Department of Family Medicine, University of Toledo College of Medicine, Ohio robert.gotfried@utoledo.edu
The authors reported no potential conflict of interest relevant to this article.
The author has lectured on behalf of Pfizer and Kos/Abbott. He has participated in clinical trials for Bristol-Myers Squibb, Novo Nordisk, AstraZeneca, KOS/Abbott, Novartis, and Janssen. He has wholly declined compensation from pharmaceutical and medical device manufacturers.
REWIND. The Researching Cardiovascular Events with a Weekly INcretin in Diabetes trial (REWIND),20 the most recently completed GLP-1 receptor agonist CVOT (presented at the 2019 American Diabetes Association [ADA] Conference in June and published simultaneously in The Lancet), was a multicenter, randomized, double-blind placebo-controlled trial designed to assess the effect of weekly dulaglutide, 1.5 mg, compared with placebo, in 9901 participants enrolled at 371 sites in 24 countries. Mean patient age was 66.2 years, with women constituting 4589 (46.3%) of participants.
REWIND was distinct from other CVOTs in several ways:
Other CVOTs were designed to show noninferiority compared with placebo regarding CV events; REWIND was designed to establish superiority
In contrast to trials of other GLP-1 receptor agonists, in which most patients had established CV disease, only 31% of REWIND participants had a history of CV disease or a prior CV event (although 69% did have CV risk factors without underlying disease)
REWIND was much longer (median follow-up, 5.4 years) than other GLP-1 receptor agonist trials (median follow-up, 1.5 to 3.8 years).
In REWIND, the primary composite outcome of MACE-3 occurred in 12% of participants assigned to dulaglutide, compared with 13.1% assigned to placebo (P = .026). This equated to 2.4 events for every 100 person– years on dulaglutide, compared with 2.7 events for every 100 person–years on placebo. There was a consistent effect on all MACE-3 components, although the greatest reductions were observed in nonfatal stroke (P = .017). Overall risk reduction was the same for primary and secondary prevention cohorts (P = .97), as well as in patients with either an HbA1c value < 7.2% or ≥ 7.2% (P = .75). Risk reduction was consistent across age, sex, duration of T2D, and body mass index.
Dulaglutide did not significantly affect the incidence of all-cause mortality, heart failure, revascularization, or hospital admission. Forty-seven percent of patients taking dulaglutide reported gastrointestinal adverse effects (P = .0001).
Cases of bullous pemphigoid have been reported after initiation of DPP-4 inhibitor therapy.
In a separate analysis of secondary outcomes, 21 dulaglutide reduced the composite renal outcomes of new-onset macroalbuminuria (P = .0001); decline of ≥ 30% in the estimated glomerular filtration rate (P = .066); and chronic renal replacement therapy (P = .39). Investigators estimated that 1 composite renal outcome event would be prevented for every 31 patients treated with dulaglutide for a median 5.4 years.
