Renal, cardiovascular, and safety outcomes of adding sodium–glucose cotransporter-2 inhibitors to insulin therapy in patients with type-2 diabetes: a meta-analysis

• Published in: International urology and nephrology Vol. 56; no. 2; pp. 557 - 570
• Main Authors: Zhang, Qian, Zhang, Qingqing, Yang, Liu, Yang, Shufang, Lu, Yu
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.02.2024; Springer Nature B.V
• Subjects: Blood pressure; Body Weight; Clinical trials; Creatinine; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - drug therapy; Epidermal growth factor receptors; Glomerular filtration rate; Glucose; Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents - adverse effects; Insulin; Insulin - adverse effects; Kidneys; Medicine; Medicine & Public Health; Nephrology; Nephrology - Review; Sodium; Sodium-glucose cotransporter; Sodium-Glucose Transporter 2 Inhibitors - adverse effects; Uric Acid; Urinary tract; Urology; Type-2 diabetes mellitus; Renal outcomes; Sodium–glucose cotransporter-2 inhibitors; Meta-analysis
• ISSN: 1573-2584; 0301-1623; 1573-2584
• DOI: 10.1007/s11255-023-03719-6

Aims To investigate the renal, cardiovascular, and safety outcomes when sodium–glucose cotransporter-2 inhibitors (SGLT2is) were added to insulin therapy in patients with type-2 diabetes mellitus (T2DM). Materials and methods We searched Embase, PubMed, and Cochrane libraries for reports published up to Feb 2023. Randomized controlled trials (RCTs) comparing SGLT2is and insulin combination therapy (SGLT2is + INS group) with insulin therapy alone (INS group) in T2DM were included. Results Fourteen RCTs involving six thousand one hundred twenty subjects with durations of 12–104 weeks were included. Compared with the insulin group, the SGLT2is + INS group showed decreased glycosylated hemoglobin values and insulin dosages ( P  < 0.00001). Meanwhile, the SGLT2is + INS group had a reduced urinary albumin/creatinine ratio (UACR) by 25.42 mg/g and uric acid concentration ( P  = 0.030; P  = 0.001, respectively) but the estimated glomerular filtration rate (eGFR) and renal-related adverse events were unaffected ( P  = 0.070; P  = 0.880, respectively). Blood pressure and body weight were lower in the SGLT2is + INS group ( P  < 0.01). However, the risk of genital infection was bigger when SGLT2is were added to insulin therapy ( P  < 0.00001), but the risks of severe hypoglycemia or urinary tract infection were equal between the two groups ( P  > 0.05). Conclusion Adding SGLT2is to insulin therapy in T2DM patients showed better glucose control and decreased albuminuria, uric acid, blood pressure, and body weight without a reduction in the eGFR.