Glucagon-like peptide-1: effect on pro-atrial natriuretic peptide in healthy males

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Healthy males (n=12). Intervention: Native GLP1(7-36) amide infusion vs. Placebo (0.9% saline containing 1% human albumin). Primary outcome: Plasma proANP concentration (p=0.32).

Q: What does this research mean for the field?

Native GLP-1 infusion stimulates urinary sodium excretion without altering plasma proANP or proBNP concentrations in healthy humans, indicating GLP-1-mediated natriuresis is not driven by an ANP-dependent pathway. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

Jeppe Skov; Jens J. Holst; Jens Peter Gøtze; Jørgen Frøkiær; Jens Sandahl Christiansen

doi:10.1530/ec-13-0087

December 10, 2013Endocrine ConnectionsOpen Access

Glucagon-like peptide-1: effect on pro-atrial natriuretic peptide in healthy males

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Key result

Native GLP1 infusion increased urinary sodium excretion by ~40% without changing plasma proANP concentrations in healthy young males.

Why the study?

Does a 2-hour native GLP1 infusion increase plasma proANP concentrations in healthy young males?

Key Points

To determine whether a glucagon-like peptide-1 (GLP1) and atrial natriuretic peptide (ANP) axis exists in humans by evaluating proANP concentrations during GLP1 infusion.
Randomized, double-blinded, placebo-controlled, single-day crossover study in 12 healthy young males receiving a 2-hour infusion of native GLP1 (1.25 pmol/kg per min) or placebo.
Plasma mid-region proANP and N-terminal proBNP concentrations were measured along with urinary sodium excretion and vital signs.
GLP1 infusion increased baseline GLP1 concentrations nearly tenfold (P < 0.001) and elevated urinary sodium excretion by ~40% (P < 0.001), which rapidly returned toward baseline when infusion stopped.
Plasma proANP concentrations were not affected by GLP1 infusion (P = 0.32), and no changes were observed in proBNP levels.
GLP1 infusion had no acute effect on systolic blood pressure (P = 0.31) or diastolic blood pressure (P = 0.63), but heart rate transiently increased by approximately six beats per minute (P = 0.01).

Study Design

Type

RCT (n=12)

Blinding

Double-blind

Randomization

Randomized cross-over

Multicenter

No

Structured PICO

Does a 2-hour native GLP1 infusion increase plasma proANP concentrations in healthy young males?

P

Population

12 healthy young males (mean age 23.4 years, 0% female) with normal physical and laboratory screenings, studied in a single-day cross-over trial.

I

Intervention

Synthetic human native GLP1(7-36) amide intravenous infusion at 1.25 pmol/kg per min dissolved in 0.9% saline containing 1% human albumin for 2 hours, on a background of continuous isotonic 0.9% saline infusion (750 ml/h)

C

Comparator

Placebo infusion (solvent alone: 0.9% saline containing 1% human albumin) for 2 hours, separated by a 2-hour washout period in a cross-over design, with both groups receiving continuous isotonic 0.9% saline infusion (750 ml/h)

O

Outcome

Plasma mid-regional pro-atrial natriuretic peptide (proANP) concentration measured every 20 minutes during the single-day study using an automated mid-region-directed proANP immunoassaysurrogate

Main Result

p-value: p=0.32

Limitations

Not originally designed to evaluate a GLP1-ANP axis; proANP analyses were performed post-hoc
Did not measure ANP directly because blood samples were not properly pretreated for the unstable peptide
High saline infusion rates and frequent blood sampling may have induced period effects
Study was not originally designed to evaluate a GLP1-ANP axis and proANP analyses were performed post-hoc
Did not measure ANP itself because blood samples were not properly pretreated for this highly unstable peptide

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Implication

Acute native GLP1 infusion induces marked natriuresis without altering plasma proANP or proBNP levels in healthy men, challenging the existence of a functional GLP1-ANP axis in humans.

Abstract

The antihypertensive actions of glucagon-like peptide-1 (GLP1) receptor agonists have been linked to the release of atrial natriuretic peptide (ANP) in mice. Whether a GLP1-ANP axis exists in humans is unknown. In this study, we examined 12 healthy young males in a randomized, controlled, double-blinded, single-day, cross-over study to evaluate the effects of a 2-h native GLP1 infusion. Plasma proANP concentrations were measured by an automated mid-region-directed proANP immunoassay and N-terminal pro B-type natriuretic peptide (BNP) on Roche Modular E170. Urine was collected for measurements of sodium excretion. Although GLP1 infusion increased the urinary sodium excretion markedly, there were no significant changes in either proANP or proBNP concentrations. When GLP1 infusion was stopped, sodium excretion declined rapidly. As proANP concentration reflects ANP secretion, our data could not confirm the existence of a GLP1-ANP axis in humans. Especially, the natriuretic effects of GLP1 seem unlikely to be mediated exclusively via ANP.

Discussion

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Cite This Study

Skov et al. (2013) conducted an RCT in Healthy males (n=12). Native GLP1(7-36) amide infusion vs. Placebo (0.9% saline containing 1% human albumin) was evaluated on Plasma proANP concentration (p=0.32). Native GLP1 infusion increased urinary sodium excretion by ~40% without changing plasma proANP concentrations in healthy young males.

synapsesocial.com/papers/6a79441c06bbdce36102036d https://doi.org/10.1530/ec-13-0087

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Glucagon-like peptide-1: effect on pro-atrial natriuretic peptide in healthy males

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Glucagon-like peptide-1: effect on pro-atrial natriuretic peptide in healthy males

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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