Comparative analysis of the efficacies of probiotic supplementation and glucose-lowering drugs for the treatment of type 2 diabetes: A systematic review and meta-analysis.

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• Glucose-lowering drugs, except for DPP-4i, reduced FBS and HbA1c more than probiotics; and SGLT-2i induced the greatest decrease in HbA1c
• A BMI ≥ 30 kg/m2 showed a significant decrease in FBS and the HOMA-IR index compared with those with lower BMI
• Weight loss induced by glucose-lowering drugs and probiotic supplementation plays an important role in glycaemic control in obese patients with type 2 diabetes.

Introduction

This meta-analysis compared the effects of probiotics and glucose-lowering drugs thiazolidinedione [TZD], glucagon-like pep-tide-1 receptor agonists [GLP-1 RA], dipeptidyl peptidase IV inhibitors, and sodium glucose co-transporter 2 inhibitors [SGLT-2i]) on various outcome measures in patients with type 2 diabetes (T2D).

Methods

A search was performed on PubMed, Web of science, Embase, and Cochrane Library between January 2015 - April 2021.

Results

25 randomised controlled trials (RCT) were included (2843 participants). 14 RCTs (842 participants) involved the administration of single probiotics, multi-strain probiotics, and probiotics with co-supplements, and 11 RCTs (2001 participants) involved TZD, GLP-1 RA, SGLT-2i, and DPP-4i. Participants in 7 of the studies had T2D, aged ≤ 55 years old. 8 RCTs included participants with a mean BMI ≥ 30 kg/m2, and 11 RCTs participants had a mean BMI < 30 kg/m2. Effects of probiotics:

• Fasting Blood Sugar (FBS): A reduction (−1.42, −0.32 mg/dL, p=0.000)
• Glycated hemaglobin (HbA1c): No reduction (p = 0.000)
• Insulin Resistance (HOMA-IR): A decrease (−0.64, −0.31; p = 0.780), regardless of probiotic strain or with a co-supplement
• Insulin: Not significant (p = 0.000). Subgroup analysis: no reduction
• Total Cholesterol (TC): No difference (p = 0.941). Subgroup analysis: reduction from multi-species probiotics (−0.36, −0.01 mg/dL, p = 0.871)
• Triglycerides: Difference (−0.25 mg/dL, p = 0.958)
• LDL-C: No changes (p = 0.189)
• HDL-C: No increase (p = 0.014)
• Systolic Blood Pressure (SBP): A decrease (−6.44, −0.08 mmHg, p = 0.044)
• Diastolic Blood Pressure (DBP): A reduction (−4.53, −0.80 mmHg, p = 0.206).

Effects of glucose-lowering drugs:

• FBS: A decrease (−4.22 mg/dL, −1.24 mg/dL, p = 0.000)
• HbA1c: A decrease (−2.51%, −0.52%, p = 0.000) with TZD, GLP-1 RA, SGLT-2i, and DPP- 4i; a reduction with SGLT-2i (p = 0.003)
• TC: No difference (p = 0.000). Subgroup: no decrease with single species probiotics and probiotics with co-supplements, TZD, GLP-1 RA, and DPP-4i)
• TG: No difference (p = 0.000)
• . HDL-C: No increase (p = 0.000). Subgroup: a decrease with TZDs (−2.37, −0.72 mg/dL). No difference with probiotic strains, or probiotics with co-supplements, GLP-1 RA, and DPP-4i
• LDL-C: No changes (p = 0.000), Subgroups: no difference with probiotic strains, probiotics with co-supplements, TZD, GLP-1 RA, and DPP-4i).

Limitations Limited number of studies for TZD and SGLT-2i, making results potentially unreliable.

Conclusions Multi species probiotics are worth considering as an adjunct to glucose-lowering drugs, and for improving lipid profiles and hypertension.

• Probiotic supplementation reduced the HOMA-IR index
• Multi-species probiotics were associated with reduction in TC and TG levels
• DPP-4i only decreased TG levels
• TZD was associated with decrease in HDL-C, whereas probiotic supplementation was associated with higher decrease in SBP and DBP and that GLP-1 RA increases the risk of hypoglycaemia.

• Semaglutide was associated with an increased risk for hypoglycaemia compared with a placebo, indicating that the safety of semaglutide needs further study
• Dietary and physical activity should be considered in future studies
• Heterogeneity in some indicators may be due to differences in study baseline characteristics,Larger trials needed to support the results of this meta-analysis.