Abstract
Aims:
To investigate the effects of glucose-lowering agents on all-cause mortality, and cardiovascular and renal outcomes in adults with type 2 diabetes.
Methods:
A MEDLINE and EMBASE search was performed to identify RCTs, published up to February 28th ,2022, with a follow-up≥52 weeks, in which glucose-lowering drugs were compared with either placebo or active comparators. We included only trials reporting formal external adjudication of events. All-cause mortality, 3-point MACE (Major Cardiovascular Events), and hospitalization for heart failure (HHF) were considered as principal outcomes. Doubling of serum creatinine, worsening albuminuria, and renal death were considered as secondary endpoints.
Results:
We included RCT performed on metformin(n=17), pioglitazone (n=20), alpha-glucosidase inhibitors(n=9), insulin secretagogues(n=42), dipeptidyl-peptidase-4 inhibitors (DPP-4i;n=67), glucagon-like peptide-1 receptor agonists (GLP-1RA;n=45) or sodium glucose-transporter-2 inhibitors (SGLT-2i;n=42), and insulin(n=18). GLP-1RA and SGLT-2i was associated with a significant reduction in all-cause mortality (MH-OR, 95%CI: 0.88[0.83;0.95] and 0.85[0.79;0.91], respectively) and MACE (MH-OR, 95%CI: 0.89[0.84;0.94] and 0.90[0.84;0.96], respectively). SGLT-2i was associated with a reduced risk of HHF (MH-OR 0.68 [0.62;0.75]), worsening albuminuria (MH-OR 0.67[0.55;0.80]), and doubling of serum creatinine (MH-OR 0.58[0.44;0.79]). Metformin and pioglitazone were associated with a significantly lower risk of MACE (MH-OR 0.60[0.47;0.80] and 0.85[0.74;0.97], respectively), and pioglitazone with a higher risk of HHF (MH-OR 1.30[1.04;1.62]). Insulin secretagogues were associated with increased risk of all-cause mortality (MH-OR 1.12[1.01;1.24]) and MACE (MH-OR 1.19[1.02;1.39]).
Conclusions:
The results of this updated meta-analysis need to be considered in the choice of drug treatment for T2DM, which cannot be merely based on the effect of glucose-lowering drugs on long-term glycemic control. This article is protected by copyright. All rights reserved.
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