Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and cancer prevention through weight loss: emulating a target trial and mediation analysis
Closing date: 17/11/2025
Leeds-Manchester Clinical Research Training Fellowship: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and cancer prevention through weight loss: emulating a target trial and mediation analysis
Lead Supervisors: Prof. Andrew Renehan
Co-Supervisors: Dr Duncan Wilson, Prof. Michelle Harvie, Prof. Matt Sperrin, Prof. Darren Ashcroft, Prof. Sam Smith, Associate Prof. Michelle Collinson, Mr Matthew Harris
Applications Deadline: 12:00pm Monday 17th November 2025
Interviews: Week commencing 12th January 2026
Start date: September 2026
Project Keywords: Obesity; GLP-1 agonists; cancer prevention
Research Opportunity: Leeds-Manchester Clinical Research Training Fellowship leading to the award of PhD
Project Outline
Obesity is causally associated with increased risk of at least 13 adult cancer types and is the second commonest cause of cancer. Whether intentional weight loss leads to reduced cancer risk is a major research gap and CRUK are seeking policy-relevant evidence.
PADRAIC: The MCRC Leeds-Manchester Collaborative currently funds the PADRAIC PhD thesis (completion: March 2026), which focuses on simulating weight loss interventions and cancer prevention. Through systematic reviews; international consensus meetings; and in-silico Bayesian modelling, this prize-winning thesis established: (i) glucagon-like peptide-1 receptor agonists (GLP-1RAs), anti-diabetes drugs recently shown to cause substantial weight loss, are the front runners for weight-losing interventions; (ii) a pragmatic design, such as a target cohort trial design, is favoured due to the rapidly changing field.
Aim: To emulate a target trial within a high-quality population-based database with GLP-1RAs prescription and dosage data e.g. UK Clinical Practice Research Datalink (CPRD), through an internationally recognised established stepwise framework. A novel ‘added value’ in this thesis will be mediation analyses to investigate whether GLP-1RAs reduce cancer risk directly (e.g. on tumour biology) or indirectly through sustained weight loss.
Research plan (Workstreams, WSs): WS1: Use data from PADRAIC and international expert network to agree a theoretical trial protocol; WS2: Use CPRD to harvest data on the use of GLP-1RAs in patients with and without diabetes, and determine the quality of confounding data; WS3: Perform a mediation analysis in the SELECT trial (N: 18,000 overweight/obese individuals) to differentiate the direct and indirect effects through weight loss of the GLP-1RA Semaglutide. And perform a parallel mediation analysis in the LookAHEAD trial (intensive lifestyle intervention, FU > 10 years) as the ‘positive control’ to demonstrate that weight loss leads to cancer prevention; WS4: Complete the target trial emulation with longitudinal matching and analyses to reduce immortal time and risk susceptibility biases.
Applications for this project are now open. Please complete your application on The University of Manchester website.
About Prof. Andrew Renehan (project Lead Supervisor)
Andrew Renehan is Professor of Cancer Studies and Surgery and leads the Manchester Cancer Research Centre (MCRC) Diabesity and Cancer Research Group, studying relationships between obesity, diabetes, and anti-diabetes therapies, with cancer risk and outcomes – including clinical epidemiology and translational studies. This group is located within the Cancer Screening and Prevention hub at the MCRC Kinnaird Road site and at the Farr Institute@HeRC at Vaughan House on the main University campus. At any one time, he has a team of 1 to 2 postgraduate fellows and 3 to 4 students working on projects in this theme.
Key information
Before submitting an application, please ensure you have read the information below about the funding arrangements and eligibility for our Clinical Research Training Fellowships.
We also encourage you to get in contact with the lead supervisor to discuss the project and any particulars.
Further information is available on the Clinical Research Training Fellowships webpage.
The clinical fellowships are usually tenable for three years, although in certain circumstances they may be four years duration. The Fellowship covers:
- running expenses,
- an appropriate salary in line with the applicant’s current salary and grade
- full coverage of University PhD fees at the UK/home fee rate.
International Candidates
The University of Manchester aims to support the most outstanding applicants from outside the UK.
We are able to offer a limited number of bursaries to high-performing EU and international candidates, covering PhD fees only. Bursaries do not include financial support for visa/health surcharges.
We assess each EU and international candidate’s suitability for a bursary at the application and interview stages.
You must be a post-registration clinician, and ideally have a specialist post in a related subject, to apply for our Clinical Research Training Fellowships.
Applicants must hold an MBChB degree or an equivalent medical qualification. You should also hold, or be about to obtain, a minimum upper second class (or equivalent) undergraduate degree in a relevant subject. A related master’s degree would be an advantage.
It is generally expected that CRTFs will return to a training programme in the UK upon completion of their research degree.
International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) before contacting potential supervisors to express an interest in their project. Eligibility information can be found on the University’s Country Specific information page.
Applications for this programme are now open. Please submit your application on The University of Manchester application portal.
Key dates
- Applications open: Monday 6th October 2025
- Application deadline: 12:00pm Monday 17th November 2025
- Interviews: Week commencing 12th January 2026
- Start date: September 2026
Useful Links
Submit your application
Interested in applying for this opportunity? Submit your application on The University of Manchester application portal.
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