Avaliação da eficácia e segurança dos inibidores do cotransportador tubular do tipo 2 de sódio e glicose: revisão sistemática e meta-análise.

Abstract

Introduction: Type 2 diabetes is a global public health concern, increasing the risk of cardiovascular events and mortality. The WHO predicts a rise in cases by up to 300 million by 2045. While hyperglycemia affects organs and causes complications, its impact on cardiovascular complications remains unclear. Some hypoglycemic drugs increase the risk of heart failure, and new therapies, such as SGLT2 inhibitors, show benefits beyond glycemic control. Justification and Objectives: This study aims to assess the efficacy and safety of sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) in the treatment of adult patients with type 2 diabetes (T2DM). Methodology: A systematic review with meta-analysis was conducted, searching databases from January 2014 to October 2023, including randomized clinical trials evaluating the efficacy and safety of SGLT2 inhibitors in T2DM treatment, HbA1C reduction, major cardiovascular events (MACE) risk, and adverse events, with the quality of evidence assessed by the GRADE system. This systematic review was registered via PROSPERO CRD42022362775. Results: SGLT2 inhibitors resulted in significant 38% reduction in the risk of cardiovascular deaths and hospitalizations for heart failure compared to conventional diabetes therapy. However, there was no significant reduction in the risk of major cardiovascular events. Furthermore, they showed a significant reduction in the progression of chronic kidney disease. There was no significant increase in the risk of hypoglycemia, fractures, or volume depletion, but there was an increased risk of genitourinary mycotic infections. Discussion: There are benefits in reducing hospitalizations for heart failure and the progression of kidney disease. However, there was no significant reduction in cardiovascular mortality when excluding hospitalizations for heart failure. The analysis also highlighted challenges in collecting complete data and safety concerns regarding hypoglycemia, fractures, orthostatic hypotension, and genitourinary mycotic infections. Additional trials are needed to clarify these issues. The analysis considered the need to stratify patients at increased risk of mycotic infections and suggested that SGLT2 inhibitors may be safe in patients with a low risk of urinary tract infections. However, the lack of transparency regarding treatment discontinuation reasons and the use of a more appropriate comparator group were identified as limitations in the analysis. Conclusion: SGLT2 inhibitors significantly reduce hospitalizations for heart failure and slow the progression of renal disease. However, their effectiveness in MACE and glycated hemoglobin reduction is limited. The predominantly Caucasian profile of participants underscores the necessity for further investigations in non-Caucasian populations. Additionally, safety outcomes in specific groups indicate the imperative need to establish stringent criteria for the introduction of these medications in individuals with type 2 diabetes.