Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial

Background

Type 2 diabetes is a chronic disorder that requires lifelong treatment. We aimed to assess whether intensive weight management within routine primary care would achieve remission of type 2 diabetes.

Methods

We did this open-label, cluster-randomised trial (DiRECT) at 49 primary care practices in Scotland and the Tyneside region of England. Practices were randomly assigned (1:1), via a computer-generated list, to provide either a weight management programme (intervention) or best-practice care by guidelines (control), with stratification for study site (Tyneside or Scotland) and practice list size (>5700 or ≤5700). Participants, carers, and research assistants who collected outcome data were aware of group allocation; however, allocation was concealed from the study statistician. We recruited individuals aged 20–65 years who had been diagnosed with type 2 diabetes within the past 6 years, had a body-mass index of 27–45 kg/m2, and were not receiving insulin. The intervention comprised withdrawal of antidiabetic and antihypertensive drugs, total diet replacement (825–853 kcal/day formula diet for 3–5 months), stepped food reintroduction (2–8 weeks), and structured support for long-term weight loss maintenance. Co-primary outcomes were weight loss of 15 kg or more, and remission of diabetes, defined as glycated haemoglobin (HbA1c) of less than 6·5% (<48 mmol/mol) after at least 2 months off all antidiabetic medications, from baseline to 12 months. These outcomes were analysed hierarchically. This trial is registered with the ISRCTN registry, number 03267836.

Findings

Between July 25, 2014, and Aug 5, 2017, we recruited 306 individuals from 49 intervention (n=23) and control (n=26) general practices; 149 participants per group comprised the intention-to-treat population. At 12 months, we recorded weight loss of 15 kg or more in 36 (24%) participants in the intervention group and no participants in the control group (p<0·0001). Diabetes remission was achieved in 68 (46%) participants in the intervention group and six (4%) participants in the control group (odds ratio 19·7, 95% CI 7·8–49·8; p<0·0001). Remission varied with weight loss in the whole study population, with achievement in none of 76 participants who gained weight, six (7%) of 89 participants who maintained 0–5 kg weight loss, 19 (34%) of 56 participants with 5–10 kg loss, 16 (57%) of 28 participants with 10–15 kg loss, and 31 (86%) of 36 participants who lost 15 kg or more. Mean bodyweight fell by 10·0 kg (SD 8·0) in the intervention group and 1·0 kg (3·7) in the control group (adjusted difference −8·8 kg, 95% CI −10·3 to −7·3; p<0·0001). Quality of life, as measured by the EuroQol 5 Dimensions visual analogue scale, improved by 7·2 points (SD 21·3) in the intervention group, and decreased by 2·9 points (15·5) in the control group (adjusted difference 6·4 points, 95% CI 2·5–10·3; p=0·0012). Nine serious adverse events were reported by seven (4%) of 157 participants in the intervention group and two were reported by two (1%) participants in the control group. Two serious adverse events (biliary colic and abdominal pain), occurring in the same participant, were deemed potentially related to the intervention. No serious adverse events led to withdrawal from the study.

Interpretation

Our findings show that, at 12 months, almost half of participants achieved remission to a non-diabetic state and off antidiabetic drugs. Remission of type 2 diabetes is a practical target for primary care.

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Diagnosing cancer in primary care

The British Journal of General Practice has published Diagnosing cancer in primary care: results from the National Cancer Diagnosis Audit. This audit shows that GPs are doing a good job at identifying patients they suspect of having cancer, and referring them in an appropriate and timely manner within five days of initial presentation. The findings highlight the usefulness of audits in taking a stocktake of where primary cancer is in cancer diagnosis across the NHS, and identifying areas for improvement moving forward.

Patient experience of primary care

Every year since 2007 the NHS in England asked patients what they think about their GP practice in a large national survey. The survey findings are intended to inform patients, healthcare professionals and planners about patients’ experience of the care provided by individual practices in England.

This National Institute for Health Research Highlight shares insights obtained from research using this general practice survey data. We share findings about what patients really think about their care, how this varies for different patient groups and how practices can act on patient feedback.

Supporting insulin initiation in type 2 diabetes in primary care: results of the Stepping Up pragmatic cluster randomised controlled clinical tria

Objective To compare the effectiveness of a novel model of care (“Stepping Up”) with usual primary care in normalising insulin initiation for type 2 diabetes, leading to improved glycated haemoglobin (HbA1c) levels.

Design Cluster randomised controlled trial.

Setting Primary care practices in Victoria, Australia, with a practice nurse and at least one consenting eligible patient (HbA1c ≥7.5% with maximal oral treatment).

Participants 266 patients with type 2 diabetes and 74 practices (mean cluster size 4 (range 1-8) patients), followed up for 12 months.

Intervention The Stepping Up model of care intervention involved theory based change in practice systems and reorientation of the roles of health professionals in the primary care diabetes team. The core components were an enhanced role for the practice nurse in leading insulin initiation and mentoring by a registered nurse with diabetes educator credentials.

Main outcome measures The primary endpoint was change in HbA1c. Secondary endpoints included the proportion of participants who transitioned to insulin, proportion who achieved target HbA1c, and a change in depressive symptoms (patient health questionnaire, PHQ-9), diabetes specific distress (problem areas in diabetes scale, PAID), and generic health status (assessment of quality of life instrument, AQoL-8D).

Results HbA1c improved in both arms, with a clinically significant between arm difference (mean difference −0.6%, 95% confidence interval −0.9% to −0.3%), favouring the intervention. At 12 months, in intervention practices, 105/151 (70%) of participants had started insulin, compared with 25/115 (22%) in control practices (odds ratio 8.3, 95% confidence interval 4.5 to 15.4, P<0.001). Target HbA1c (≤7% (53 mmol/mol)) was achieved by 54 (36%) intervention participants and 22 (19%) control participants (odds ratio 2.2, 1.2 to 4.3, P=0.02). Depressive symptoms did not worsen at 12 months (PHQ-9: −1.1 (3.5) v −0.1 (2.9), P=0.05). A statistically significant difference was found between arms in the mean change in mental health (AQoL mental component summary: 0.04 (SD 0.16) v −0.002 (0.13), mean difference 0.04 (95% confidence interval 0.002 to 0.08), P=0.04), favouring the intervention, but no significant difference in physical health (AQoL physical component summary: 0.03 (0.15) v 0.02 (0.13)) nor diabetes specific distress (5.6 (15.5) v −2.4 (15.4)). No severe hypoglycaemia events were reported.

Conclusions The Stepping Up model of care was associated with increased insulin initiation rates in primary care, and improvements in glycated haemoglobin without worsening emotional wellbeing.

Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12612001028897.

BMJ 2017;356:j783

Off-label indications for antidepressants in primary care: descriptive study of prescriptions from an indication based electronic prescribing system

Objective To examine off-label indications for antidepressants in primary care and determine the level of scientific support for off-label prescribing.

Design Descriptive study of antidepressant prescriptions written by primary care physicians using an indication based electronic prescribing system.

Setting Primary care practices in and around two major urban centres in Quebec, Canada.

Participants Patients aged 18 years or older who visited a study physician between 1 January 2003 and 30 September 2015 and were prescribed an antidepressant through the electronic prescribing system.

Main outcome measures Prevalence of off-label indications for antidepressant prescriptions by class and by individual drug. Among off-label antidepressant prescriptions, the proportion of prescriptions in each of the following categories was measured: strong evidence supporting use of the prescribed drug for the respective indication; no strong evidence for the prescribed drug but strong evidence supporting use of another drug in the same class for the indication; or no strong evidence supporting use of the prescribed drug and all other drugs in the same class for the indication.

Results 106 850 antidepressant prescriptions were written by 174 physicians for 20 920 adults. By class, tricyclic antidepressants had the highest prevalence of off-label indications (81.4%, 95% confidence interval, 77.3% to 85.5%), largely due to a high off-label prescribing rate for amitriptyline (93%, 89.6% to 95.7%). Trazodone use for insomnia was the most common off-label use for antidepressants, accounting for 26.2% (21.9% to 30.4%) of all off-label prescriptions. For only 15.9% (13.0% to 19.3%) of all off-label prescriptions, the prescribed drug had strong scientific evidence for the respective indication. For 39.6% (35.7% to 43.2%) of off-label prescriptions, the prescribed drug did not have strong evidence but another antidepressant in the same class had strong evidence for the respective indication. For the remaining 44.6% (40.2% to 49.0%) of off-label prescriptions, neither the prescribed drug nor any other drugs in the class had strong evidence for the indication.

Conclusions When primary care physicians prescribed antidepressants for off-label indications, these indications were usually not supported by strong scientific evidence, yet often another antidepressant in the same class existed that had strong evidence for the respective indication. There is an important need to generate and provide physicians with evidence on off-label antidepressant use to optimise prescribing decisions.

BMJ 2017;356:j603

The Healthy Activity Program (HAP), a lay counsellor-delivered brief psychological treatment for severe depression, in primary care in India: a randomised controlled trial

Background

Although structured psychological treatments are recommended as first-line interventions for depression, only a small fraction of people globally receive these treatments because of poor access in routine primary care. We assessed the effectiveness and cost-effectiveness of a brief psychological treatment (Healthy Activity Program [HAP]) for delivery by lay counsellors to patients with moderately severe to severe depression in primary health-care settings.

Methods

In this randomised controlled trial, we recruited participants aged 18–65 years scoring more than 14 on the Patient Health Questionnaire 9 (PHQ-9) indicating moderately severe to severe depression from ten primary health centres in Goa, India. Pregnant women or patients who needed urgent medical attention or were unable to communicate clearly were not eligible. Participants were randomly allocated (1:1) to enhanced usual care (EUC) alone or EUC combined with HAP in randomly sized blocks (block size four to six [two to four for men]), stratified by primary health centre and sex, and allocation was concealed with use of sequential numbered opaque envelopes. Physicians providing EUC were masked. Primary outcomes were depression symptom severity on the Beck Depression Inventory version II and remission from depression (PHQ-9 score of <10) at 3 months in the intention-to-treat population, assessed by masked field researchers. Secondary outcomes were disability, days unable to work, behavioural activation, suicidal thoughts or attempts, intimate partner violence, and resource use and costs of illness. We assessed serious adverse events in the per-protocol population. This trial is registered with the ISRCTN registry, number ISRCTN95149997.

Findings

Between Oct 28, 2013, and July 29, 2015, we enrolled and randomly allocated 495 participants (247 [50%] to the EUC plus HAP group [two of whom were subsequently excluded because of protocol violations] and 248 [50%] to the EUC alone group), of whom 466 (95%) completed the 3 month primary outcome assessment (230 [49%] in the EUC plus HAP group and 236 [51%] in the EUC alone group). Participants in the EUC plus HAP group had significantly lower symptom severity (Beck Depression Inventory version II in EUC plus HAP group 19·99 [SD 15·70] vs 27·52 [13·26] in EUC alone group; adjusted mean difference −7·57 [95% CI −10·27 to −4·86]; p<0·0001) and higher remission (147 [64%] of 230 had a PHQ-9 score of <10 in the HAP plus EUC group vs 91 [39%] of 236 in the EUC alone group; adjusted prevalence ratio 1·61 [1·34–1·93]) than did those in the EUC alone group. EUC plus HAP showed better results than did EUC alone for the secondary outcomes of disability (adjusted mean difference −2·73 [–4·39 to −1·06]; p=0·001), days out of work (−2·29 [–3·84 to −0·73]; p=0·004), intimate partner physical violence in women (0·53 [0·29–0·96]; p=0·04), behavioural activation (2·17 [1·34–3·00]; p<0·0001), and suicidal thoughts or attempts (0·61 [0·45–0·83]; p=0·001). The incremental cost per quality-adjusted life-year gained was $9333 (95% CI 3862–28 169; 2015 international dollars), with an 87% chance of being cost-effective in the study setting. Serious adverse events were infrequent and similar between groups (nine [4%] in the EUC plus HAP group vs ten [4%] in the EUC alone group; p=1·00).

Interpretation

HAP delivered by lay counsellors plus EUC was better than EUC alone was for patients with moderately severe to severe depression in routine primary care in Goa, India. HAP was readily accepted by this previously untreated population and was cost-effective in this setting. HAP could be a key strategy to reduce the treatment gap for depressive disorders, the leading mental health disorder worldwide.

Funding

Wellcome Trust.

Reference: The Lancet online, 14th December 2016

Counselling for Alcohol Problems (CAP), a lay counsellor-delivered brief psychological treatment for harmful drinking in men, in primary care in India: a randomised controlled trial

Background

Although structured psychological treatments are recommended as first-line interventions for harmful drinking, only a small fraction of people globally receive these treatments because of poor access in routine primary care. We assessed the effectiveness and cost-effectiveness of Counselling for Alcohol Problems (CAP), a brief psychological treatment delivered by lay counsellors to patients with harmful drinking attending routine primary health-care settings.

Methods

In this randomised controlled trial, we recruited male harmful drinkers defined by an Alcohol Use Disorders Identification Test (AUDIT) score of 12–19 who were aged 18–65 years from ten primary health centres in Goa, India. We excluded patients who needed emergency medical treatment or inpatient admission, who were unable to communicate clearly, and who were intoxicated at the time of screening. Participants were randomly allocated (1:1) by trained health assistants based at the primary health centres to enhanced usual care (EUC) alone or EUC combined with CAP, in randomly sized blocks of four to six, stratified by primary health centre, and allocation was concealed with use of sequential numbered opaque envelopes. Physicians providing EUC and those assessing outcomes were masked. Primary outcomes were remission (AUDIT score of <8) and mean daily alcohol consumed in the past 14 days, at 3 months. Secondary outcomes were the effect of drinking, disability score, days unable to work, suicide attempts, intimate partner violence, and resource use and costs of illness. Analyses were on an intention-to-treat basis. We used logistic regression analysis for remission and zero-inflated negative binomial regression analysis for alcohol consumption. We assessed serious adverse events in the per-protocol population. This trial is registered with the ISCRTN registry, number ISRCTN76465238.

Findings

Between Oct 28, 2013, and July 29, 2015, we enrolled and randomly allocated 377 participants (188 [50%] to the EUC plus CAP group and 190 [50%] to the EUC alone group [one of whom was subsequently excluded because of a protocol violation]), of whom 336 (89%) completed the 3 month primary outcome assessment (164 [87%] in the EUC plus CAP group and 172 [91%] in the EUC alone group). The proportion with remission (59 [36%] of 164 in the EUC plus CAP group vs 44 [26%] of 172 in the EUC alone group; adjusted prevalence ratio 1·50 [95% CI 1·09–2·07]; p=0·01) and the proportion abstinent in the past 14 days (68 [42%] vs 31 [18%]; adjusted odds ratio 3·00 [1·76–5·13]; p<0·0001) were significantly higher in the EUC plus CAP group than in the EUC alone group, but we noted no effect on mean daily alcohol consumed in the past 14 days among those who reported drinking in this period (37·0 g [SD 44·2] vs 31·0 g [27·8]; count ratio 1·08 [0·79–1·49]; p=0·62). We noted an effect on the percentage of days abstinent in the past 14 days (adjusted mean difference [AMD] 16·0% [8·1–24·1]; p<0·0001), but no effect on the percentage of days of heavy drinking (AMD −0·4% [–5·7 to 4·9]; p=0·88), the effect of drinking (Short Inventory of Problems score AMD–0·03 [–1·93 to 1·86]; p=0.97), disability score (WHO Disability Assessment Schedule score AMD 0·62 [–0·62 to 1·87]; p=0·32), days unable to work (no days unable to work adjusted odds ratio 1·02 [0·61–1·69]; p=0.95), suicide attempts (adjusted prevalence ratio 1·8 [–2·4 to 6·0]; p=0·25), and intimate partner violence (adjusted prevalence ratio 3·0 [–10·4 to 4·4]; p=0·57). The incremental cost per additional remission was $217 (95% CI 50–1073), with an 85% chance of being cost-effective in the study setting. We noted no significant difference in the number of serious adverse events between the two groups (six [4%] in the EUC plus CAP group vs 13 [8%] in the EUC alone group; p=0·11).

Interpretation

CAP delivered by lay counsellors plus EUC was better than EUC alone was for harmful drinkers in routine primary health-care settings, and might be cost-effective. CAP could be a key strategy to reduce the treatment gap for alcohol use disorders, one of the leading causes of the global burden among men worldwide.

Funding

Wellcome Trust.

Reference: The Lancet online 14th December 2016