What is the clinical evidence from this study?

Study design: Meta-Analysis. Population: Type 2 diabetes (n=171253). Intervention: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) vs. Other anti-diabetic agents (Insulin, DPP4i, GLP1a, TZD, MET, SU) and placebo. Primary outcome: Incident heart failure or hospitalization for heart failure (OR 0.68, 95% CI 0.59-0.78).

What does this research mean for the field?

Sodium-glucose co-transporter 2 (SGLT2) inhibitors are associated with the lowest risk of heart failure among all classes of anti-diabetic medications, demonstrating significant superiority over DPP-4 inhibitors, GLP-1 agonists, insulin, and thiazolidinediones. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

April 8, 2019Open Access

Comparative outcomes of heart failure among existent classes of anti-diabetic agents: a network meta-analysis of 171,253 participants from 91 randomized controlled trials

DYDaya YangSun Yat-sen University XHXin HeUniversity of Chicago HLHuiwei LiangGuangzhou Psychiatric Hospital

Key Result

Sodium-glucose co-transporter 2 inhibitors were associated with the lowest risk of heart failure, significantly superior to DPP-4 inhibitors (OR 0.68), GLP-1 agonists (OR 0.65), insulin (OR 0.75), and thiazolidinediones (OR 0.46).

Study Design

Type

Meta-Analysis (n=171,253)

Structured PICO

Do different classes of anti-diabetic agents reduce incident heart failure or hospitalization for heart failure in individuals with type 2 diabetes?

Population

171,253 individuals with type 2 diabetes from 91 randomized controlled trials. Mean age ranged from 44.0 to 72.5 years, male proportion ranged from 41.3 to 77.6%. Included patients with coronary heart disease, high cardiovascular risk, and renal impairment.

Intervention

Anti-diabetic agents as a class (SGLT2 inhibitors, GLP-1 receptor agonists, DPP-4 inhibitors, metformin, sulfonylureas, thiazolidinediones, insulin) with treatment duration of more than 24 weeks

Comparator

Pairwise comparisons among all classes of anti-diabetic medications and placebo

Outcome

Incident heart failure or hospitalization for heart failurehard clinical

SGLT2 inhibitors are associated with the lowest risk of incident heart failure among all classes of anti-diabetic medications in patients with type 2 diabetes.

Main Result

Effect estimate: OR 0.68 (95% CI 0.59-0.78)

Limitations

Heterogeneity of trial designs and reporting styles of the included studies
Modest event rates in general
Inability to differentiate between heart failure with reduced or preserved ejection fraction
Lack of patient-level data to account for other variables correlated with heart failure

Abstract

BACKGROUND: The cardiovascular (CV) safety in terms of heart failure among different classes of treatment remains largely unknown. We sought to assess the comparative effect of these agents on heart failure outcomes. METHODS: This study was registered in the International Prospective Register of Systematic Reviews (CRD 42016042063). MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials were searched. For the primary outcomes reported previously, studies between Jan 1, 1980 and June 30, 2016 were screened, and subsequently updated till Jan 24, 2019. We performed network meta-analysis to obtain estimates for the outcomes of heart failure, in particular by rankograms for ranking of heart failure risk as well as by pairwise comparisons among all classes of anti-diabetic medications. RESULTS: A total of 91 trials were included, among which were 171,253 participants and 4163 reported cases of heart failure events. As for rankograms, the surface under the cumulative ranking curves (SUCRA) of sodium-glucose co-transporters 2 and thiazolidinediones were 93.4% and 4.3%, respectively, signifying the lowest and highest risk of heart failure, respectively. As for pairwise comparisons in the network, sodium-glucose co-transporters 2 were significantly superior to insulin (OR: 0.75, 95% CI 0.62-0.91), dipeptidyl peptidase 4 inhibitors (OR: 0.68, 95% CI 0.59-0.78), glucagon-like peptide-1 receptor agonists (OR: 0.65, 95% CI 0.54-0.78), and thiazolidinediones (OR: 0.46, 95% CI 0.27-0.77) in terms of heart failure risk. Furthermore, in an exploratory analysis among subjects with underlying heart failure or at risk of heart failure, the superiority of sodium-glucose co-transporters 2 was still significant. CONCLUSIONS: In terms of heart failure risk, sodium-glucose co-transporters 2 were the most favorable option among all classes of anti-diabetic medications.

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