DiRECT has a realistic or ‘pragmatic’ design to provide information about the management of type 2 diabetes in a routine primary care setting in a largely unselected population in order to maximise transferability of results. Certain inclusion criteria were applied for recruitment into DiRECT for various practical reasons. An upper BMI limit of 45 kg/m2 was set because the protocol required a subsample to undergo abdominal magnetic resonance imaging. An upper age limit of 65 years was fixed to avoid the greater mortality rates associated with older people in a study planned to continue for 2 years and to optimise attendance at study visits given the greater mobility problems often faced by older people with type 2 diabetes. Furthermore, individuals were excluded if they had suffered myocardial infarction or stroke within the 6 months prior to recruitment because of engagement in other programmes.
Volunteers for clinical research are usually relatively more health conscious and there can be a risk of attracting unrepresentative ‘concerned but healthy’ individuals. The DiRECT cohort included, at baseline, 12% with existing retinopathy, 12% with one or more known manifestations of heart disease and 13% with microalbuminuria indicating nephropathy. Impaired renal function (eGFR <60) was present in 3%. In addition to their diabetes, as may be expected, a high proportion (57%) had known hypertension and 31% were prescribed two or more antihypertensive medications. Polypharmacy was common, with 43% being prescribed six or more different drugs daily and 13% prescribed ten or more drugs. Almost a quarter of the entire cohort was prescribed antidepressant medications, some of which are associated with weight gain . Thus, the DiRECT cohort does not appear to include an excess of ‘worried well’ or unusually healthy people with type 2 diabetes.
DiRECT recruited a substantial proportion of men. This is encouraging as this is in line with the higher prevalence of type 2 diabetes in men . Comparison of the study population with available data for those invited to participate in DiRECT shows an almost identical proportion of men and women accepting the invitation to participate (Table 5). Typically, men are less likely to engage in weight management programmes [13,14,15]. However, the potential for health improvement is a motivator for weight loss in men [16, 17], so a potential remission of diabetes or improvement in diabetes status may have encouraged men to participate in DiRECT. Whether a total diet replacement approach might be more attractive to men than to women, and other motivational issues, will be explored in interviews with participants and with healthcare professionals involved in DiRECT.
Recruitment of participants to any study is challenging. Poor recruitment can result in inadequate study numbers and underpowered trials . DiRECT was based in primary care in order to provide realistic results transferable to routine practice. Of the invited practices, 14% accepted, reflecting the relatively small proportion of general practices in the UK that are research-active. Many of those are at capacity for taking on new research projects, being busy NHS general practices with limited availability of doctor and nurse time for research. There was great interest in DiRECT, but many of the research-active practices had already committed to research studies on other topics. Moreover, practice participation required practices to be able to provide six to ten individuals who would meet the inclusion criteria; this excluded some smaller practices. Recruitment to DiRECT was monitored closely and recruitment methods were refined to include strategies known to maximise recruitment (e.g. reminder letter, telephone contact and incentive) . It is remarkable that 28% of all invited to participate expressed interest in doing so, and most of those who initially volunteered participated (72%). This far exceeds many other trials that recruited using similar methods  and those that recruited by other means [20, 21]. The study recruited more than the numbers required to satisfy the a priori power calculation (140 per group) within the 2 years allocated for recruitment, and recruitment proved difficult to halt resulting in modest over-recruitment. The ready acceptance of a low-energy liquid diet has been observed in all of our previous studies [1, 3, 9].
Triacylglycerol, insulin, fasting glucose and eGFR were less good in Scottish participants, in keeping with the slightly greater age and higher waist circumferences. None of these differences could be considered clinically important. Average alanine aminotransferase (ALT) and γ-glutamyl transferase (GGT) levels were higher than the normal reference range. There were a small number with ALT and GGT raised more so than aspartate aminotransferase (AST). This will be partly the result of fatty liver, which is common in this participant group, but more substantial elevations in GGT without comparable ALT elevations suggest that some participants may have had undisclosed alcohol excess. Of the 12 participants with GGT >150 at baseline, only one reported very high alcohol consumption (72 units per week). In most instances transaminases were also elevated but there were no other features in the baseline data which might account for abnormal liver function tests. There were minor excesses of high albumin/creatinine ratio (ACR) in Tyneside, the reasons for which were not clear although the numbers are small and do not allow determination of whether such minor albuminuria was sustained or transient.
The participants can be considered representative of the general population of people with short duration type 2 diabetes, and their characteristics were similar to those of other large studies of type 2 diabetes (Table 6). Comparison with LookAHEAD  showed similar mean HbA1c (55 mmol/mol [7.2%]) and BMI (35.9 kg/m2), low prevalence of CVD (14.1%) and a high proportion of participants never having smoked (50.2%), although the proportion of male participants was lower (40%) and the population slightly older. The prevalence of CVD was higher in the ACCORD  and PROactive  studies, but this was a specific inclusion criterion for both those studies. As in DiRECT, both of these studies had high proportions of male participants and a similar mean BMI. Median HbA1c was higher in ACCORD and PROactive (64 mmol/mol [8%]). Importantly, duration of diabetes was longer in all three of these previous studies, while it was specifically limited to <6 years in the present study. This duration was selected in view of the demonstration of duration of type 2 diabetes being a critical factor in achieving remission . Our study population was, however, very representative of all people with type 2 diabetes in Scotland, in whom the mean duration of diabetes was 9 years . A greater number of medications were prescribed to the Scottish than to the Tyneside participants, perhaps reflecting variations in the application of the different clinical guidelines in Scotland  and England .
A remarkably high proportion of eligible people with type 2 diabetes volunteered to enter DiRECT, including more men than is usual for weight management trials. The participants recruited were broadly representative of the unselected general population of people with up to 6 years’ duration of type 2 diabetes, and the subset in Tyneside were similar to the Scottish subset. The recruitment rates into the intervention and control arms were almost identical. The results of the weight management intervention in DiRECT are thus likely to be widely applicable to people with type 2 diabetes.