Indirect comparison of glucagon like peptide-1 receptor agonists regarding cardiovascular safety and mortality in patients with type 2 diabetes mellitus: network meta-analysis

Abstract

Background: The cardiovascular outcome trials (CVOTs) have shown that glucagon like peptide-1 receptor agonists (GLP1RAs) have varying degrees of cardiovascular (CV) safety in patients with type 2 diabetes mellitus (T2DM.) The lack of any head-to-head comparative trials among GLP1RAs urged the need for an indirect comparison of these agents. Therefore, this study was conducted to indirectly compare the CV safety and mortality effects among different GLP1RAs in patients with T2DM using network meta-analysis (NMA). Methods: Medline was searched to identify GLP1RA CVOTs to date. The outcomes of interest were CV death, myocardial infarction (IM), stroke, and death from any cause. An NMA with binomial likelihood logit link model was used for the binary outcomes. We conducted both fixed effects and random effects models for each outcome, and selected the best model based on the deviance information and the average posterior residual deviance. This NMA was reported in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA-NMA). Results: A total of seven GLP1RA CVOTs were included having 56,004 patients. The NMA results showed that oral semaglutide was statistically better than exenatide (OR 0.47, 95% CI 0.21-0.99), dulaglutide (OR 0.46, 95% CI 0.20-0.97), albiglutide (OR 0.45, 95% CI 0.19-0.97), lixisenatide (OR 0.43, 95% CI 0.19-0.92) in reducing CV death events. No significant differences were detected between most of the treatments regarding reducing death from any cause, MI and stroke events. The ranking results showed that oral semaglutide had the highest probability to be ranked first (> 90%) in reducing CV death and death from any cause. Moreover, once weekly semaglutide had the highest probability to be ranked first in reducing MI and stroke events. Conclusion: The GLP1RAs have shown significant benefits in terms of CV safety. The indirect comparison and ranking probability results have shown that one weekly semaglutide and oral semaglutide seems to be the preferred option in patients with T2DM and established or at high risk of CVD. This result can aid health care providers, pharmacy and therapeutics committees in hospitals, and insurance companies when deciding which GLP1RA to start or add to their formulary.

Comparative effectiveness of dulaglutide versus liraglutide in Asian type 2 diabetes patients: a multi-institutional cohort study and meta-analysis

“…Second, the present study only assessed the clinical effectiveness of GLP-1RAs in terms of short-term clinical biochemical marker changes (e.g., HbA1c, eGFR), while the hard endpoints of treatments (e.g., cardiovascular disease, death, progression to end-stage renal disease) were not measured. To date, there is a lack of direct head-to-head comparative trials of GLP-1RAs on the long-term cardiovascular safety and mortality, but there are indirect comparisons from three network meta-analysis studies [ 42 – 44 ]. This suggests that future studies with the long-term follow-up period on hard outcomes among GLP-1RAs are needed.…”

Comparative effectiveness of dulaglutide versus liraglutide in Asian type 2 diabetes patients: a multi-institutional cohort study and meta-analysis

“…Second, the present study only assessed the clinical effectiveness of GLP-1RAs in terms of short-term clinical biochemical marker changes (e.g., HbA1c, eGFR), while the hard endpoints of treatments (e.g., cardiovascular disease, death, progression to end-stage renal disease) were not measured. To date, there is a lack of direct head-to-head comparative trials of GLP-1RAs on the longterm cardiovascular safety and mortality, but there are indirect comparisons from three network metaanalysis studies [44][45][46]. This suggests that future studies with the long-term follow-up period on hard outcomes among GLP-1RAs are needed.…”

Semaglutide for the Management of type 2 Diabetes: Clinical Evidence, Cardioprotective Effects, and Guidelines

“…Попытка подобного сравнения по данным опубликованных рандомизированных исследований была выполнена О. М. Alfayez и соавт. [54]. Согласно полученным результатам, пероральный семаглутид превосходил эксенатид длительного действия (ОР 0,47; 95 % ДИ от 0,21 до 0,99), дулаглутид (ОР 0,46; 95 % ДИ от 0,2 до 0,97), албиглутид (ОР 0,45; 95 % ДИ от 0,19 до 0,97) и ликсисенатид (ОР 0,43; 95 % ДИ от 0,19 до 0,92), но не инъекционную форму семаглутида (ОР 0,44; 95 % ДИ от 0,18 до 1,03) в отношении снижения риска смерти от ССЗ.…”

“…Согласно полученным результатам, пероральный семаглутид превосходил эксенатид длительного действия (ОР 0,47; 95 % ДИ от 0,21 до 0,99), дулаглутид (ОР 0,46; 95 % ДИ от 0,2 до 0,97), албиглутид (ОР 0,45; 95 % ДИ от 0,19 до 0,97) и ликсисенатид (ОР 0,43; 95 % ДИ от 0,19 до 0,92), но не инъекционную форму семаглутида (ОР 0,44; 95 % ДИ от 0,18 до 1,03) в отношении снижения риска смерти от ССЗ. Влияние препаратов на смертность от всех причин оказывалось сопоставимым, тогда как преимущества в отношении профилактики инсульта и ИМ, возможно, имел инъекционный семаглутид [54]. Безусловно, к полученным результатам следует относиться с большой осторожностью ввиду существенных ограничений, связанных с методами сравнения данных в этом исследовании.…”