Table 2.

Bivariate and multivariate meta-regression models with the hazard ratio for major adverse cardiovascular events (MACE) as dependent variable.

	HR	95% CI		p
		Lower bound	Upper bound
Bivariate analyses
Achieved HbA1c at study end in the active arm (HbA1c ≤ 7.0% vs HbA1c > 7.0%) vs MACE
All trials‡ (143 study arms; n = 270,874; 20,724 events)	0.9579	0.8117	1.1097	0.256
SGLT2i, DPP4i, Pioglitazone or GLP1-RA in the active arm (73 study arms*; n = 197,498; 17,073 events)	0.9062	0.7985	0.9673	0.017
Change in HbA1c in the active arm compared to control (each reduction of 1%) vs MACE
All trials∅ (143 study arms; n=270,874; 20,724 events)	0.8979	0.7249	1.0171	0.109
SGLT2i, DPP4i, Pioglitazone or GLP1-RA in the active arm◇ (73 study arms*; n = 197,498; 17,073 events)	0.8477	0.7395	0.9246	<0.001
Multivariate analyses**
Achieved HbA1c at study end in the active arm (HbA1c ≤ 7.0% vs. HbA1c > 7.0%) vs. MACE
All trials‡‡ (121 study arms§; n = 243,713; 18,029 events)	0.8785	0.6471	1.0820	0.162
SGLT2i, DPP4i, Pioglitazone or GLP1-RA in the active arm (60 study arms*§; n = 191,032; 16,126 events)	0.8252	0.7111	0.9512	0.009
Change in HbA1c in the active arm compared to control (each reduction of 1%) vs. MACE
All trialsøø (119 study arms§; n = 240,227; 17,648 events)	0.8837	0.7019	0.9991	0.049
SGLT2i, DPP4i, Pioglitazone or GLP1-RA in the active arm◇◇ (60 study arms*§; n = 191,032; 16,126 events)	0.9046	0.7513	0.9798	0.011

^*Excluding RCTs with outlier HRs for MACE, defined as HR ≥ 2.0 or HR ≤ 0.5.

^**Adjusted for Time since the diagnosis of T2DM, follow-up time and type of ADT in the active arm. Adjusting variables were selected for their association with HR for MACE in bivariate analyses.

^§Some RCTs had missing data for covariates.

^‡I²: 5.31%, QE = 83.17 (p = 0.95); tau2: 0.010 (SE = 0.022).

I²: 12.12%, QE = 53.32 (p = 0.93); tau2: 0.010 (SE = 0.022).

^øI²: 2.76%, QE = 92.10 (p = 0.98); tau2: 0.010 (SE = 0.022).

^◇I²: 6.1%, QE = 67.55 (p = 0.98); tau2: 0.008 (SE = 0.023).

^‡‡I²: 0%, QE = 73.21 (p = 0.95); tau2: 0.014 (SE = 0.012).

I²: 0%, QE = 7.29 (p = 0.20); tau2: 0.010 (SE = 0.021).

^øøI²: 0%, QE = 85.56 (p = 0.98); tau2: 0.018 (SE = 0.027).

^◇◇I²: 0%, QE = 77.32 (p = 0.96); tau2: 0.008 (SE = 0.028).