Efficacy of antihyperglycemic therapies on cardiovascular and heart failure outcomes: an updated meta-analysis and meta-regression analysis of 35 randomized cardiovascular outcome trials
An erratum to this article was published (Cardiovasc Diabetol, 24 Apr 2023 ↗)
Authors' conclusion
Antihyperglycemic therapies reduce MACE in an HbA1c-dependent manner. These findings indicate that HbA1c can be a useful marker of MACE risk reduction across a wide range of antihyperglycemic therapies, including drugs with pleiotropic effects. In contrast, HF is reduced not in an HbA1c-dependent but in a bodyweight-dependent manner. Notably, SGLT2i have shown class-specific benefits for HF beyond HbA1c or bodyweight reductions.
Study context
- Population
- Patients with T2D or prediabetes in randomized cardiovascular outcome trials (CVOTs) of antihyperglycemic therapies reporting both major adverse cardiovascular events (MACE) and heart failure (HF) outcomes (PubMed and EMBASE to 25 January 2023)
- Participants
- 256,524 patients35 trials
- Comparison
- Antihyperglycemic therapies vs control
- Outcome
- Relationships of HbA1c or bodyweight changes with MACE and HF outcomes
Methodological detailsrandom-effects meta-analyses
- Random-effects meta-analyses
Pooled result
As reported in the abstract
MACE and HF; meta-regression on HbA1c and bodyweight reductions
- Every 1% greater HbA1c reduction: reduction in RR of MACE
- 14% (95% CI 4-24; P = 0.010)
- Every 1 kg bodyweight reduction, but not HbA1c reduction: reduction in RR of HF
- 7% (95% CI 4-10; P < 0.001)
- Significant residual heterogeneity for HF
- P < 0.001
Further pooled results
MACE, overall
| RR (95% CI) | P value | ||
|---|---|---|---|
| Antihyperglycemic therapiesI2 = 36.5% | 0.91 (0.88–0.94) | P < 0.001 | |
| 0.512Relative risk (log scale) |
HF, overall
| RR (95% CI) | P value | ||
|---|---|---|---|
| Antihyperglycemic therapiesI2 = 75.9% | 0.95 (0.87–1.04) | P = 0.28 | |
| 0.512Relative risk (log scale) |
HF, subgroup SGLT2i
| RR (95% CI) | P value | ||
|---|---|---|---|
| SGLT2iI2 = 0.0% | 0.68 (0.62–0.75) | P < 0.001 | |
| 0.512Relative risk (log scale) |
Original publication
Efficacy of antihyperglycemic therapies on cardiovascular and heart failure outcomes: an updated meta-analysis and meta-regression analysis of 35 randomized cardiovascular outcome trials. Cardiovasc Diabetol. Published 19 March 2023. doi:10.
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