Meta-analysis of 13 studies with 96,860 patients shows Meta-NNTs for cardiovascular mortality of 178 for DPP-4 inhibitors, 261 for GLP-1 receptor agonists, and 118 for SGLT2 inhibitors.
Thirteen studies reported modest treatment benefits of GLP-1 receptor agonists and SGLT2 inhibitors for cardiovascular mortality in primary type 2 diabetes populations.
DPP-4 inhibitors showed a Meta- of 178, while GLP-1 receptor agonists had a Meta-NNT of 261, indicating relative treatment effects.
SGLT2 inhibitors demonstrated a lower Meta-NNT of 118 for cardiovascular mortality compared to other drug classes.
For hospitalization due to heart failure, ten studies analyzed 96,128 patients, revealing a Meta-NNT of -644 for DPP-4 inhibitors and 441 for GLP-1 receptor agonists.
SGLT2 inhibitors were particularly effective in primary heart failure populations, showing a Meta-NNT of 25, compared to 233 in primary diabetes populations.
Simplified
AIMS: Absolute treatment effects-i.e. (NNTs)-of novel antidiabetic drugs for cardiovascular outcomes have not been comprehensively evaluated. We aimed to perform a meta-analysis of digitalized individual patient outcomes to display and compare absolute treatment effects.
METHODS AND RESULTS: Individual patient time-to-event information from Kaplan-Meier plots of cardiovascular mortality (CM) and/or hospitalization for heart failure (HHF) endpoints from cardiovascular outcome trials (CVOTs) evaluating dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium glucose transporter 2 (SGLT2) inhibitors vs. placebo were digitalized using WebPlotDigitizer 4.2 and the R code of Guyot et al.; Weibull regression models were generated, validated, and used to estimate NNT for individual trials; random-effects meta-analysis generated Meta-NNT with 95% confidence intervals. Sixteen CVOTs reported time-to-event information (14 in primary diabetes and 2 in primary heart failure populations). Thirteen studies including 96 860 patients were meta-analysed for CM: At the median follow-up of 30 months, Meta-NNTs were 178 (64 to ∞ to -223) for DPP-4 inhibitors, 261 (158 to 745) for GLP-1 receptor agonists, and 118 (68 to 435) for SGLT2 inhibitors. Ten studies including 96 128 patients were meta-analysed for HHF: At the median follow-up of 29 months, estimated Meta-NNTs were -644 (229 to ∞ to -134) for DPP-4 inhibitors, 441 (184 to ∞ to -1100) for GLP-1 receptor agonists, and 126 (91 to 208) for SGLT2 inhibitors. SGLT2 inhibitors were especially effective for HHF in primary heart failure populations [Meta-NNT 25 (19 to 39)] vs. primary diabetes populations [Meta-NNT 233 (167 to 385)] at 16 months of follow-up.
CONCLUSIONS: We found only modest treatment benefits of GLP-1 receptor agonists and SGLT2 inhibitors for CM and HHF in primary type 2 diabetes mellitus populations. In primary heart failure populations, SGLT2 inhibitor benefits were substantial and comparable in efficacy to established heart failure medication.
Key numbers
118
Meta- for cardiovascular mortality
At a median follow-up of 30 months for SGLT2 inhibitors.
126
Meta- for hospitalization for heart failure
At a median follow-up of 29 months for SGLT2 inhibitors.
25
Meta- for primary heart failure populations
At 16 months of follow-up for SGLT2 inhibitors.
Full Text
We can’t show the full text here under this license.
All authors declare that there was no financial or other support from any industry or third party for the submitted work. Unrelated to this work, OK received honoraria for biostatistical education from Berlin‐Chemie. MR received personal fees from Allergan, AstraZeneca, Bristol Myers Squibb, Eli Lilly, Fishawack Group, Gilead Sciences, Intercept Pharma, Inventiva, Novartis, Novo Nordisk, Pfizer, ProSciento, Sanofi US, and Target RWE and investigator‐initiated research support from Boehringer‐Ingelheim, Nutricia/Danone, and Sanofi‐Aventis.
