proportion of T2DM patients treated with GLP-1RAs in retrospective observational studies that recruited T2DM patients with versus without established ASCVD. Nine cohorts from seven studies were collected in the international literature between 2019 and 2022. Overall, the percentages of patients treated with GLP-1RAs were low (< 10 %) in most studies. Surprisingly, the use of GLP-1RAs in patients with ASCVD was slightly lower in 7 out of 9 cohorts when compared to the use in patients without ASCVD (odds ratio 0.80, 95% CI 0.79-0.81). Despite a positive trend over the last decade, the real-world use of GLP-1RAs remains limited, especially in patients with established ASCVD. The reasons for this underuse are diverse. Bridging the gap between clinical evidence of cardioprotective effects of GLP-1RAs and their underuse in clinical practice in T2DM patients at high/very high CV risk, more particularly those with established ASCVD, should be considered as a key objective for health care providers, especially cardiologists.

Both physicians and patients dream of an efficacious and safe pharmacological approach to treat obesity. Unfortunately, most anti-obesity drugs prescribed since the fifties were associated with an unfavourable risk profile that led to numerous withdrawals. Medications issued from pharmaco-chemistry that mainly target brain amines to reduce appetite have been abandoned because of potential cardiovascular and neuropsychiatric toxicities. More recently, biological medications emerged, especially GLP-1 (Glucagon-Like Peptide-1) receptor agonists, well-known to manage type 2 diabetes and now recommended at higher doses for the treatment of obesity (liraglutide, semaglutide). A dual agonist that targets both GLP-1 and GIP (Glucose-dependent Insulinotropic Polypeptide) receptors (tirzepatide) appears to be even more potent as glucose-lowering agent and is currently tested as an anti-obesity agent. Many other pharmacological approaches are currently investigated but they should not mask the importance of life-style measurements.

Glucagon-like peptide-1 (GLP-1) receptor agonists have a privileged place in the management of type 2 diabetes (T2D). They not only improve glucose control without inducing hypoglycaemia and trigger weight loss, but also protect against atherosclerotic cardiovascular disease. Increasing the dose of three of them (liraglutide, semaglutide, dulaglutide) allows better glycaemic results and of potential interest a greater weight reduction. Liraglutide at a daily dose of 3.0 mg and semaglutide at a weekly dose of 2.4 mg received the indication for the therapy of obesity. A recent innovation consists in the development of dual unimolecular agonists that target GLP-1 and GIP («glucose-dependent insulinotropic polypeptide») receptors (tirzepatide) or GLP-1 and glucagon receptors (cotadutide). Tirzepatide, in the SURPASS programme, showed impressive reductions in glycated haemoglobin level and body weight, greater than those observed with dulaglutide or semaglutide. Tirzepatide received the indication of the treatment of T2D and is currently tested in obesity (SURMOUNT programme). Interestingly, triagonists GIP/GLP-1/glucagon are currently developed for the management of T2D and obesity, with also perspectives for treating metabolic-associated fatty liver disease.

Tirzepatide is a unimolecular dual agonist of both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, which is developed as once-weekly injection for the treatment of type 2 diabetes. Because of the complementarity of action of the two incretins, tirzepatide showed, in a dose-dependent manner (5, 10 and 15 mg), a better efficacy (greater reduction in HbA1c and body weight) compared with placebo, basal insulin and two GLP-1 analogues (dulaglutide and semaglutide) in the SURPASS program. Its cardiovascular protection (versus dulaglutide) is currently tested in SURPASS-CVOT. Finally, studies for the treatment of obesity and metabolic associated fatty liver disease are also ongoing. Gastrointestinal tolerance of tirzepatide appears comparable to that of GLP-1 analogues, except more diarrhoea., Competing Interests: Le Pr André J. Scheen déclare avoir reçu des honoraires comme orateur et/ou membre d’un conseil scientifique de la part des firmes AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Merck Sharp & Dohme, Novartis, NovoNordisk et Sanofi. Il a été investigateur clinicien dans les études LEADER, HARMONY Cardiovascular et PIONEER-6 avec des analogues du GLP-1 et est actuellement co-investigateur dans l’essai SURPASS-CVOT. Le Pr Régis P. Radermecker est investigateur principal pour le CHU de Liège dans l’essai SURPASS-CVOT. L’auteur de cet article n’a pas de conflit d’intérêts en rapport avec la présente publication. Les honoraires reçus de l’industrie pharmaceutique par Radermecker sont disponibles sur le site betransparent.be. Le Pr Nicolas Paquot est co-investigateur principal pour le CHU de Liège dans l’essai SURPASS-CVOT. Il déclare avoir reçu des honoraires comme orateur et/ou membre d’un conseil scientifique de la part des firmes AstraZeneca, Boehringer Ingelheim, Lilly, MSD Belgium, NovoNordisk, Fresenius et Sanofi.

Some sodium-glucose cotransporter type 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have proven their ability to reduce major cardiovascular events in patients with type 2 diabetes at high cardiovascular risk. Furthermore, SGLT2is reduce the risk of hospitalization for heart failure and the progression of renal disease. The 2018 ADA-EASD consensus gave the preference to either SGLT2is or GLP-1 RAs to prevent these complications. Underlying protective mechanisms are complex, differ between the two pharmacological classes and are potentially complementary, thus providing a rationale for a combination in patients at very high risk. Some studies already showed positive complementary effects on glucose control, body weight and arterial blood pressure, but not on cardiovascular and/or renal outcomes yet., Competing Interests: A. Scheen déclare avoir reçu des honoraires comme orateur, membre d’un conseil scientifique ou investigateur clinicien de la part des firmes AstraZeneca, Boehringer Ingelheim, Janssen, Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Sanofi et Servier. A. Scheen a été investigateur clinicien dans les études EMPA-REG OUTCOME, CANVAS-R, DECLARE-TIMI 58, LEADER et HARMONY OUTCOMES.

Two classes of antidiabetic agents have shown a cardiovascular and renal protection in patients with type 2 diabetes and high cardiovascular risk. Empagliflozin, a sodium-glucose cotransporter type 2 (SGLT2) inhibitor, and liraglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, were granted a reduction of major cardiovascular events and mortality after the positive results of EMPA-REG OUTCOME and LEADER outcome trials, respectively. Protection mechanisms most probably differ between the two pharmacological classes and are perhaps complementary. The question that may arise in clinical practice is to know which drug should be selected between these two options in a patient with type 2 and established cardiovascular disease, before considering a potential combination. The aim of this article is to discuss about the best therapeutic choice according to the patient individual profile and the specificities of each molecule.

Type 2 diabetes therapy has expanded considerably over the last decade. Two anti-diabetic therapeutic groups, which are GLP-1 (glucagon-like peptide-1) receptor agonists and SGLT2 inhibitors (sodium-glucose co-transporter-2), have shown efficacy not only on glycemic control but also on weight and other parameters that will be detailed in this article. Cardiovascular safety studies for two of these molecules were shown for the first time to decrease overall and cardiovascular mortality. The combination of these two therapeutic classes provides a logical solution due to their different mechanisms of action. The DURATION-8 study designed to demonstrate the benefits of this combination will also be discussed in this article., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article (Claire Ritz, Jaafar Jaafar). Jacques Philippe a reçu des honoraires pour des conférences et Advisory Board d’AstraZeneca et Boehringer Mannheim et des subsides de recherche de Novo Nordisk.

Dulaglutide (Trulicity®) is a new once-weekly agonist of Glucagon-Like Peptide-1 (GLP-1) receptors indicated in the treatment of type 2 diabetes. Phase III clinical trials in AWARD programme demonstrated the efficacy and safety of dulaglutide in patients with type 2 diabetes treated by diet and exercise, metformin, a combination of metformin and a sulfonylurea or metformin and pioglitazone or even by supplements of prandial insulin. In the AWARD programme, dulaglutide (subcutaneous 0.75 or 1.5 mg once weekly) exerted a greater glucose-lowering activity than metformin, sitagliptin, exenatide or insulin glargine, and was non-inferior to liraglutide 1.8 mg once daily. Dulaglutide is currently reimbursed in Belgium after failure of and in combination with a dual oral therapy with metformin and a sulfonylurea or metformin and pioglitazone.