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Fig. 4 | Cardiovascular Diabetology

Fig. 4

From: Semaglutide reduces cardiovascular events regardless of metformin use: a post hoc subgroup analysis of SUSTAIN 6 and PIONEER 6

Fig. 4

Meta-analysis of effect on MACE by baseline metformin: A metformin; B no-metformin; C metformin vs no-metformin. Figures A and B compare a GLP-1RA with placebo. Figure C compares the effect of metformin or no-metformin in GLP-1RA trials. Analyses for SUSTAIN 6 and PIONEER 6 are based on a Cox proportional hazards model with treatment (semaglutide, placebo) by metformin subgroup as fixed factors, stratified by trial and CV risk group (established CVD and/or CKD vs risk factors), and adjusted by baseline variables: sex (male vs female), smoker (current, previous, never), previous MI/stroke/TIA (yes vs no), region (European Union, North America, other), antidiabetic treatment (yes vs no), diabetes duration, eGFR-MDRD and age. Trial duration (median follow-up in years) was: 2.1 (SUSTAIN 6); 1.3 (PIONEER 6); 1.6 (HARMONY OUTCOMES); 3.8 (LEADER); 5.4 (REWIND); 3.2 (EXSCEL); and 1.8 (AMPLITUDE-O). A includes patients receiving metformin; B includes patients not receiving metformin; and C includes the ratio between the hazard ratios for the two different groups, metformin and no-metformin. The fixed-effect model assumes all trials are estimating a common treatment effect; the random-effect model assumes the observed estimates of treatment effect can vary across trials. CI confidence interval, CKD chronic kidney disease, CV cardiovascular, CVD cardiovascular disease, eGFR estimated glomerular filtration rate. GLP-1RA glucagon-like peptide-1 receptor agonist, HR hazard ratio (GLP-1RA vs placebo), I2 inconsistency across estimates, MACE major adverse cardiovascular event, MDRD Modification of Diet in Renal Disease, MI myocardial infarction, RHR ratio between the hazard ratios in metformin vs no-metformin groups, TIA transient ischemic attack

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