Flow and characteristics of the included studies

The detailed process of the PRISMA flowchart is presented in Fig. 1. Initially, 599 published studies were identified after searching multiple databases, and 5 additional records were identified through other sources. After carefully screening and assessing eligibility, 33 studies [21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53] were found eligible and were included in the systematic review. It was noteworthy that one trial [47] included two well-matched RCTs and actually counted as 2 RCTs in our meta-analysis. Therefore, 33 trials (34 RCTs) were included in all.

Fig. 1 PRISMA flowchart indicating studies identified by and included in the systematic review Full size image

The study characteristics are presented in Table 1. Thirty-three clinical trials [21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53] involving 1346 participants were included, among which 23 trials were parallel RCTs [22,23,24,25,26, 28,29,30,31,32,33,34,35, 37, 39, 40, 44,45,46,47, 49,50,51] and 10 were crossover RCTs [21, 27, 36, 38, 41,42,43, 48, 52, 53]. Five studies [33, 39, 41, 46, 48] were conducted in healthy subjects, 7 studies [26, 28, 32, 44, 51,52,53] in the overweight and obesity populations and 14 studies (15 RCTs) [21, 22, 25, 29,30,31, 34, 35, 37, 38, 42, 45, 47, 49] in the prediabetes and T2DM population, and 7 studies [23, 24, 27, 36, 40, 43, 49] in the other group were performed mainly in non-alcoholic steatohepatitis patients [23, 24, 27, 40] or the elderly [43, 49]. The intervention substances varied among the included studies: 12 studies [25, 30, 34, 35, 37,38,39,40, 47, 48, 51, 52] used inulin only, and 4 studies [22, 23, 46, 50] used synbiotic (a combination of ITF and probiotics). The daily dose and duration of the intervention period varied between studies. The daily dose of ITF ranged from 5.5 to 30 g (median dose: 10 g/day), and the duration of the intervention periods ranged from 20 to 252 days (median duration: 56 days). Eligible outcomes of glycemic indicators were reported: FBG in 32 studies (33 RCTs) [21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37, 39,40,41,42,43,44,45,46,47,48,49,50,51,52,53], HbA1c in 11 studies (12 RCTs) [25, 29,30,31, 34, 35, 42, 45, 47], FINS in 25 studies (26 RCTs) [22,23,24, 26,27,28,29,30, 32,33,34,35, 37,38,39,40,41,42, 45,46,47,48,49, 52, 53], and HOMA-IR in 17 studies (18 RCTs) [22,23,24, 28, 30, 32, 34, 35, 37, 38, 40, 45,46,47,48,49, 52]. Except for one study [23], in which subjects were instructed to modify dietary intake in both the intervention and control groups, participants were advised to maintain their usual diet. The side effects were studied in 26 trials, and not mentioned in 7 others. Of the 26 trials, 19 explicitly reported all participants in the intervention and control groups had no adverse effects after substances supplementation, 5 showed no significant difference in the incidence of adverse effects between participants of the intervention and control groups, except some subjects in 2 studies [43, 44] were reported to suffer intestinal pressure, flatulence or abdominal discomfort.

Table 1 Characteristics of the included studies Full size table

Study quality

The quality of bias assessment of the included studies is shown in Additional file 2: Figure S1. According to the seven assessment criteria of the Cochrane Handbook for Systematic Review of Interventions, most of the studies had good quality although some were characterized by insufficient information among the random sequence generation, allocation concealment, binding of outcome assessment and other bias, which was on account of the financial or food assistance provided by companies. In addition, bias may exist in some studies because 3 trials [25, 32, 48] had a high dropout rate.

Main outcomes and GRADE certainty

We conducted a meta-analysis to assess the effect of ITF on glycemic indicators, including FBG, HbA1c, FINS, and HOMA-IR, and used GRADE to assess the results. The GRADE evidence profile for the summary of findings is presented in Table 2.

Table 2 GRADE profile of ITF supplementation for FBG, HbA1c, and FINS levels and HOMA-IR scores in the total population and in the prediabetes and T2DM population Full size table

To explore whether ITF supplementation affected hyperglycemia, FBG data were analyzed. The effects of ITF on FBG were reported in 33 RCTs, including 14 RCTs in the prediabetes and T2DM population. The overall meta-analysis showed that ITF supplementation significantly reduced FBG with a WMD of − 0.21 mmol/l (95% CI − 0.33, − 0.09 mmol/l; P = 0.0005) (moderate rate). However, significant heterogeneity was observed between studies (I2 = 59%, P < 0.0001) (Fig. 2). Importantly, we found a more significant reduction in FBG based on the prediabetes and T2DM population (WMD: − 0.60 mmol/l; 95% CI − 0.71, − 0.48 mmol/l; P < 0.00001) (high rate), but the reduction was not significant in other populations. Moreover, no heterogeneity was observed in the grouped analyses with all I2 = 0%.

Fig. 2 Forest plot displaying the effects of inulin-type fructans on fasting blood glucose (mmol/l) by subgroup Full size image

Next, we examined whether ITF supplementation affected long-term glycemic regulation by analyzing HbA1c data. The effect of ITF on HbA1c was reported in 12 RCTs, including 10 RCTs in the prediabetes and T2DM population. The overall analysis revealed that HbA1c was reduced significantly (WMD: − 0.39%; 95% CI − 0.65, − 0.13%; P = 0.003) (moderate rate). Notably, in the T2DM population, HbA1c showed a significant reduction with a WMD of − 0.58% (95% CI − 0.83, − 0.32%; P < 0.00001) (high rate), and no significant heterogeneity was observed across studies (I2 = 14%, P = 0.31) (Fig. 3).

Fig. 3 Forest plot displaying the effects of inulin-type fructans on glycosylated hemoglobin (%) by subgroup Full size image

Next, we analyzed the effect of ITF on the fasting insulin concentration. Twenty-six RCTs reported changes in FINS after ITF supplementation, including 11 RCTs in the prediabetes and T2DM population. Overall, ITF supplementation reduced FINS significantly with a WMD of − 1.22 µU/ml (95% CI − 1.90, − 0.54 µU/ml; P = 0.0005) (very low rate) (Fig. 4). In the prediabetes and T2DM population, FINS showed a more significant reduction (WMD: − 1.75 µU/ml; 95% CI − 2.87, − 0.63 µU/ml; P = 0.002) (low rate), and the reduction was not significant or was modestly significant in the other populations.

Fig. 4 Forest plot displaying the effects of inulin-type fructans on fasting insulin (μU/ml) by subgroup Full size image

Last, we also examined whether ITF supplementation affected insulin sensitivity by analyzing HOMA-IR. The effect of ITF on HOMA-IR was reported in 18 RCTs, among which 9 RCTs were based on the prediabetes and T2DM population. The overall analysis revealed that ITF supplementation significantly reduced HOMA-IR with a WMD of -0.57 (95% CI − 0.84, − 0.31; P < 0.0001) (low rate) (Fig. 5). In the prediabetes or T2DM subgroup, HOMA-IR also showed a significant reduction (WMD: − 0.69, 95% CI − 1.10, − 0.28, P = 0.001; I2 = 81%) (low rate).

Fig. 5 Forest plot displaying the effects of inulin-type fructans on homeostasis model assessment-insulin resistance (arbitrary units) by subgroup Full size image

In addition, to analyze the relative hypoglycemic effects, we calculated the weighted mean of the baseline and the hypoglycemic results of the four glycemic indicators (FBG, HbA1c, FINS, and HOMA-IR). In the prediabetes and T2DM population, compared with their control groups, the relative reduction of the four indicators reached − 7.15%, − 7.00%, − 16.58%, and − 25.34% of their baseline values in the supplementation group, which were − 4.68%, − 6.13%, − 13.06%, and − 17.83% in the total population, respectively. The relative effects in both the intervention and control groups are shown in Table 2.

Nonlinear dose–response analysis

We explored the recommended daily dose and duration of ITF for glycemic control by dose–response analysis. As shown in Fig. 6, in the prediabetes and T2DM population, the relationship curves suggested that ITF supplementation had effects on the glycemic indicators, and the effects were different with different daily doses, durations and total doses of ITF. When the daily dose was 10 g and the duration reached 42 days and longer, these four glycemic indicators were significantly reduced, and the effect of glycemic control was satisfactory; the results were robust because the number of supporting studies was relatively large. Figure 6g, j, although FINS and HOMA-IR kept a decreasing trend when the daily dose was above 10 g, the supporting studies were fewer, and the results were not as credible. In the duration relationship curve, a similar situation existed.

Fig. 6 a analysis between dose of inulin-type fructans and FBG net change level; b analysis between duration of inulin-type fructans and FBG net change level; c analysis between total dosage of inulin-type fructans and FBG net change level; d analysis between dose of inulin-type fructans and HbA1c net change level; e analysis between duration of inulin-type fructans and HbA1c net change level; f analysis between total dosage of inulin-type fructans and HbA1c net change level; g analysis between dose of inulin-type fructans and FINS net change level; h analysis between duration of inulin-type fructans and FINS net change level; i analysis between total dosage of inulin-type fructans and FINS net change level; j analysis between dose of inulin-type fructans and HOMA-IR net change level; k analysis between duration of inulin-type fructans and HOMA-IR net change level; l analysis between total dosage of inulintype fructans and HOMA-IR net change level. Full size image

These analyses were also performed in the total population (Additional file 3: Figure S2). The figure suggested that the overall trends of the curves were consistent with those of the prediabetes and T2DM population. For the HbA1c indicator, the trend of the dose–response relationship curves decreased rapidly at first and then rose gradually at some point.

Subgroup analyses

The subgroup analysis results are presented in Table 3. The results showed that the female subgroup had reductions in FBG, HbA1c, FINS and HOMA-IR, while only FINS was significantly reduced in the male subgroup. The subgroup results showed that inulin had better effects on HbA1c and HOMA-IR than other kinds of ITF and that ITF supplementation in drinks had better effects on the four glycemic indicators than that in other foods, such as cookies, bread and so on. The pooled results of 4 studies examining symbiotic (ITF and probiotic) supplementation showed a significant reduction in FINS and HOMA-IR but no significant effects on the other two indicators. The study design, study country, and whether the mentioned sponsor might also be factors influencing the differences in the results between the studies.

Table 3 Subgroup meta-analysis of the effects of inulin-type fructans on glycemic indicators (FBG, HbA1c, FINS and HOMA-IR) Full size table

Sensitivity analysis

The results of the leave-one-out sensitivity analysis suggested that the effects of ITF supplementation on all four glycemic indicators were robust and not significantly driven by any single study (Additional file 4: Figure S3).

In further sensitivity analyses, after the removal of high potential outlier studies that shifted the pooled mean difference more than 10%, the reanalysis results from the fixed effect model revealed no significant change after the exclusion compared with before. All the reanalysis results are summarized in Table 4.

Table 4 Reanalysis for the effects of inulin-type fructans on glycemic indicators (FBG, HbA1c, FINS and HOMA-IR) excluding high heterogeneity studies Full size table

Publication bias analyses

The publication bias of the included studies on the four indicators was inspected with a funnel plot and Egger’s test, and the results are shown in Additional file 5: Figure S4. The funnel plots of FBG, HbA1c and HOMA-IR were symmetrical, which may be interpreted as no publication bias and the same results were shown in Egger’s test (P > 0.05). However, the funnel plot and Egger’s test showed that there might be publication bias in the FINS results (t = − 2.24; 95% CI − 2.28, − 0.09; P = 0.035).