Meta-analysed numbers needed to treat of novel antidiabetic drugs for cardiovascular outcomes.

Abstract

AIMS:

Absolute treatment effects-i.e. numbers needed to treat (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.

• Authors: Georg Wolff, Yingfeng Lin, Cihan Akbulut, Maximilian Brockmeyer, Claudio Parco, Alexander Hoss, Alexander Sokolowski, Ralf Westenfeld, Malte Kelm, Michael Roden, Sabrina Schlesinger, Oliver Kuss
• Journal: ESC heart failure (ESC Heart Fail) Vol. 10 Issue 1 Pg. 552-567 (Feb 2023) ISSN: 2055-5822 [Electronic] England
• PMID: 36337026 (Publication Type: Meta-Analysis, Journal Article)
• Copyright: © 2022 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

Chemical References

• Hypoglycemic Agents
• Dipeptidyl-Peptidase IV Inhibitors
• Sodium-Glucose Transporter 2 Inhibitors
• Glucagon-Like Peptide-1 Receptor

Topics

• Humans
• Hypoglycemic Agents
• Diabetes Mellitus, Type 2 (drug therapy)
• Dipeptidyl-Peptidase IV Inhibitors (therapeutic use)
• Sodium-Glucose Transporter 2 Inhibitors (therapeutic use)
• Glucagon-Like Peptide-1 Receptor (agonists, therapeutic use)
• Numbers Needed To Treat
• Cardiovascular Diseases
• Heart Failure (drug therapy)