Effect of SGLT-2 inhibitors on cardiac autonomic function in type 2 diabetes mellitus: a meta-analysis of randomized controlled trials

• Published in: Acta diabetologica 2023-01, Vol.60 (1), p.1-8
• Main Authors: Patoulias, Dimitrios, Katsimardou, Alexandra, Fragakis, Nikolaos, Papadopoulos, Christodoulos, Doumas, Michael
• Format: Article
• Language: English
• Subjects: Adult; Autonomic nervous system; Clinical trials; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetic neuropathy; Glucose transporter; Heart; Humans; Hypoglycemic Agents - therapeutic use; Internal Medicine; Medicine; Medicine & Public Health; Meta-analysis; Metabolic Diseases; Randomized Controlled Trials as Topic; Review Article; Sodium-Glucose Transporter 2 Inhibitors - adverse effects; Sodium-Glucose Transporter 2 Inhibitors - therapeutic use
• ISSN: 1432-5233; 0940-5429; 1432-5233
• DOI: 10.1007/s00592-022-01958-0

Background Cardiac autonomic neuropathy (CAN) is a common complication of type 2 diabetes mellitus (T2DM). We sought to determine whether sodium-glucose co-transporter-2 (SGLT-2) inhibitors affect indices of CAN in patients with T2DM. Methods We searched for parallel group or cross-over randomized controlled trials (RCTs) enrolling adult subjects with T2DM, assigned to a SGLT-2 inhibitor versus placebo or active comparator and addressing their effect on CAN. PubMed, Cochrane Library and gray literature sources were searched. We set as primary efficacy outcome the change in the low-frequency-to-high-frequency (LF/HF) ratio. We set as secondary efficacy outcomes: first, the change in the standard deviation of all 5 min mean normal RR intervals and second, the change in the square root of the mean of the sum of the squares of differences between adjacent RR intervals (r-MSSD). Protocol has not been registered at a publicly available repository. Results We pooled data from four RCTs in a total of 247 subjects with T2DM. SGLT-2 inhibitor treatment did not have a significant effect on LF/HF ratio (MD = − 0.11, 95% CI − 0.35 to 0.12, I 2  = 0%, p  = 0.36). SGLT-2 inhibitor treatment did not have a significant impact either on SDNN (MD = − 2.83, 95% CI − 7.41 to 1.75, I 2  = 31%, p  = 0.23), or on r-MSSD (MD = − 0.14, 95% CI − 3.52 to 3.25, I 2  = 46%, p  = 0.94). Overall risk of bias was graded as low across the selected RCTs. Conclusion SGLT-2 inhibitor treatment in patients with T2DM does not seem to provide any significant beneficial effect on CAN indices.