Impact of DPP-4 inhibitors on plasma levels of BNP and NT-pro-BNP in type 2 diabetes mellitus

Liying Mu; Zhuo Wang; Jinmei Ren; Xiaowei Xiong; Zening Jin; Xin Liu

doi:10.1186/s13098-022-00797-x

February 14, 2022Diabetology & Metabolic SyndromeOpen Access

Impact of DPP-4 inhibitors on plasma levels of BNP and NT-pro-BNP in type 2 diabetes mellitus

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Why the study?

To determine the modulatory effect of dipeptidyl peptidase-4 inhibitors on brain natriuretic peptide and N-terminal pro-brain natriuretic peptide in patients with type 2 diabetes mellitus.

Does DPP-4i therapy reduce or modulate plasma levels of BNP and NT-pro-BNP in patients with type 2 diabetes mellitus?

Structured PICO

Does DPP-4i therapy reduce or modulate plasma levels of BNP and NT-pro-BNP in patients with type 2 diabetes mellitus?

P

Population

6,056 patients with type 2 diabetes mellitus pooled from 9 RCTs.

I

Intervention

Dipeptidyl peptidase-4 inhibitors (DPP-4i) as a class (including sitagliptin, alogliptin, vildagliptin, and linagliptin) administered as monotherapy or in addition to metformin or another antidiabetic agent for 0.5 to 48 months.

C

Comparator

Placebo or active control therapy (traditional antidiabetic agents including metformin, liraglutide, glargine, voglibose, glimepiride, and dapagliflozin).

O

Outcome

Net change in the BNP or NT-pro-BNP concentrations from baseline to the end of follow-up.surrogate

DPP-4 inhibitors have a neutral effect on plasma BNP and NT-pro-BNP levels in patients with type 2 diabetes, suggesting they do not directly modulate these key heart failure biomarkers.

Limitations

Differences in baseline BNP or NT-pro-BNP values and cardiovascular therapies across included studies
Few trials included in the pooled analysis, which could cause publication bias
Only investigated the impact on BNP/NT-pro-BNP and not other biomarkers of heart failure
Lack of long-term DPP-4i treatment trials to assess long-run impact

Implication

DPP-4i leave BNP/NT-proBNP unchanged in T2DM; confirms neutral biomarker effect and supports continued use without HF-related caution.

Abstract

BACKGROUND: Dipeptidyl peptidase-4 inhibitors (DPP-4i) decrease glucose levels by regulating incretin peptides in type 2 diabetes mellitus (T2DM). This study aimed to determine the modulatory effect of DPP-4i on brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in patients with T2DM. METHODS: PubMed, Embase and the Cochrane Library were systematically searched to identify randomized controlled trials (RCTs) evaluating the impact of DPP-4i on BNP or NT-pro-BNP. A fixed- or random-effects model was used for quantitative analysis, according to the heterogeneity. Sensitivity analysis and publication bias were performed using standard methods. RESULTS: Nine trials with 3056 patients with T2DM were included. Meta-analysis revealed that DPP-4i did not significantly modulate the BNP (0.21 pg/mL, 95% CI - 2.36-2.79) or NT-pro-BNP level (- 7.34 pg/mL, 95% CI - 24.27-9.59). DPP-4i demonstrated no stronger effect on modulating BNP (5.17 pg/mL, 95% CI - 7.48-17.82) or NT-pro-BNP (- 9.95 pg/mL, 95% CI - 44.61-24.71) than active comparators. Pooled analysis was robust and stable after sensitivity analysis. CONCLUSIONS: DPP-4i exhibits no significant effect on modulating BNP or NT-pro-BNP and shows no stronger effect than traditional antidiabetic agents in T2DM.