Outcome trial — Dulaglutide (Trulicity)
REWIND: trial summary, limitations and UK relevance
Dulaglutide reduced the risk of MACE-3 compared with placebo in adults with type 2 diabetes at high cardiovascular risk. Reported hazard ratio: ~0.88 (95% CI ~0.79–0.99), reflecting a statistically significant relative-risk reduction. REWIND is notable within the GLP-1 CVOT set for enrolling a large primary-prevention subgroup, and the benefit signal was consistent regardless of baseline atherosclerotic disease status. For the precise reported numerical results readers should consult the primary Lancet 2019 publication.
Key findings
Dulaglutide reduced the risk of MACE-3 compared with placebo in adults with type 2 diabetes at high cardiovascular risk. Reported hazard ratio: ~0.88 (95% CI ~0.79–0.99), reflecting a statistically significant relative-risk reduction. REWIND is notable within the GLP-1 CVOT set for enrolling a large primary-prevention subgroup, and the benefit signal was consistent regardless of baseline atherosclerotic disease status. For the precise reported numerical results readers should consult the primary Lancet 2019 publication.
Safety summary
GI adverse events (nausea, diarrhoea, vomiting) were more frequent with dulaglutide, consistent with the GLP-1 class profile. Acute pancreatitis events were rare and did not differ significantly between arms in the reported analyses. Rates of severe hypoglycaemia were not increased overall.
Limitations
- T2D-only population; does not establish CV benefit in obesity without diabetes.
- Individual-patient generalisability limited by trial inclusion / exclusion criteria.
- Absolute risk reduction is smaller than relative risk reduction; discussion with a prescriber is appropriate for individual application.
- Does not establish head-to-head superiority against other GLP-1 receptor agonists.
UK relevance
Long-standing UK-relevant CV-outcomes evidence for dulaglutide (Trulicity) in adults with T2D at high CV risk. Informs NICE technology-appraisal considerations and NHS prescribing pathways where CV benefit is a treatment goal.
- Does not establish CV benefit in obesity without diabetes.
- Does not establish superiority of dulaglutide over other GLP-1 receptor agonists — REWIND was placebo-controlled, not an active-comparator head-to-head trial.
- Does not prove benefit at doses or in populations outside the trial protocol.
- Does not replace individual clinical assessment; the primary-prevention subgroup finding does not translate directly to individual absolute-risk decisions.
Frequently asked questions
What did REWIND establish?
REWIND established that dulaglutide reduced the risk of MACE-3 (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) compared with placebo in adults with type 2 diabetes at high cardiovascular risk over a median follow-up of 5.4 years. The reported hazard ratio was approximately 0.88 (95% CI ~0.79–0.99). For the precise published numerical results, consult the Lancet 2019 primary publication.
Was REWIND a primary-prevention or secondary-prevention trial?
REWIND enrolled a mixed population that was substantially primary-prevention: approximately 69% of participants did not have established atherosclerotic cardiovascular disease at baseline. The CV benefit signal was consistent across subgroups regardless of baseline disease status. This distinguishes REWIND from CVOTs that enrolled predominantly secondary-prevention populations (e.g., LEADER, SUSTAIN-6).
Did REWIND include a renal outcomes signal?
A pre-specified exploratory renal composite (new macroalbuminuria, sustained decline in eGFR, or chronic renal replacement therapy) reported a favourable dulaglutide signal in REWIND. This is exploratory rather than confirmatory; the FLOW trial subsequently established renal outcomes for semaglutide in a T2D + CKD population.
How does REWIND compare to LEADER and SUSTAIN-6?
REWIND, LEADER (liraglutide) and SUSTAIN-6 (semaglutide) are the three landmark GLP-1 CVOTs in T2D. LEADER and SUSTAIN-6 enrolled predominantly secondary-prevention populations; REWIND enrolled a larger primary-prevention subgroup. Direct head-to-head cross-trial comparison is limited by protocol and population differences — the trials establish class-level CV benefit but do not rank molecules against one another.
Is REWIND relevant to NHS prescribing decisions in the UK?
Yes. REWIND is part of the evidence base MHRA and NICE considered in appraising dulaglutide (Trulicity) for T2D. It informs NHS prescribing where CV benefit is a treatment goal alongside glycaemic control. Individual prescribing decisions require appropriate clinical assessment by a qualified UK prescriber.
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Sources are tagged by class. Regulatory documents, peer-reviewed publications and trial registry records are preferred. Manufacturer disclosures and conference material are accepted where peer-reviewed publication is not yet available; preprints are flagged.
- Peer-reviewed publicationGerstein HC et al., Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND). Lancet 2019.
- Peer-reviewed publicationGerstein HC et al., Dulaglutide and renal outcomes in type 2 diabetes: an exploratory analysis of the REWIND trial. Lancet 2019.
- Regulatory document (MHRA/EMA/FDA)EMA EPAR — Trulicity
- Trial registry recordClinicalTrials.gov NCT01394952