DPS 2001.

Methods	Parallel, randomised, controlled, clinical trial, randomisation ratio 1:1
Participants	Inclusion criteria: BMI ≥ 25 kg/m2; IGT (2‐h plasma glucose after an OGTT 140‐200 mg/dL (7.8‐11.0 mmol/L)) and FPG < 140 mg/dL (7.8 mmol/L) (WHO 1985), 40‐65 years Exclusion criteria: diagnosis of diabetes mellitus, involvement of people with regularly vigorous physical activity, chronic disease, diseases likely to interfere with glucose metabolism (e.g. liver disease), psychological or physical disabilities deemed likely to interfere with participation in the study Diagnostic criteria: IGT (2‐h plasma glucose after an OGTT 140‐200 mg/dL (7.8‐11.0 mmol/L)) and FPG < 140 mg/dL (7.8 mmol/L) (WHO 1985)
Interventions	Number of study centres: 5 Treatment before study: none Titration period: none
Outcomes	Composite outcome measures reported: no
Study details	Trial terminated early: yes (the trial was prematurely terminated in March 2000 by an independent end point committee, since the incidence of diabetes in the intervention group was highly significantly lower than in the control group)
Publication details	Language of publication: English Funding: commercial funding (Novo Nordisk Foundation)/non‐commercial funding (Finnish Academy, Ministry of Education, Yrjö Jahnsson Foundation, and the Finnish Diabetes Research Foundation) Publication status: peer‐reviewed journal
Stated aim of study	Quote from publication: "The aim of the Diabetes Prevention Study is to assess the efficacy of an intensive diet‐exercise programme in preventing or delaying Type II (non‐insulin‐dependent) diabetes mellitus in subjects with impaired glucose tolerance, to evaluate the effects of the intervention programme on cardiovascular risk factors and to assess the determinants for the progression to diabetes in persons with impaired glucose tolerance."
Notes	After the first screening OGTT, a repeat OGTT was carried out in participants with IGT and the mean value of the two 2‐h glucose concentrations was used as the criterion for inclusion in the study. The inclusion criteria were developed during the recruitment period but before the final criteria based on the two OGTTs were decided. After randomisation, study visits were scheduled for 1‐2 weeks, 5‐6 weeks, 3, 4 and 6 months from the beginning of the study and thereafter every 3 months. Every 3 months, 3‐d food records were completed throughout the study.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote from publication: "Subjects who enrolled in the study were randomly assigned to the intervention group or the control group by the study physician, with the use of a randomization list..." and "For the DPS and EDIPS‐Newcastle (but not SLIM) the randomisation lists were generated and supplied by the coordinating centre in Helsinki and staff who made baseline measurements had no access to the randomisation lists." Comment: adequate generation of random sequence ensured
Allocation concealment (selection bias)	Low risk	Quote from publication: "Subjects who enrolled in the study were randomly assigned to the intervention group or the control group by the study physician, with the use of a randomization list,.." and "For the DPS and EDIPS‐Newcastle (but not SLIM) the randomisation lists were generated and supplied by the coordinating centre in Helsinki and staff who made baseline measurements had no access to the randomisation lists." Comment: adequate allocation concealment ensured
Blinding of participants and personnel (performance bias) all‐cause mortality/cardiovascular mortality	Low risk	Quote from publication: "The nurses who scheduled the study visits did not have access to the randomization list. However, the staff members involved in the intervention had to be aware of the group assignment; thus, the study was only partly blinded. Laboratory staff did not know the subjects’ group assignments, and the subjects were not informed of their plasma glucose concentrations during follow‐up unless diabetes was diagnosed." Comment: investigator‐assessed outcome measure. The outcome was not likely to be influenced by lack of blinding
Blinding of participants and personnel (performance bias) incidence of T2DM	Low risk	Quote from publication: "The nurses who scheduled the study visits did not have access to the randomization list. However, the staff members involved in the intervention had to be aware of the group assignment; thus, the study was only partly blinded. Laboratory staff did not know the subjects’ group assignments, and the subjects were not informed of their plasma glucose concentrations during follow‐up unless diabetes was diagnosed." "The independent end‐points committee confirmed all newly diagnosed cases of diabetes" Comment: outcome evaluated by an independent outcome committee. Not described whether this committee was blinded. We assume that the outcome committee was blinded, however the outcome was not likely to be influenced by lack of blinding
Blinding of participants and personnel (performance bias) measures of blood glucose control	Low risk	Quote from publication: "The nurses who scheduled the study visits did not have access to the randomization list. However, the staff members involved in the intervention had to be aware of the group assignment; thus, the study was only partly blinded. Laboratory staff did not know the subjects’ group assignments, and the subjects were not informed of their plasma glucose concentrations during follow‐up unless diabetes was diagnosed." Comment: investigator‐assessed outcome measure. The outcome was not likely to be influenced by lack of blinding
Blinding of participants and personnel (performance bias) time to progression to T2DM	Low risk	Quote from publication: "The nurses who scheduled the study visits did not have access to the randomization list. However, the staff members involved in the intervention had to be aware of the group assignment; thus, the study was only partly blinded. Laboratory staff did not know the subjects’ group assignments, and the subjects were not informed of their plasma glucose concentrations during follow‐up unless diabetes was diagnosed." "The independent end‐points committee confirmed all newly diagnosed cases of diabetes" Comment: outcome evaluated by an independent outcome committee. Not described whether this committee was blinded. We assume that the outcome committee was blinded, however the outcome was not likely to be influenced by lack of blinding
Blinding of outcome assessment (detection bias) all‐cause/cardiovascular mortality	Low risk	Quote from publication: "The nurses who scheduled the study visits did not have access to the randomization list. However, the staff members involved in the intervention had to be aware of the group assignment; thus, the study was only partly blinded. Laboratory staff did not know the subjects’ group assignments, and the subjects were not informed of their plasma glucose concentrations during follow‐up unless diabetes was diagnosed." Comment: investigator‐assessed outcome measure. The outcome was not likely to be influenced by lack of blinding
Blinding of outcome assessment (detection bias) incidence of T2DM	Low risk	Quote from publication: "The nurses who scheduled the study visits did not have access to the randomization list. However, the staff members involved in the intervention had to be aware of the group assignment; thus, the study was only partly blinded. Laboratory staff did not know the subjects’ group assignments, and the subjects were not informed of their plasma glucose concentrations during follow‐up unless diabetes was diagnosed." "The independent end‐points committee confirmed all newly diagnosed cases of diabetes" Comment: outcome evaluated by an independent outcome committee. Not described whether this committee was blinded. We assume that the outcome committee was blinded, and the outcome was not likely to be influenced by lack of blinding
Blinding of outcome assessment (detection bias) measures of blood glucose control	Low risk	Quote from publication: "The nurses who scheduled the study visits did not have access to the randomization list. However, the staff members involved in the intervention had to be aware of the group assignment; thus, the study was only partly blinded. Laboratory staff did not know the subjects’ group assignments, and the subjects were not informed of their plasma glucose concentrations during follow‐up unless diabetes was diagnosed." Comment: investigator‐assessed outcome measure. The outcome was not likely to be influenced by lack of blinding
Blinding of outcome assessment (detection bias) time to progression to T2DM	Low risk	Quote from publication: "The nurses who scheduled the study visits did not have access to the randomization list. However, the staff members involved in the intervention had to be aware of the group assignment; thus, the study was only partly blinded. Laboratory staff did not know the subjects’ group assignments, and the subjects were not informed of their plasma glucose concentrations during follow‐up unless diabetes was diagnosed." "The independent end‐points committee confirmed all newly diagnosed cases of diabetes" Comment: outcome evaluated by an independent outcome committee. Not described whether this committee was blinded. We assume that the outcome committee was blinded, and the outcome was not likely to be influenced by lack of blinding
Incomplete outcome data (attrition bias) all‐cause/cardiovascular mortality	High risk	Quote from publication: "During the post‐intervention follow‐up, 36 additional participants withdrew and ten died without a verified diabetes diagnosis" Comment: participants diagnosed with T2DM not included in the mortality analyses
Incomplete outcome data (attrition bias) incidence of T2DM	Unclear risk	Quote from publication: "During the study, 40 subjects (8 percent) withdrew — 23 in the intervention group and 17 in the control group. Of these subjects, 9 could not be contacted, 3 withdrew due to severe illness, 1 died, and 27 withdrew for personal reasons." "Subjects who withdrew from the study were considered to be at risk for diabetes until their last oral glucose tolerance test, at which point data were censored." 9 yrs publication: "The last‐observation carried‐forward method was applied to all measurements for those participants who developed diabetes or who were lost to follow‐up". Quote from 9 years publication: "Altogether, 86 participants were lost to follow up without a diabetes diagnosis: 49 in the intervention group and 37 in the control group. The baseline characteristics of the dropouts were similar between the groups." Comment: inappropriate method of imputation
Incomplete outcome data (attrition bias) measures of blood glucose control	Unclear risk	Comment: not explicitly stated how many participants were included in the analyses
Incomplete outcome data (attrition bias) time to progression to T2DM	Unclear risk	Quote from publication: "During the study, 40 subjects (8 percent) withdrew — 23 in the intervention group and 17 in the control group. Of these subjects, 9 could not be contacted, 3 withdrew due to severe illness, 1 died, and 27 withdrew for personal reasons." "Subjects who withdrew from the study were considered to be at risk for diabetes until their last oral glucose tolerance test, at which point data were censored." 9 yrs publication: "The last‐observation carried‐forward method was applied to all measurements for those participants who developed diabetes or who were lost to follow‐up". and Quote from 9 years publication: "Altogether, 86 participants were lost to follow up without a diabetes diagnosis: 49 in the intervention group and 37 in the control group. The baseline characteristics of the dropouts were similar between the groups." Comment: inappropriate method of imputation
Selective reporting (reporting bias)	High risk	Comment: morbidity was described as being reported in design article, but no data available
Other bias	High risk	Comment: trial terminated early for benefit Comment: received funding from the Novo Nordisk Foundation