This is the peer reviewed version of the article, accepted for publication in Andrology. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use ofSelf-Archived Versions.
Even before sodium-glucose cotransporter inhibitors (SGLTi) became popular agents for the treatment of people with type 2 diabetes (T2DM), clinicians had explored their potential as adjunct therapies in type 1 diabetes (T1DM). Several trials have demonstrated improved glycemic control (compared with placebo) and a decrease in glucose variability with a clinically relevant increase of time in range. In addition, weight loss and decreased systolic blood pressure are observed. The magnitude of the effects observed depends on the type of SGLTi, the dose administrated, and the duration of observation in the studies. As seen in T2DM, there was an increase in the risk of urogenital mycotic infections, but no increase in the risk of severe hypoglycemia. However, concerns arose regarding an increase in incidence of diabetic ketoacidosis. Mitigation strategies, including careful patient selection, extensive education of patients and (para)medical personnel, adequate insulin dose titration, and the adoption of a ketone-centered approach, are suggested. In different areas of the world, SGLTi are approved for use in T1DM with restrictions concerning patient selection and SGLTi dose. Real-world data on the effect of introduction of SGLTi in people with T1DM will yield insight on the robustness of glycemic effects over time, and allow us to determine whether the positive risk–benefit profile observed in clinical trials can be translated to the real world.
There is a clear unmet clinical need in people with Type 1 diabetes (T1DM) considering present day insulin therapy. New insulin analogues and novel technologies allowing more tailored insulin administration have improved the quality of life of people with T1DM, but issues like hypoglycemia, weight gain and variability in glucose profiles remain problematic. Areas covered: In this review, the clinical efficacy, safety and tolerability of dapagliflozin, a sodium-glucose cotransporter type 2 inhibitor, in type 1 diabetes (T1DM) is described based on a review of phase 2 and 3 studies to date. Expert opinion: Dapagliflozin has shown promising results as an adjunct therapy in T1DM, resulting in better glucose control, weight loss and lower blood pressure. No increase in hypoglycemia risk, in particular severe hypoglycemia, was observed, but, in comparison with reports in Type 2 diabetes (T2DM), genital infections were more prevalent. Dapagliflozin use was accompanied with decreases in insulin doses, but, to date, only a low risk of diabetic ketoacidosis (DKA) was reported. However, caution is needed when interpreting this data, arising from well controlled clinical trials, with intensive education programs around ketone measurements and DKA prevention. Further studies will need to establish how high the DKA risk is and how to mitigate this in a real-world setting.
The ADA/EASD consensus 2022 and its implications for Belgium
During the European Association for the Study of Diabetes (EASD) congress in Stockholm, the new consensus guideline for the treatment of hyperglycemia in type 2 diabetes was presented. The American Diabetes Association (ADA) and the EASD plead for a holistic, patient-centered approach surrounded by a team of healthcare professionals. The consensus focuses on a patient-tailored pharmacological and non-pharmacological approach taking into account patient-specific comorbidities. Striving for sustainable weight reduction should be the cornerstone of any therapeutic intervention in type 2 diabetes. The early initiation of combination therapy is recommended to avoid therapeutic inertia and to increase the time to therapeutic failure. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1-RA) remain the first choice for patients with established cardiorenal disease or high-risk patients, possibly in combination with metformin. In the absence of cardiovascular or renal disease, the medication selection should be driven by weight control, obtaining glycemic control and the avoidance of hypoglycemia. Here again, SGLT2i and GLP1-RA shine because of their good safety profile and highly favorable effects on weight, glucose and blood pressure. Thanks to the b(l)ooming development of new antidiabetic medication for type 2 diabetes, adding insulin to the treatment plan can often be postponed to later stages of the disease. When insulin is required, the combined initiation with a GLP1-RA should be considered as they allow lower glycemic targets to be reached with a lower injection burden, a lower risk of hypoglycemia and lower weight gain than with insulin alone.
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