Both glucagon-like peptide 1 receptor agonists (GLP1rA) and insulin therapy are effective injectable therapies for the treatment of type 2 diabetes (T2D). Their actions are complementary to each other and their combination therefore provides an attractive therapeutic strategy. Indeed, in the latest guidelines from the American Diabetes Association, it was also recommended that combination therapy with a GLP1rA should be considered in patients on insulin therapy for greater efficacy and durability of treatment effect. Moreover, a fixed-ratio combination (FRC) product such as iGlarLixi consisting of glargine and lixisenatide, can be considered if patients are put on both GLP1rA and basal insulin therapy. ⁽¹⁾

However, intensification of treatment regimen is sometimes difficult in real-life due to multiple factors including clinical inertia of clinicians, patient preference, frequency of injections and convenience issues. The recently published Solimix study is a randomized controlled trial which demonstrated that in T2D patients who were sub-optimally controlled with basal insulin plus one or two oral anti-diabetic agents, the use of FRC for 6 months was non-inferior to premixed insulin therapy in glycaemic control and was superior in weight reduction, allowing a higher proportion of patients reaching their HbA1c goals, and at the same time, without weight gain and hypoglycaemia. ⁽²⁾

In this talk, the importance and difficulties during early intensification therapy in T2D patients will be presented. Moreover, the role of novel FRC as compared to other intensification strategies will also be discussed.

References:

1. American Diabetes Association Professional Practice C, Draznin B, Aroda VR, Bakris G, Benson G, Brown FM, et al. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S125-S43.
2. Rosenstock J, Emral R, Sauque-Reyna L, Mohan V, Trescoli C, Al Sifri S, et al. Advancing Therapy in Suboptimally Controlled Basal Insulin-Treated Type 2 Diabetes: Clinical Outcomes With iGlarLixi Versus Premix BIAsp 30 in the SoliMix Randomized Controlled Trial. Diabetes Care. 2021.

LDL-C is one of the key risk factors associated with plaque formation and CV events. International guidelines retain a treatment goal approach to lipid management with an individualized target depending on patients’ baseline CV risk level – with the higher the CV risk, the lower the target LDL-C. However, there is still a major gap in the achievement of LDL-C goal which may be due to the use of less intensive statins, or the lack of lipid-lowering agents’ combinations.

With an aim to minimize the gap, current guidelines recommend the combination of statin, ezetimibe and PCSK9 inhibitor in patients at very-high-risk not achieving LDL-C goal for secondary prevention. The addition of PCSK9 inhibitor to oral treatments had been proven in large clinical trial to substantially reduce LDL-C and to reduce CV event risk.  Apart from cholesterol lowering effect, recent studies also demonstrated the use of PCSK9 inhibitor could lead to favorable coronary plaque changes like plaque regression and stabilization. There are also several emerging lipid-lowering therapies which could significantly reduce LDL-C and we are waiting for their CV outcome and long-term safety results.

This presentation provides a review of the (1) hypercholesterolemia guideline recommendations; (2) clinical evidence and the anti-atherosclerotic effect of lipid-lowering therapies.

As kidney disease progresses, phosphorus retention also increases. Phosphate lowering therapy for hyperphosphataemia is key to the treatment of patients with chronic kidney disease -mineral and bone disorder (CKD-MBD).

Phosphate-binding compounds have evolved from the original aluminum-based binders pioneered in the 1970s to calcium-based binders such as calcium acetate, and more recently, Calcium-free phosphate binders are increasingly favoured since calcium-based agents potentially cause harmful calcium overload and vascular calcification that confound the benefits of reducing serum phosphorus. Randomised controlled studies consistently show that these Calcium-free agents offer equivalent lowering of serum phosphorus and often effectively achieve phosphorus targets, exert mortality benefits and other pleiotropic effects versus calcium salts.

This sharing summarizes (1) the rationale to start non-calcium-based therapies (2) the evidence of efficacy and safety for recent calcium-free phosphate binders in CKD-MBD management. Prof. Yap will also share ⁽²⁾ the treatment targets of CKD-MBD based on international recommendation and clinical consideration.