RESUMO
BACKGROUND: Diabetes mellitus (DM) significantly impacts global health due to its complications and the economic burden it places on healthcare systems. The rise of novel once-weekly diabetes medications with different mechanisms of action necessitates an evaluation of their relative efficacy and safety. OBJECTIVES: This study compares the efficacy and tolerability of once-weekly insulin analogs (icodec and BIF) with once-weekly GLP-1/GIP agonists (semaglutide, exenatide, tirzepatide, dulaglutide) in managing type 2 diabetes mellitus (T2DM). METHODS: We conducted a network meta-analysis (NMA) using data from randomized controlled trials (RCTs) that compared these treatments with a baseline of daily basal insulin. Primary outcomes included changes in HbA1c, body weight, and tolerability. RESULTS: The analysis integrated data from 25 RCTs, involving 18,257 patients. Tirzepatide significantly outperformed other treatments in reducing HbA1c and promoting weight loss. Weekly insulins, compared to GLP-1/GIP agonists, showed a more tolerable profile and were beneficial for certain patient demographics emphasizing weight stability. CONCLUSION: Our findings suggest that while once-weekly GLP-1/GIP agonists provide superior glycemic control and weight management, weekly insulins offer viable options for patients prioritizing fewer side effects and weight stability. This comprehensive comparison aids in refining personalized treatment strategies for T2DM management.
RESUMO
BACKGROUND: Adaptive thermogenesis represents the main mechanism through which the body generates heat in response to external stimuli, a phenomenon that includes shivering and non-shivering thermogenesis. The non-shivering thermogenesis is mainly exploited by adipose tissue characterized by a brown aspect, which specializes in energy dissipation. A decreased amount of brown adipose tissue has been observed in ageing and chronic illnesses such as obesity, a worldwide health problem characterized by dysfunctional adipose tissue expansion and associated cardiometabolic complications. In the last decades, the discovery of a trans-differentiation mechanism ("browning") within white adipose tissue depots, leading to the generation of brown-like cells, allowed to explore new natural and synthetic compounds able to favour this process and thus enhance thermogenesis with the aim of counteracting obesity. Based on recent findings, brown adipose tissue-activating agents could represent another option in addition to appetite inhibitors and inhibitors of nutrient absorption for obesity treatment. PURPOSE: This review investigates the main molecules involved in the physiological (e.g. incretin hormones) and pharmacological (e.g. ß3-adrenergic receptors agonists, thyroid receptor agonists, farnesoid X receptor agonists, glucagon-like peptide-1, and glucagon receptor agonists) modulation of adaptive thermogenesis and the signalling mechanisms involved.