ABSTRACT
Adipose tissue can be divided into white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue, according to the differences in morphology. WAT acts as a buffer for increased energy intake and decreased energy expenditure during the development of obesity, resulting in visceral and ectopic WAT accumulation. These WAT depots are strongly associated with chronic systemic inflammation, insulin resistance, and cardiometabolic risk related to obesity. They represent a primary weight loss target in anti-obesity management. Second-generation anti-obesity medications glucagon-like peptide-1 receptor agonists (GLP-1RAs) cause weight loss and improve body composition by reducing visceral and ectopic fat depots of WAT, resulting in improved cardiometabolic health. Recently, the understanding of the physiological significance of BAT beyond its primary function in generating heat through non-shivering thermogenesis has been expanded. This has raised scientific and pharmaceutical interest in the manipulation of BAT to further enhance weight reduction and body weight maintenance. This narrative review focuses on the potential impact of GLP-1 receptor agonism on BAT, particularly in human clinical studies. It provides an overview of the role of BAT in weight management and highlights the need for further research to elucidate the mechanisms by which GLP-1RAs affect energy metabolism and weight loss. Despite encouraging preclinical data, limited clinical evidence supports the notion that GLP-1RAs contribute to BAT activation.
Subject(s)
Adipose Tissue, Brown , Cardiovascular Diseases , Glucagon-Like Peptide-1 Receptor , Obesity , Humans , Adipose Tissue, Brown/metabolism , Adipose Tissue, White/metabolism , Cardiovascular Diseases/metabolism , Energy Metabolism , Glucagon-Like Peptide 1/metabolism , Obesity/metabolism , Thermogenesis , Weight Loss , Glucagon-Like Peptide-1 Receptor/agonists , AnimalsABSTRACT
BACKGROUND: With recent developments in diabetes technology, attaining adequate glucose control is more achievable than ever. Despite these improvements, a significant proportion of individuals with type 1 diabetes do not reach recommended glycaemic goals. Sodium-glucose co-transporter-2 (SGLT2) inhibitors are glucose-lowering agents that inhibit the reabsorption of filtered glucose in the kidneys, thus promoting glucosuria. Because the glucose-lowering effect of SGLT2 inhibitors is achieved independently of insulin secretion, it has been speculated whether they could bridge the gap towards achieving glycaemic targets in individuals with type 1 diabetes. SUMMARY: Our main goal was to systematically map the current knowledge on the efficacy and safety of SGLT2 inhibitor use in adults with type 1 diabetes and present recent studies regarding the use of SGLT2 inhibitors in youth with type 1 diabetes. Using a scoping review approach, we searched MEDLINE to identify relevant clinical trials of SGLT2 inhibitors as adjunctive therapy to insulin in type 1 diabetes published from January 31, 2012, to January 31, 2022. We included the most relevant, large-scale, and long placebo-controlled clinical trials of SGLT2 inhibitors as an add-on therapy to insulin in adults with type 1 diabetes. Additionally, we included all relevant pilot studies evaluating the use of SGLT2 inhibitors as add-on therapy to insulin in youth with type 1 diabetes. We identified eight placebo-controlled clinical trials in adults with type 1 diabetes meeting our inclusion criteria and two relevant pilot studies in youth with type 1 diabetes. The clinical trials in adults with type 1 diabetes confirmed the efficacy of SGLT2 inhibitors as add-on therapy to insulin. However, this was associated with an increased incidence of diabetic ketoacidosis (DKA) versus placebo in all identified clinical trials. The two relevant pilot studies in youth with type 1 diabetes showed promising results of SGLT2 inhibitor use as an add-on therapy to insulin, especially when combined with a fully closed-loop system. KEY MESSAGES: SGLT2 inhibitors, as an add-on therapy to insulin, improve glycaemic outcomes in adults with type 1 diabetes with a potential cost of increasing DKA risk. The use of add-on SGLT2 inhibitors to insulin shows promising results in youth with type 1 diabetes. Moreover, SGLT2 inhibitors as add-on therapy in combination with closed-loop insulin therapy could provide additional benefits in improving glycaemic control. The current role of SGLT2 inhibitors as an adjunct therapy to insulin in individuals with type 1 diabetes is yet to be determined.
