Adding dulaglutide only slightly decreases major adverse CV events in patients with T2DM and CVD risk factors (REWIND)

Référence

Gerstein HC, Colhoun HM, Dagenais GR, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet 2019;394(10193):121-130.

Sommaire

The Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial was conducted at 371 sites in 24 countries. The researchers recruited patients older than 50 years with type 2 diabetes and hemoglobin A1C levels less than 9.5% on stable doses of up to 2 oral agents with or without basal insulin. All patients also had existing vascular disease, with the following exceptions: Patients older than 55 years could be included if they had subclinical vascular disease, and those older than 60 years could be included if they had 2 or more traditional CVD risk factors. All patients went through a 3-week run-in period during which they received placebo and learned how to inject the study drug. Since the study only included patients who were 100% compliant with the placebo injections, more than 1000 patients were excluded after the run-in period. This limits applicability to patients like ours who are not always 100% adherent to therapy. The researchers then added either weekly subcutaneous injections of dulaglutide 1.5 mg (n = 4949) or placebo (n = 4952). The researchers evaluated the patients at 2 weeks, 3 months, and 6 months, and then every 3 months for drug dispensing and every 6 months for detailed assessments. They used intention-to-treat analysis to evaluate the time to the first MACE (nonfatal myocardial infarction, nonfatal stroke, and death from cardiovascular causes or unknown causes). They also had many secondary outcomes, raising the concern about some "benefits" occurring due to chance alone. (I searched Clinicaltrials.gov and could not find the authors' analytic plans beyond describing their outcome measures.) The median duration of diabetes was 9.5 years and the median hemoglobin A1C level was 7.2%. After a median follow up of 5.4 years (51,820 person-years), slightly more than 70% of patients were taking the study drug at the last visit. More participants who were taking dulaglutide (9.1%) than placebo (6.3%) permanently stopped treatment because of an adverse event (number needed to treat to harm [NNTH] = 36; 95% CI 26 - 56). Fewer participants who were taking dulaglutide had a MACE (12.0%; 2.4 per 100 person-years) than those taking placebo (13.4%; 2.7 per 100 person-years; number needed to treat = 73; 38 - 1347). The authors report no meaningful variances from the main findings among multiple subgroups of patients. The most common adverse event, gastrointestinal upset, was more common in dulaglutide-treated patients (47.4%) than in placebo-treated patients (34.1%; NNTH = 8; 7 - 9). At Goodrx.com, one month of dulaglutide (with a discount) costs more than $650.