Efficacy and safety of traditional Chinese medicine and SGLT2i, GLP‐1RA, and ACEI/ARB in the management of diabetic kidney disease: A systematic review and network meta‐analysis

Abstract Background In recent years, medications including sodium‐glucose cotransporter 2 inhibitors (SGLT2i), glucagon‐like peptide‐1 receptor agonists (GLP‐1RA), angiotensin‐converting enzyme inhibitors (ACEI), and angiotensin receptor blockers (ARBs) have been used to treat diabetic kidney disease (DKD). Increasing evidence has indicated that traditional Chinese medicine (TCM) can play an important role in these therapeutic approaches. To determine the most effective and safe therapeutic schedule for patients with DKD, a network meta‐analysis (NMA) was conducted. Methods Randomized‐controlled trials (RCTs) including the following treatment regimens were checked: conventional treatment regimen (Placebo); ACEI; ARB; SGLT2i; TCM; GLP‐1RA; ARB combined with GLP‐1RA (ARB + GLP‐1RA); ACEI combined with ARB (ACEI + ARB); ARB combined with SGLT2i (ARB + SGLT2i); ACEI combined with SGLT2i (ACEI + SGLT2i); ACEI combined with TCM (ACEI + TCM); ARB combined with TCM (ARB + TCM), GLP‐1RA combined with TCM (GLP‐1RA + TCM); GLP‐1RA combined with SGLT2i (GLP‐1RA + SGLT2i); SGLT2i combined with TCM (SGLT2i + TCM); and GLP‐1RA combined with ACEI (GLP‐1RA + ACEI) for treating patients with DKD. For dichotomous variables and continuous variables, odds ratios (ORs) and mean differences (MDs) were derived. A pairwise and NMA analysis was performed to compare serum creatinine (Scr), blood urea nitrogen (BUN), glycosylated hemoglobin (HbA1c), and 24‐h urinary total protein (24 h UTP). Thereafter, the interventions were ranked according to the surface under the cumulative ranking curve (SUCRA). Results A total of 87 RCTs were included in our study, including 16 different types of treatments and 10,485 patients. Compared with the placebo group, the ACEI + TCM group showed the best efficacy in relieving 24 h UTP and BUN (MD = −0.74 g/24 h, 95% confidence interval [CI]: −1.20 to −0.28 g/24 h, SUCRA = 97.2% and MD = −3.40 mmol/L, 95% CI: −4.90 to −1.80 mmol/L, SUCRA = 97.5%, respectively). In terms of reducing Scr, the ACEI + TCM group showed significant improvements compared to the placebo group (MD = −24.00 μmol/L, 95% CI: −34.00 to −13.00 μmol/L, SUCRA = 91.4%), followed by the GLP‐1RA + TCM and GLP1RA + SGLT2i groups (MD = −22.00 μmol/L, 95% CI: −32.00 to −12.00 μmol/L, SUCRA = 89.0% and MD = −20.00 μmol/L, 95% CI: −32.00 to −8.80 μmol/L, SUCRA = 85.1%, respectively). The ARB + GLP‐1RA, ACEI+ SGLT2i, and GLP‐1RA + TCM groups were ranked among the top three in terms of HbA1c (MD = −1.60%, 95% CI: −2.30% to −0.85%, SUCRA = 91.8%, MD = −1.50%, 95% CI: −2.70% to −0.35%, SUCRA = 85.1%, and MD = −1.30%, 95% CI: −1.80% to −0.73%, SUCRA = 81.5%, respectively). In terms of adverse events, the GLP‐1RA + TCM group had the highest safety, whereas headaches, dizziness, hypotension, hypoglycemia, and gastrointestinal symptoms were common adverse reactions in most treatment regimens. Conclusions The treatment scheme of ACEI + TCM may be the best choice to reduce 24 h UTP, BUN, and Scr in patients with DKD, while ARB + GLP‐1RA had the best effect in reducing HbA1c. In terms of drug safety, the GLP‐1RA + TCM group had the lowest incidence of adverse events.