Isca Evidence
We are one of nine research groups in the UK commissioned by the National Institute for Health and Care Research Evidence Synthesis Programme to address knowledge gaps or to answer a specific need for health, public health and social care audiences.
The other research groups are based at:
- University of Edinburgh
- University of Warwick
- University of York
- University College London (UCL)
- University of Bristol
- University of Aberdeen
- University of Glasgow
- University of Sheffield
Visit our Twitter page: https://twitter.com/IscaEvidence
**We are currently seeking people who would like to join the Patient, Carer and Public Advisory Group. Please e-mail Lauren from the PERSPEX team for more information l.asare@exeter.ac.uk**
The work
The programme of work involves appraising and synthesising research and other evidence relating to effectiveness, cost-effectiveness and patient experience across health and social care. We work closely with policy makers to make sure that our evidence syntheses address important policy and practice needs. Our outputs may include systematic reviews, qualitative evidence syntheses, rapid reviews and evidence and gap maps depending on the policy requirement and the evidence available. Where possible, we also capitalise on our substantive work to drive methods innovation.
See our current and past products below.
The Isca Evidence team
The Isca Evidence team is led by:
A core team of reviewers:
Dedicated patient and public involvement expertise:
And an extended team of researchers who provide additional specialist expertise:
Isca Evidence administrator
Isca Evidence works alongside an Expert Advisory Group who provide additional methodological and strategic guidance to support the delivery of our work. The group includes individuals from health, social care and public health backgrounds and provides valuable context and background information within the fast paced and changeable policy environment.
University press release: https://news.exeter.ac.uk/faculty-of-health-and-life-sciences/prestigious-2-5-million-award-to-fund-new-evidence-synthesis-facility-at-exeter/
PPI Community of Practice for the 9 Evidence Synthesis Groups
Isca Evidence co-leads the PPI Community of Practice for the 9 Evidence Synthesis Groups, in collaboration with Bristol ESG.
Patient and public involvement in evidence synthesis is less common and less well researched than other research methods. Many of the contributors to this emergent field of knowledge are members of the nine Evidence Synthesis Groups (ESGs). Therefore the ESGs are in a strong position to foster collaboration and expertise sharing to boost knowledge and practice of PPI in Evidence Synthesis.
To find out more about this ESG community of practice please contact Kate Boddy: k.boddy@exeter.ac.uk
Forthcoming meetings:
- 13th Feb: Elizabeth Doe, Health and Care Research Wales Evidence Centre: How we work with PPI, and how we engage with underrepresented groups
- 3rd April: presenter TBC, PPI in Confidential Reviews
- 14th May: presenter TBC, PPI in Living Network Meta-analysis
- 3rd July: presenters TBC, Public partner led topic
Current Projects
Past Projects
Key messages
- We performed an overview of the top level of evidence evaluating the effectiveness of recent weight loss drugs (GLP-1 RAs)
- Tirzepatide and semaglutide were the most effective drugs for weight loss that we looked at in this review, however there were no trials comparing tirzepatide and semaglutide 2.4 mg directly so it is not clear which of these may be better than the other.
- More evidence is needed comparing semaglutide 2.4 mg with tirzepatide, and to explore longer-term safety and effectiveness of GLP-1 RAs.
- Despite an abundance of recent high-level reviews of the evidence, their findings are inconsistent, particularly for safety outcomes, and subtle variations in methodology that influence findings may be confusing or unclear to evidence users. Furthermore, the methodological rigour of such studies should be improved.
Summary
We were tasked with providing an overview of the evidence about a series of drugs for weight loss by the UK Office for Life Sciences, which is part of both the Department for Health and Social Care, and the Department for Science, Innovation and Technology.
We looked at the most recent studies (since 2020) about the effectiveness of these drugs. We judged their scientific quality and summarised the findings of the highest quality papers.
Who?
We looked for studies of adults who are overweight or obese.
What?
This research was about a class of drugs called GLP-1 RAs or Glucagon-like peptide-1 receptor agonists. These include semaglutide (also known as Wegovy or Ozempic) and several others, which have been used mainly in management of type 2 diabetes. The drug works as an appetite suppressant by mimicking a hormone called Glucagon-like peptide-1 (GLP-1). This intestinal hormone is released after eating and typically makes people feel fuller, so should help reduce overall calorie intake.
We looked for studies called ‘network meta-analyses’ (NMAs) which have compared several of these drugs against each other, and looked at how effective they each are for weight loss. These types of studies can tell us which drugs are the most or least effective in improving weight loss.
Why?
We wanted to know whether these drugs are effective for weight loss in adults who are overweight or obese. We also wanted to know what the quality and coverage of the evidence is; this can help to identify groups of patients or doses that have been overlooked, as well as judge whether the studies are of good quality and suitably free from bias. It was also important to consider any side-effects associated with taking these drugs.
Public & Patient Involvement & Engagement (PPIE)
Over the course of 12 months PERSPEX members and researchers discussed GLP-1 RAs at 6 online meetings and through various written and video material communications. The topics discussed were spread across all three work packages of the obesity mission.The meetings highlighted safety as a key area of interest to patients and carers and contextualised the use of these drugs within a broader societal background, surfacing concerns about industry sponsorship.
PERSPEX contributed to the protocol of this review by reviewing a Plain English version. Discussion with the group highlighted safety and maintenance of weight loss as key areas of interest to patients and carers and contextualised the use of weight loss drugs within a broader societal context, with concerns about industry sponsorship. These discussions also fed into the interpretation and writing of the report.
What did we find?
We found 22 NMAs which met our criteria for inclusion. 12 NMAs investigated weight loss as a primary outcome and 3 looked at safety outcomes. 12 NMAs specifically investigated participants with type 2 diabetes and 7 specifically investigated participants with overweight or obesity.
9 NMAs included semaglutide, 11 included liraglutide, 2 included tirzepatide and 8 included exenatide. 2 NMAs included each of dulaglutide and lixisenatide. 9 reviews reported safety outcomes.
8 papers conducted analyses based on PROGRESS-PLUS criteria, a framework of criteria which identifies characteristics that influence health opportunities and outcomes. Most of these looked at ‘other personal characteristics’, such as other health conditions.
We used established tools to critically appraise the quality of the evidence found, which provides an indication of how much confidence we can place in the findings of the NMAs. These tools showed moderate confidence in most of the reviews we included. Most of the NMAs were missing data on some of the drugs we were interested in and some included poor quality studies.
Results
- Compared with placebo (an inactive substance given instead of the real drug) or usual care, all GLP-1 RAs were associated with statistically significant increased weight loss at a minimum of one time point.
- Tirzepatide and semaglutide were the most effective drugs for weight loss at higher doses, however there were no NMAs comparing tirzepatide and semaglutide 2.4 mg directly so it is not clear which of these may be better than the other.
- The drugs associated with the greatest weight loss, tirzepatide and semaglutide 2.4 mg, were generally associated with an increased risk of safety issues (adverse events (AEs), and serious adverse events (SAEs) compared to placebo. Despite these concerns, data came from a single trial, with wide confidence intervals for all outcomes indicating uncertainty about the findings.
What are the limitations of the evidence?
The types of evidence we looked for in our review are considered amongst the highest levels of evidence, but scrutiny of the studies included reveals several limitations. It was often unclear which trials were included in analyses or whether drugs were being compared directly against each other in the same trial or not. NMAs also often combined data for multiple doses of the same drug or multiple time points (e.g. 26 weeks and 52 weeks) and many NMAs were at high risk of bias. These limitations restrict our understanding and confidence in the evidence.
The majority of trials that were included in the studies we reviewed were funded by the pharmaceutical companies which make the drugs, and there may be conflicts of interest associated with this. It was fervently noted by PERSPEX, our PPIE group, that the role of industry sponsorship should be considered, particularly with respect to the possible diversion of funds and focus from societal/public health interventions to drug-based interventions.
Future research recommendations
More evidence is needed comparing semaglutide 2.4 mg with tirzepatide, and to explore longer-term safety and effectiveness. Despite an abundance of recent NMAs, findings are inconsistent, particularly for safety outcomes, and the methodological rigour of future NMAs could be improved.
Sharing our findings
- The protocol for this work is available here.
- The full report is published in the NIHR Journals Library and is available here
- A podcast discussing the project is available here
- Please note a living network meta-analysis (living NMA), a process of regularly updating the steps of an NMA to include the most current evidence, is ongoing on this topic. This is linked here
- We have also produced a briefing paper
Key messages
- We reviewed all weight loss interventions that used digital support, to see which types of digital support were associated with better outcomes.
- While no single category of digital method of supporting weight loss was effective on its own, we did find that there were 3 categories that seemed to work well and may work well together in combination - provision of information and education; contact with a specialist; and provision of incentives or rewards.
- The examples we found for these 3 categories were varied in their delivery, and it can be expected that different modes of delivery will lead to variations in effectiveness. As such, further investigation is required to determine the optimal ingredients of future weight loss programmes, which may vary between individuals.
Summary
As part of our work looking at drugs for weight loss, requested by the UK Office for Life Sciences, there was interest in how best to support patients taking the drugs of interest (i.e. GLP-1 RAs such as semaglutide, liraglutide and tirzepatide). The Office for Life Sciences wished to know how this can be done digitally. Digital support refers to support that is delivered via the internet or for example involving a phone app or computer/ tablet.
We wanted to look at studies that have used digital support with these weight loss drugs but the newness of these drugs means there is very little information published in this area. There is an abundance of research about weight loss interventions in general, and many of the existing trials use things like smartphone apps or virtual support groups, fitness trackers and online portals or information to support patients during the trial.
We looked in detail at the digital approaches used in previous weight loss programmes, to determine which types of support were linked with successful outcomes such as weight loss. We aimed to then be able to recommend a selection of digital components likely to be successful in supporting patients taking weight loss drugs in the future.
Who?
We looked for studies of adults who are overweight or obese.
What?
We looked for randomised controlled trials (RCTs) of interventions for weight loss that include digital components. Participants in the study are randomly placed in either an intervention group or a control group. The intervention group receives the package designed to achieve weight loss, be this diet and exercise, psychological intervention, fasting, weight loss drugs or anything else. Any weight loss intervention was of interest, so long as it involved a digital component.
Digital components included anything internet-based or involving a phone app or computer. We weren’t interested in telemedicine, where participants may speak to a medical professional on the phone.
We looked at the digital components, and how they have been used and grouped them into categories. We first used a technique called an intervention component analysis (ICA) to identify key common categories of the digital interventions. We looked at each included trial and noted which of these key categories were present in the trial interventions. A statistical test, called a network meta-analysis, was then used to compare the categories to find out which ones were associated with greater success (more weight loss).
Why?
We wanted to know which types of digital support are most likely to give better outcomes for patients undergoing weight loss programmes. The types of support that are frequently associated with good patient outcomes may direct our focus when developing digital support alongside prescription of weight loss drugs.
Public & Patient Involvement & Engagement (PPIE)
PERSPEX contributed substantially to this review throughout the process. Members shared their knowledge of digital support and highlighted digital exclusion and health inequalities as areas of concern. Feedback was then sought on the protocol; this led to changes to increase clarity and improve readability. PERSPEX reviewed the search strategy by reading an initial version and making suggestions for additional search terms. PERSPEX had further input on the early synthesis by reviewing the initial categories identified as part of the intervention component analysis, to describe the different ways that digital technologies were used within the included studies.
These discussions led to the addition of the ‘incentives and rewards’ category, and consideration of whether the intervention was tailored or customised in any way for participants.
What did we find?
With regards to personal characteristics related to health inequalities in the 68 studies we analysed: all 68 reported age and gender/sex of participants; 38 reported race/ethnicity; 49 reported educational attainment; 19 reported employment and four reported occupation status; 18 reported income; 5 reported a deprivation/poverty score; 2 reported socioeconomic status; and 1 reported rural residency.
A roughly equal number of studies were categorised as at low risk of bias, having some concern over risk of bias, or at high risk of bias.
Through the ICA, we identified nine categories of digital methods of support: goal setting, self-monitoring, peer support, reminders, feedback, specialist contact, information/education, competition/challenge, and incentives/rewards (see Table 1 below). These categories were delivered or facilitated by a range of digital technologies, with websites and web-based platforms, applications (i.e. for smartphones), short messaging services (SMS) and emails being the most common.
Table 1. Descriptions of digital components of interventions
| Component | Description |
|---|---|
| Self-monitoring | Participants track their own physical activity, dietary intake, or anthropometric measurements (usually weight). This was typically performed using smartphone apps linked to a fitness tracker or logging in to web-based platforms but could also be completed using emails or via online consultation. |
| Information/education | Participants receive educational information in relation to diet, exercise, weight loss or general wellbeing. Most commonly, this was provided via websites, email newsletters or videos. Participants may receive access to a source of information to sample at their leisure (e.g. website, smartphone app) or receive more structured sessions (e.g. podcasts, text messages, webinars). |
| Feedback | Participants received feedback on any aspect of the intervention, or progress towards goals. This could be delivered with a variety of media, with email and text message most common, and smartphone and web-platform messages also widely used. Message content was usually in relation to self-monitoring data and could be automated or bespoke. |
| Goal setting | Participants set goals for any intervention component or outcome, such as weight loss, physical activity, or diet, over any time-period. This was most commonly performed via smartphone apps and web-based platforms. Initial goals were usually set at the beginning of the intervention but could relate to daily, weekly, monthly or longer time points and require revisiting as necessary. |
| Reminders | Participants receive reminders to complete tasks related to the intervention, such as to log or submit data (self-monitoring), perform exercise or attend sessions. These may typically be through emails, text messages, notifications from a smartphone app or website. |
| Peer support | Peer support involved contact with other participants, intervention deliverers, nominated partners or ‘buddies’ and usually occurred via messaging services such as WhatsApp or SMS, email or social media groups like Facebook. |
| Specialist contact | Participants had contact with a trained expert, for example a dietitian, nutritionist or psychiatrist. This may have been to discuss progress, revise goals or provide education. Typically, contact was via email, chat functions or online meeting platforms such as Zoom. |
| Competition/challenge | Competitions, challenges or games were used within the intervention as extra games or to set short-term goals. Examples include step-based challenges within a smartphone app (e.g. Fitbit), hypothetical scenarios, or challenging participants to log food intake for 7 days in a row. Participants may compete with others or by themselves. |
| Incentive/reward | Digital incentives or rewards were offered either as an explicit component of the intervention or in relation to progress towards goals (e.g. virtual ‘badges’ for achievements). Incentives could be facilitated using digital means, for example a digital ‘bank’, or linked to peer support and challenges (social incentives). |
Results
- We found that no one technique or category was effective at supporting weight loss on its own and we did not find any combinations that had already been tested and found to be effective.
- We did find that there were 3 categories that seemed to work well, 3 ‘best bets’, and they may work well in combination - provision of information and education; contact with a specialist; and provision of incentives or rewards.
What are the limitations of the evidence?
As anticipated, we did not identify any relevant studies using digital approaches to support patients using specific weight loss drugs. As such, the applicability of our findings in this context is limited. However, our statistical tests suggest that different studies found similar results for the same outcomes. We can be reassured that consistencies in patient experiences and behaviours across weight loss interventions should mean our findings can translate to patients using weight loss drugs, especially as they should be prescribed alongside changes to diet and exercise.
Future research recommendations
- Research the combination of the 3 ‘best bets’ we found.
- Our research captured the presence of a category, not its nature (i.e. frequency, intensity etc). The examples we found for each ‘best bet’ category were varied in their delivery, and it can be expected that different modes of delivery will lead to variations in effectiveness. As such, further investigation is required to determine the optimal ingredients of future weight loss programmes, which may vary between individuals.
- Many of the included trials imposed an upper limit of 39.9 kg/m2 for body mass index (BMI) for inclusion into the study (the upper range for patients living with obesity class 2). Therefore, the needs of patients living with obesity class 3 are not well represented in the current research and need to be included in future research.
Sharing our findings
- The protocol for this work is hosted on PROSPERO with the ID CRD42023493254, available here
- The academic paper is published in the Journal of Medical Internet Research, and is available here
- A podcast discussing the project is available here
- A blog post discussing this work in the context of the government's 10 year plan is available here
- We have also produced a briefing paper
Key messages
- We were tasked with finding all evidence about the views of people who have taken, prescribed or supported a patient with taking weight loss drugs (GLP-1 RAs)
- Researchers have spoken directly with patients/public, healthcare professionals, both patients/public and healthcare professionals, and looked at social media interactions. None have spoken directly to carers of people using specific weight loss drugs such as semaglutide (GLP-1 RAs)
- Until a more complete understanding of patient, carer and clinician experiences is obtained, some caution should be applied to the commissioning of services supporting the delivery of GLP-1 RAs.
Summary
We were tasked with finding out about the views and experiences of people who use weight loss drugs, and those of the family or carers who support them, called Glucagon-like peptide-1 receptor agonists (GLP-1 RAs). Examples include semaglutide (also known as Ozempic or Wegovy) and liraglutide.
Who?
We looked for studies of anyone who has taken, prescribed or supported people with taking GLP-1 RAs for any indication.
What?
We looked in online libraries for research based on interviews, focus groups, social media posts or surveys with open questions with patients, carers, family members or clinicians who have experience of:
- Being prescribed GLP-1 RAs;
- Supporting someone prescribed GLP-1 RAs;
- Prescribing GLP-1 RAs;
- Supporting access to, or services delivering, GLP-1 RAs
GLP-1 RAs could have been prescribed:
- For any reasons;
- To people of any age;
- Within health or community settings
We then brought together the views and experiences of all participants across all of the included studies.
We considered how the findings could inform future policy, research and clinical practice.
Why?
We wanted to gather insights into people’s experiences of taking or supporting others to take GLP-1 RAs, to help understand issues which may affect their long-term use, safety and acceptability, and inform UK government policy.
Public & Patient Involvement & Engagement (PPIE)
In this review, PERPSEX checked the initial search strategy and made suggestions for additional search terms. A plain English version of the draft protocol was sent to members to read prior to the June 2024 online PERSPEX meeting. This document informed discussions about the review, particularly the included population, and whether this should include only those prescribed GLP-1 RAs or those taking them through other means. This directly informed development of the review protocol.
What did we find?
Of the 25 studies that met our inclusion criteria: 11 gathered the views of patients; 4 with healthcare professionals (HCPs) or clinicians; 3 spoke to both patients/public and healthcare workers; and 7 were social media based.
Most studies collected data through interviews with some additionally using focus groups, a survey or observation of GP consultations.
Of 7 studies interviewing HCPs, 6 discussed prescribing or stopping prescribing GLP-1 RAs. Of 14 studies speaking to patients/public, 8 discussed taking GLP-1 RAs as a prescription, 3 discussed purchasing or choosing GLP-1 RAs, two investigated experiences of taking the drug within a trial, and 1 was specific to taking semaglutide as part of a specialist paid weight management intervention.
Key observations
- The studies discussing prescribing and deprescribing of GLP-1 RAs by healthcare professionals highlighted some of the complexities, practicalities and costs involved in prescribing the medications and the considerations for adverse events.
- Studies investigating the purchasing or choosing of GLP-1 RAs by patients or the public discussed factors, thoughts and preferences in identifying reasons for choosing GLP-1 RAs medication.
- Some of the common themes identified around patient views included: treatment practicalities, the want for an easy simple regime, routes of administration (taking the drug as a tablet or injection), treatment adherence and satisfaction, side effects, the need for ongoing support, and social and emotional factors.
- Studies focussing on social media highlighted strong public interest in GLP-1 RAs and raised discussion points around public perceptions or experiences of use, however, the origin of social media posts and therefore the context of drug use was unclear.
- There was no evidence about the views, experiences or perceptions of carers regarding the use of GLP-1 RAs.
What are the limitations of the evidence?
This review was limited by the quantity and quality of primary qualitative research (such as interviews) exploring patient, clinician and especially carer experiences of using of GLP-1 RAs for any indication and especially for weight loss. There were limitations with data collection and data analysis techniques in the included studies, with often a limited focus on GLP-1-RAs, reducing the value of in-depth interpretation of findings. The lack of transparency around the potential impact of conflicts-of-interest on the findings is a further limitation with this body of evidence to date.
Future research recommendations
- There is an urgent need for high-quality qualitative evidence to explore the experiences of patients, carers and clinicians with respect to the use of GLP-1 RAs, particularly those indicated for weight loss. This type of qualitative evidence is crucial to facilitate decision making, understand patients’, carers’ and clinicians’ support needs, and inform service development.
- Qualitative evaluations could be conducted alongside new randomised controlled trials, or as stand-alone studies seeking to recruit a diverse range of participants. Qualitative methods that elicit rich experience data would be particularly valuable.
- Until a more complete understanding of patient, carer and clinician experiences’ is obtained, some caution should be applied to the commissioning of services supporting the delivery of GLP-1 RAs.
Sharing our findings
- The protocol for this work is registered on Zenodo
- The academic paper is published by Health Expectations and is available here
- A podcast discussing the project is available here
- We have also produced a briefing paper
Key messages
- We found a relatively small amount of evidence on the effectiveness and cost-effectiveness of osteoporosis screening in postmenopausal women.
- None of our included studies assessed the effectiveness of targeted screening for women with risk factors for osteoporosis.
- Most of the available evidence does not consider the impact of health inequalities.
- More research is needed to help policymakers make decisions about screening.
Summary
We were tasked with finding the current evidence on whether screening women for osteoporosis helps precent fractures, compared to their usual care.
Who?
We focussed on two groups of women, those over 65 and those under 65 with risk factors for osteoporosis. We were also interested in whether screening provides good value for money and whether health inequalities have been considered
What?
This research is about screening for osteoporosis, a bone disease which causes bones to become weak and fragile and lead to fractures happening more easily. Osteoporosis is most common in women who have gone through the menopause (postmenopausal). Osteoporosis screening is the process of identifying people with an increased risk of osteoporosis by using risk assessment tools or medical imaging. We looked for research studies that had compared the impact of a screening programme for osteoporosis with usual clinical care.
Why?
We wanted to know how much evidence there is that can help policymakers decide whether to offer screening for osteoporosis to postmenopausal women.
Public & Patient Involvement & Engagement (PPIE)
In this review, PERPSEX members discussed the research question at online meetings in October and November 2024. Members felt that the screening for osteoporosis was relevant for other populations as well as postmenopausal women. They were also highlighted the potential for screening harms as an area of interest. These discussions informed the development of the protocol.
What did we find?
We found 19 studies about screening for osteoporosis in postmenopausal women including four clinical studies and six reviews. The studies looked at different screening methods and generally included all women over 65 rather than looking at younger women with risk factors for osteoporosis. Studies reported outcomes including fractures, quality of life and cost-effectiveness of screening, and some considered health inequalities.
Limitations
We were only interested in studies that compared the effectiveness of screening with usual clinical care, therefore studies that compared different methods of screening were excluded.
Future research recommendations
- No new studies have been published since 2018. More high-quality research particularly n targeted screening for women with risk factors for osteoporosis is therefore needed to inform decision-making in this area.
- Existing reviews draw most of their evidence for the effectiveness of screening from the same few studies; further evidence synthesis is unlikely to be helpful until new studies have been conducted.
- Future research should consider the potential harms of screening.
- Health equity indicators should be considered and analysed in future research to ensure that decisions around screening for osteoporosis are equitable.
Sharing our findings
- The protocol for this work is registered on Zenodo.
- This report has been submitted to the NIHR Journals Library and will be available here when published.
