Integration of a fasting-mimicking diet programme in primary care for type 2 diabetes reduces the need for medication and improves glycaemic control: a 12-month randomised controlled trial

Abstract

Aims/hypothesis: The aim of this study was to evaluate the impact on metabolic control of periodic use of a 5-day fasting-mimicking diet (FMD) programme as an adjunct to usual care in people with type 2 diabetes under regular primary care surveillance.

Methods: In this randomised, controlled, assessor-blinded trial, people with type 2 diabetes using metformin as the only glucose-lowering drug and/or diet for glycaemic control were randomised to receive 5-day cycles of an FMD monthly as an adjunct to regular care by their general practitioner or to receive regular care only. The primary outcomes were changes in glucose-lowering medication (as reflected by the medication effect score) and HbA_1c levels after 12 months. Moreover, changes in use of glucose-lowering medication and/or HbA_1c levels in individual participants were combined to yield a clinically relevant outcome measure ('glycaemic management'), which was categorised as improved, stable or deteriorated after 1 year of follow-up. Several secondary outcome measures were also examined, including changes in body weight.

Results: One hundred individuals with type 2 diabetes, age 18-75 years, BMI ≥27 kg/m², were randomised to the FMD group (n=51) or the control group (n=49). Eight FMD participants and ten control participants were lost to follow-up. Intention-to-treat analyses, using linear mixed models, revealed adjusted estimated treatment effects for the medication effect score (-0.3; 95% CI -0.4, -0.2; p<0.001), HbA_1c (-3.2 mmol/mol; 95% CI -6.2, -0.2 and -0.3%; 95% CI -0.6, -0.0; p=0.04) and body weight (-3.6 kg; 95% CI -5.2, -2.1; p<0.001) at 12 months. Glycaemic management improved in 53% of participants using FMD vs 8% of control participants, remained stable in 23% vs 33%, and deteriorated in 23% vs 59% (p<0.001).

Conclusions/interpretation: Integration of a monthly FMD programme in regular primary care for people with type 2 diabetes who use metformin as the only glucose-lowering drug and/or diet for glycaemic control reduces the need for glucose-lowering medication, improves HbA_1c despite the reduction in medication use, and appears to be safe in routine clinical practice.

Trial registration: ClinicalTrials.gov NCT03811587 FUNDING: The project was co-funded by Health~Holland, Top Sector Life Sciences & Health, the Dutch Diabetes Foundation and L-Nutra.

Keywords: Diet; Fasting-mimicking diet; Glucose-lowering medication; HbA1c, Lifestyle; Primary care; Randomised controlled trial; Therapy; Type 2 diabetes.

Fig. 1

Study flow chart. n^a indicates the number of participants for whom this was the reason for being lost to follow-up or discontinuing FMD; there may be several reasons per participant

Fig. 2

Change over time in total MES, HbA_1c and HbA_1c corrected for medication use by adding total MES for the FMD group and the control group (ITT analysis). Values are means ± SEM at baseline, 6 months and 12 months. The numbers of participants per timepoint and per group are shown in Table 3. (a) Change in MES over time. (b) Change in HbA_1c (mmol/mol) over time. (c) Change in HbA_1c (%) over time. (d) Change in HbA_1c corrected for the total MES over time. *p<0.05; **p<0.01; ***p<0.001 vs the control group

Fig. 3

Effect of the FMD on use of glucose-lowering medication and HbA_1c levels in participants in the FMD group and the control group at 12 months (ITT analysis). Bars represent the percentage of participants in each category (total n=43 in the FMD group vs n=39 in the control group). Differences between the FMD group and the control group were evaluated using χ² test. The categories are defined in Table 1. (a) Change in use of glucose-lowering medication at the end of the study compared with baseline. (b) Change in HbA_1c at the end of the study compared with baseline. (c) Glycaemic management at the end of the study compared with baseline

Fig. 4

Overview of glucose-lowering medication used at baseline and after 12 months in the FMD group and the control group (ITT analysis). (a) Use of glucose-lowering medication in the FMD group at baseline (n=43). (b) Use of glucose-lowering medication in the control group at baseline (n=39). (c) Use of glucose-lowering medication in the FMD group after 12 months (n=43). (d) Use of glucose-lowering medication in the control group after 12 months (n=39). DPP4 inhibitor, dipeptidyl peptidase-4 inhibitor; GLP-1 agonist, glucagon-like peptide-1 agonist