Efficacy and Safety of SGLT2 Inhibitors in the Treatment of Type 2 Diabetes: An Umbrella Review
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Objective
While sodium-glucose co-transporter 2 (SGLT2) inhibitors offer a novel, insulin-independent approach to managing type 2 diabetes (T2DM), their overall benefit-risk profile, encompassing cardio-renal outcomes and long-term safety, requires a comprehensive synthesis of the evidence. This umbrella review aims to definitively evaluate the efficacy and safety of SGLT2 inhibitors in patients with T2DM.
Methods
This umbrella review systematically searched major databases for relevant systematic reviews and meta-analyses up to September 2025. The methodological quality and certainty of evidence were assessed using AMSTAR 2 and GRADE tools.
Results
SGLT2 inhibitors demonstrated significant benefits in glycemic control (HbA1c WMD: −0.52% to −0.56%), body weight (MD: −1.76 to −2.63 kg), and systolic blood pressure (WMD: −4.08 mmHg). They also showed marked cardio-renal protection, reducing risks of major adverse cardiovascular events (RR=0.85), hospitalization for heart failure (RR=0.67), cardiovascular death (RR=0.75), all-cause mortality (RR=0.79), and composite renal outcomes (RR=0.59–0.64). Additionally, they positively modulated inflammatory markers and adipokines. However, these benefits were counterbalanced by increased risks of genital infections (OR=3.57), urinary tract infections (OR=1.34), and diabetic ketoacidosis (OR=2.19). The overall quality of evidence was generally low to very low.
Conclusion
SGLT2 inhibitors offer a multi-faceted therapeutic option for T2DM, providing glycemic, cardiovascular, and renal benefits, which make them particularly valuable for high-risk patients. Clinicians should be aware of the associated adverse events. Future high-quality, long-term studies are warranted to strengthen these findings.
