Arias-Córdova et al. [36]
MexicoRCTTo assess the effects of NBS and HMS on GC and GV in patients with T2D when treatments were matched for digestible starch content.All participants with T2D treated with metformin or a combination of glibenclamide and metforminn = 1048.5 ± 9.12Not ApplicableNBS, HMS and DMS.
including three treatment phases, each with a duration of 4 days, and washout period between treatments of 9-day.The intake of NBS showed a reduction in fasting glycemia compared to DMS.Birkeland et al. [37] NorwayRCTTo examine the effect of inulin-type fructans on faecal microbiota and SCFAs in patients with T2D.T2D, with 2/3 of participants receiving glucose-lowering drugsn = 25 4.7 (0.2–20.0)16 g Inulin-type fructans versus 16 g maltodextrin.
There was 4-week washout which separated the 6 weeks treatment period.There was moderate, but significant increase in faecal levels of bifidobacteria in the group supplemented daily with inulin-type fructans.Candela et al. [38] ItalyRCTTo explore the effect of microbiotic Ma-Pi 2 diet in modulating gut microbiota dysbiosis in patients with T2D.Patients with T2DMa-Pi 2 diet:
n = 21
Control diet:
n = 1966Not ApplicableFibre rich microbiotic Ma-Pi 2 diet is enriched with complex carbohydrates, legumes, fermented products, sea salt and green tea.FBG and PBG were reduced significantly in both Ma-Pi 2 and control diets, although this was significantly higher in the Ma-Pi 2 diet compared to control. Both diets were also effective in supporting the recovery of health promoting SCFA producing bacteria including Faecalibacterium, Roseburia, Bacteroides and Akkermansia. Increases in Collinsella and Streptococcus were only counteracted by Ma-Pi 2 diet.Gonai et al. [39]
JapanRCTTo explore the effects of GOS on on glycaemia, gut microbiota and metabolitic parameters in patients with T2D.Patients with T2DGOS group: 28
Placebo group: 27GOS group: 55 ± 11
Placebo group: 54 ± 12GOS group: 10 ± 8
Placebo group: 6 ± 510 g/d GOS syrup versus 10 g/d maltodextrin syrup. 4 weeks of treatment.After consumption of GOS, Bifidobacteriaceae was significantly restored in patients with T2D, whereas lipopolysaccharide binding protein and glucose tolerance did not show improvement.Gu et al. [40]
ChinaRCTTo compare the effect of Acarbose versus sulfonylurea Glipizide on metabolic parameters, (e.g., glycaemic, control plasma BAs), and the intestinal microbiota, and discriminate such changes from disease-dependent alterations.Patients with T2DAcarbose group: 51
Glipizide group: 43Acarbose group:
53 ± 7
Glipizide group:
54 ± 7Not ApplicableAcarbose treatment versus Glipizide treatment.
A 3-month treatment period.Both the acarbose and glipizide groups improved glycemic control, with no significant differences. Acarbose increased the relative abundances of Lactobacillus and Bifidobacterium and depleted Bacteroides. However, Glipizide treatment did not affect the relative abundances at species-level. After 3 months of treatment, reductions in BW and BMI were more significant in the Acarbose group compared to the Glipizide group.Medina-Vera et al. [31]
MexicoRCTTo assess functional food-based dietary intervention on biochemical parameters and faecal microbiota in patients with T2D.Patients with T2DDP group: n = 28
Placebo group: n = 25DP group:
50.4 ± 8.7
Placebo group:
49.8 ± 10.6DP group:
4.1 ± 3.5
Placebo group:
4.4 ± 3.9A dietary portfolio, DP (14 g of dehydrated nopal, 4 g of chia seeds, 30 g of soy protein and 4 g of inulin) versus placebo (28 g of calcium caseinate and 15 g of maltodextrin). The treatment period was for 3 months.Consumption of DP promoted the abundance of Bifidobacterium longum which has been reported to improve insulin sensitivity.
There was significant reduction in the levels of HbA1c in patients with T2D in the DP group.Pedersen et al. [32]RCTTo investigate the effects of prebiotic supplementation on intestinal bacteria in patients with type 2 diabetesPatients with type 2 diabetesPrebiotic group: n = 14
Placebo group: n= 15Prebiotic group (56.7 ± 6.0)
Placebo group (58.1 ± 6.6)Prebiotic group (4.6 ± 2.2)
Placebo group (4.0 ± 3.1)Prebiotic (galacto-oligosaccharide mixture) or placebo (maltodextrin supplements each given 5.5g/day for 12 weeks.Prebiotic fibre supplementation did not improve glucose control or abundance of bacteria compared with control.Reimer et al. [41]
CanadaRCTTo assess the effect of the soluble viscous fibre PGX on glycemic control in adults withT2D.T2D patientsPGX group:
n = 147;
Placebo group:
n = 143PGX group:
56.2 ± 8.6
Placebo group:
53.4 ± 9.9Not ApplicablePGX (15–20 g/day) versus placebo (rice flour, 6.4–8.6 g/day) 52 weeks of treatmentPGX group increased Roseburia and led to a sustained reduction in HbA1c and FBG compared to placebo.Shin et al. [42]
KoreaRCTTo investigate whether the combination of SB and metformin influenced T2D symptoms.T2D on 500 mg/day metforminn = 12SB + Metformin: 63.1
Placebo: 63.1Not ApplicableSB (3.52 g SB extract) + metformin versus placebo+ metformin.
A 4-week washout separated the 8 weeks of treatmentLactobacillus and Akkermansia, showed significant increases after SB + metformin treatment.
The glucose, HbA1c and BMI were not changed after 8 weeks of SB and placebo treatment.Soare et al. [43]
ItalyRCTTo compare the effects of the Ma-Pi 2 diet and the dietary guidelines for T2D recommended by professional societies in Italy on T2D patients.Overweight or obese (BMI:27–45 kg/m2), aged 40–75 years affected by T2DMa-Pi 2 diet:25
Control diet:26Ma-Pi 2 diet:
67 ± 8.16
Control diet:
65 ± 7.28Ma-Pi 2 diet:7 ± 7.793
Control diet:4.5 ± 8.845Fibre-rich Ma-Pi 2 macrobiotic diet versus recommended diet of type 2 diabetes by professional societies.
3 weeks of treatment.The patients that received Ma-Pi 2 diet showed significant reduction in FBG, PBG, HbA1c, and BMI compared to those receiving the recommended diet for T2D.Soare et al. [44]
ItalyRCTTo investigate whether the benefits of Ma-Pi 2 extended beyond the 21-day intensive dietary intervention.Overweight or obese (BMI 27–45 kg/m2), aged 40–75 years affected by T2D. Ma-Pi 4 diet: 65 ± 8.89
Control diet:64 ± 8.15Ma-Pi 4 diet: 7 ± 7.41
Control diet: 4 ± 6.67Fibre-rich Ma-Pi 4 macrobiotic diet versus recommended diet of T2D diabetes by professional societies.
6 months of treatment.The Ma-Pi 4 diet had great improvement in glycemic control, compared with the control group.
Body weight loss was also observed in Ma-Pi 4 group, but was not significantly different compared to the control group.Su et al. [45]
ChinaRCTTo evaluate the effects of acarbose add-on therapy on gut microbiota and inflammatory cytokines among Chinese patients with T2D.Patients with T2D that did not receive acarbose for at least 1 month.Acarbose group: 59
Control group: 36Acarbose group:
55.7  ±  11.0
Control group:
56.5  ±  10.2Not Applicable50 mg acarbose (t.i.d) a day with meals together with oral antidiabetic drugs and/or insulin or insulin analogs versus similar antidiabetic treatment to interventional group but without acarbose.
Four weeks of treatment.Treatment with acarbose can increase the abundance of Bifidobacterium longum in patients with T2D and improve glycemic control.Tong et al. [46]
ChinaRCTTo evaluate the role of gut microbiota during improvements in hyperglycemia and hyperlipidemia by two drugs: metformin and AMC for diabetic patients with hyperlipidemia.Patients with
T2D and Hyperlipidemia.Metformin group: 100
AMC group: 100Metformin group: 58.55 ± 9.17
AMC group: 59.00 ± 9.46Not ApplicableAMC twice daily versus metformin tablets 0.25 g/time and 3 times/day. 12 weeks of treatment.The effect of AMC in regulating the microbes in the gut and in improving HOMA-IR and triglyceride levels was more profound compared with metformin.van Bommel et al. [47]
NetherlandsRCTTo examine the effects of 12-week treatment with the SGLT2 inhibitor dapagliflozin and sulphonylurea gliclazide on gut microbiome composition in patients with T2D treated with metformin.All participants with T2D treated with metformin as monotherapyDapagliflozin group:
n = 24;
Gliclazide group:
n = 17.Dapagliflozin group:
63 ± 7
Gliclazide group:
63 ± 7Dapagliflozingroup:
9.8 ± 4.1
Gliclazide group:
10.7 ± 7.310 mg dapagliflozin and 30 mg gliclazide.
Treatment for 12 weeks.Both dapagliflozin and gliclazide reduced HbA1c and FBG,
while BMI was reduced by dapagliflozin, but increased by gliclazide.Wu et al. [18]
SpainRCTTo investigate the effect of metformin on the composition and function of the microbiota.Individuals with type 2 diabetesMetformin group: n = 22
Placebo group: n = 18Metformin group: 52.6 ± 9.4
Placebo group: 54.9 ± 8.1Not applicableA start dose of 425 mg/day of metformin and increased progressively to reach 1700 mg/day or placebo (calorie restricted diet). Treatment was for four months.Metformin and not calorie restricted diet had significant effect on composition and function of the gut microbiota and reduction in HbA1c and fasting blood glucose levels.Zhao et al. [48]
ChinaRCTTo examine the effect of dietary fibre on SCFA-producing strains in patients with type 2 diabetes.Individuals with type 2 diabetesHigh fibre diet group: n = 27
Control group: n = 16High fibre diet group: 58.4 ± 32.2
Control group: 59.7 ± 24.0High fibre diet group: 8.0 ± 30.1
Control group: 7.9 ± 20High fibre diet composed of whole grains, traditional Chinese medicinal foods, and prebiotics.The presence of SCFA producers in greater diversity and abundance by fibre. Participants had better improvement in HbA1c levels.