Postprandial renal haemodynamic effect of lixisenatide vs once-daily insulin-glulisine in patients with type 2 diabetes on insulin-glargine: An 8-week, randomised, open-label trial

Lennart Tonneijck; Marcel H A Muskiet; Mark M Smits; Trynke Hoekstra; Mark H H Kramer; A H Jan Danser; Michaela Diamant; Jaap A Joles; Daniël H van Raalte

doi:10.1111/dom.12985

Postprandial renal haemodynamic effect of lixisenatide vs once-daily insulin-glulisine in patients with type 2 diabetes on insulin-glargine: An 8-week, randomised, open-label trial

Lennart Tonneijck
, Marcel H A Muskiet
, Mark M Smits
, Trynke Hoekstra
, Mark H H Kramer
, A H Jan Danser
, Michaela Diamant
, Jaap A Joles
, Daniël H van Raalte

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

AIM: To determine whether lixisenatide, a prandial short-acting glucagon-like peptide receptor agonist (GLP-1RA), ameliorates postprandial glomerular hyperfiltration in patients with type 2 diabetes mellitus (T2DM) compared with insulin-glulisine (iGlu).

METHODS: Postprandial renal haemodynamic effects of 8-week treatment with lixisenatide 20 µg vs once-daily titrated iGlu were measured in 35 overweight patients with T2DM inadequately controlled on insulin-glargine, with or without metformin [mean ± SD age 62 ± 7 years, HbA1c 8.0% ± 0.9%, estimated glomerular filtration rate (GFR) 85 ± 12 mL/min/1.73 m2 , median (IQR) urinary albumin/creatinine ratio 1.5 (0.9-3.0) mg/mmol]. After a standardised breakfast, GFR (primary endpoint) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippuric acid renal clearance, respectively, based on timed urine sampling. Intrarenal haemodynamic functions were estimated using Gomez equations.

RESULTS: Compared with iGlu, lixisenatide did not affect GFR [+0.1 mL/min/1.73 m2 (95% CI -9 to 9)], ERPF [-17 mL/min/1.73 m2 (-61 to 26)], other (intra-)renal haemodynamics or renal damage markers, but increased fractional sodium excretion [+0.25% (0.09-0.41)] and urinary pH [+0.7 (0.3-1.2)]. Plasma renin, angiotensin-II and aldosterone were unchanged. Lixisenatide and iGlu reduced HbA1c similarly, by 0.8% ± 0.1% and 0.6% ± 0.1%, respectively, while postprandial glucose was lower with lixisenatide (P = .002). Compared with iGlu, lixisenatide reduced bodyweight [-1.4 kg (-2.5 to -0.2)] and increased postprandial mean arterial pressure [+9 mm Hg (4-14)].

CONCLUSION: Eight-week lixisenatide treatment does not affect postprandial (intra-)renal haemodynamics compared with iGlu when added to insulin-glargine in patients with T2DM without overt nephropathy. Prolonged lixisenatide treatment has a sustained natriuretic effect, which is in contrast to previous reports on long-acting GLP-1RA, reduces body weight and increases postprandial blood pressure compared with iGlu.

TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02276196.

Original language	English
Pages (from-to)	1669-1680
Number of pages	12
Journal	Diabetes, Obesity & Metabolism
Volume	19
Issue number	12
DOIs	https://doi.org/10.1111/dom.12985
Publication status	Published - Dec 2017

Keywords

GLP-1 receptor agonist
diabetes
glomerular filtration rate
glomerular hyperfiltration
glomerular pressure
glucagon-like peptide-1
insulin-glulisine
lixisenatide
natriuresis
renal function
renal haemodynamics
type 2 diabetes

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10.1111/dom.12985

Tonneijck_et_al-2017-Diabetes,_Obesity_and_Metabolism (1)Final published version, 1.62 MBLicence: Taverne

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Tonneijck, L., Muskiet, M. H. A., Smits, M. M., Hoekstra, T., Kramer, M. H. H., Danser, A. H. J., Diamant, M., Joles, J. A., & van Raalte, D. H. (2017). Postprandial renal haemodynamic effect of lixisenatide vs once-daily insulin-glulisine in patients with type 2 diabetes on insulin-glargine: An 8-week, randomised, open-label trial. Diabetes, Obesity & Metabolism, 19(12), 1669-1680. https://doi.org/10.1111/dom.12985

@article{16e5aa3153bc4212b43b163b31a1b308,

title = "Postprandial renal haemodynamic effect of lixisenatide vs once-daily insulin-glulisine in patients with type 2 diabetes on insulin-glargine: An 8-week, randomised, open-label trial",

abstract = "AIM: To determine whether lixisenatide, a prandial short-acting glucagon-like peptide receptor agonist (GLP-1RA), ameliorates postprandial glomerular hyperfiltration in patients with type 2 diabetes mellitus (T2DM) compared with insulin-glulisine (iGlu).METHODS: Postprandial renal haemodynamic effects of 8-week treatment with lixisenatide 20 µg vs once-daily titrated iGlu were measured in 35 overweight patients with T2DM inadequately controlled on insulin-glargine, with or without metformin [mean ± SD age 62 ± 7 years, HbA1c 8.0\% ± 0.9\%, estimated glomerular filtration rate (GFR) 85 ± 12 mL/min/1.73 m2 , median (IQR) urinary albumin/creatinine ratio 1.5 (0.9-3.0) mg/mmol]. After a standardised breakfast, GFR (primary endpoint) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippuric acid renal clearance, respectively, based on timed urine sampling. Intrarenal haemodynamic functions were estimated using Gomez equations.RESULTS: Compared with iGlu, lixisenatide did not affect GFR [+0.1 mL/min/1.73 m2 (95\% CI -9 to 9)], ERPF [-17 mL/min/1.73 m2 (-61 to 26)], other (intra-)renal haemodynamics or renal damage markers, but increased fractional sodium excretion [+0.25\% (0.09-0.41)] and urinary pH [+0.7 (0.3-1.2)]. Plasma renin, angiotensin-II and aldosterone were unchanged. Lixisenatide and iGlu reduced HbA1c similarly, by 0.8\% ± 0.1\% and 0.6\% ± 0.1\%, respectively, while postprandial glucose was lower with lixisenatide (P = .002). Compared with iGlu, lixisenatide reduced bodyweight [-1.4 kg (-2.5 to -0.2)] and increased postprandial mean arterial pressure [+9 mm Hg (4-14)].CONCLUSION: Eight-week lixisenatide treatment does not affect postprandial (intra-)renal haemodynamics compared with iGlu when added to insulin-glargine in patients with T2DM without overt nephropathy. Prolonged lixisenatide treatment has a sustained natriuretic effect, which is in contrast to previous reports on long-acting GLP-1RA, reduces body weight and increases postprandial blood pressure compared with iGlu.TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02276196.",

keywords = "GLP-1 receptor agonist, diabetes, glomerular filtration rate, glomerular hyperfiltration, glomerular pressure, glucagon-like peptide-1, insulin-glulisine, lixisenatide, natriuresis, renal function, renal haemodynamics, type 2 diabetes",

author = "Lennart Tonneijck and Muskiet, \{Marcel H A\} and Smits, \{Mark M\} and Trynke Hoekstra and Kramer, \{Mark H H\} and Danser, \{A H Jan\} and Michaela Diamant and Joles, \{Jaap A\} and \{van Raalte\}, \{Dani{\"e}l H\}",

note = "Publisher Copyright: {\textcopyright} 2017 John Wiley \& Sons Ltd",

year = "2017",

month = dec,

doi = "10.1111/dom.12985",

language = "English",

volume = "19",

pages = "1669--1680",

journal = "Diabetes, Obesity \& Metabolism",

issn = "1462-8902",

publisher = "John Wiley \& Sons Inc.",

number = "12",

}

Tonneijck, L, Muskiet, MHA, Smits, MM, Hoekstra, T, Kramer, MHH, Danser, AHJ, Diamant, M, Joles, JA & van Raalte, DH 2017, 'Postprandial renal haemodynamic effect of lixisenatide vs once-daily insulin-glulisine in patients with type 2 diabetes on insulin-glargine: An 8-week, randomised, open-label trial', Diabetes, Obesity & Metabolism, vol. 19, no. 12, pp. 1669-1680. https://doi.org/10.1111/dom.12985

Postprandial renal haemodynamic effect of lixisenatide vs once-daily insulin-glulisine in patients with type 2 diabetes on insulin-glargine: An 8-week, randomised, open-label trial. / Tonneijck, Lennart; Muskiet, Marcel H A; Smits, Mark M et al.
In: Diabetes, Obesity & Metabolism, Vol. 19, No. 12, 12.2017, p. 1669-1680.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Postprandial renal haemodynamic effect of lixisenatide vs once-daily insulin-glulisine in patients with type 2 diabetes on insulin-glargine

T2 - An 8-week, randomised, open-label trial

AU - Tonneijck, Lennart

AU - Muskiet, Marcel H A

AU - Smits, Mark M

AU - Hoekstra, Trynke

AU - Kramer, Mark H H

AU - Danser, A H Jan

AU - Diamant, Michaela

AU - Joles, Jaap A

AU - van Raalte, Daniël H

PY - 2017/12

Y1 - 2017/12

N2 - AIM: To determine whether lixisenatide, a prandial short-acting glucagon-like peptide receptor agonist (GLP-1RA), ameliorates postprandial glomerular hyperfiltration in patients with type 2 diabetes mellitus (T2DM) compared with insulin-glulisine (iGlu).METHODS: Postprandial renal haemodynamic effects of 8-week treatment with lixisenatide 20 µg vs once-daily titrated iGlu were measured in 35 overweight patients with T2DM inadequately controlled on insulin-glargine, with or without metformin [mean ± SD age 62 ± 7 years, HbA1c 8.0% ± 0.9%, estimated glomerular filtration rate (GFR) 85 ± 12 mL/min/1.73 m2 , median (IQR) urinary albumin/creatinine ratio 1.5 (0.9-3.0) mg/mmol]. After a standardised breakfast, GFR (primary endpoint) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippuric acid renal clearance, respectively, based on timed urine sampling. Intrarenal haemodynamic functions were estimated using Gomez equations.RESULTS: Compared with iGlu, lixisenatide did not affect GFR [+0.1 mL/min/1.73 m2 (95% CI -9 to 9)], ERPF [-17 mL/min/1.73 m2 (-61 to 26)], other (intra-)renal haemodynamics or renal damage markers, but increased fractional sodium excretion [+0.25% (0.09-0.41)] and urinary pH [+0.7 (0.3-1.2)]. Plasma renin, angiotensin-II and aldosterone were unchanged. Lixisenatide and iGlu reduced HbA1c similarly, by 0.8% ± 0.1% and 0.6% ± 0.1%, respectively, while postprandial glucose was lower with lixisenatide (P = .002). Compared with iGlu, lixisenatide reduced bodyweight [-1.4 kg (-2.5 to -0.2)] and increased postprandial mean arterial pressure [+9 mm Hg (4-14)].CONCLUSION: Eight-week lixisenatide treatment does not affect postprandial (intra-)renal haemodynamics compared with iGlu when added to insulin-glargine in patients with T2DM without overt nephropathy. Prolonged lixisenatide treatment has a sustained natriuretic effect, which is in contrast to previous reports on long-acting GLP-1RA, reduces body weight and increases postprandial blood pressure compared with iGlu.TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02276196.

AB - AIM: To determine whether lixisenatide, a prandial short-acting glucagon-like peptide receptor agonist (GLP-1RA), ameliorates postprandial glomerular hyperfiltration in patients with type 2 diabetes mellitus (T2DM) compared with insulin-glulisine (iGlu).METHODS: Postprandial renal haemodynamic effects of 8-week treatment with lixisenatide 20 µg vs once-daily titrated iGlu were measured in 35 overweight patients with T2DM inadequately controlled on insulin-glargine, with or without metformin [mean ± SD age 62 ± 7 years, HbA1c 8.0% ± 0.9%, estimated glomerular filtration rate (GFR) 85 ± 12 mL/min/1.73 m2 , median (IQR) urinary albumin/creatinine ratio 1.5 (0.9-3.0) mg/mmol]. After a standardised breakfast, GFR (primary endpoint) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippuric acid renal clearance, respectively, based on timed urine sampling. Intrarenal haemodynamic functions were estimated using Gomez equations.RESULTS: Compared with iGlu, lixisenatide did not affect GFR [+0.1 mL/min/1.73 m2 (95% CI -9 to 9)], ERPF [-17 mL/min/1.73 m2 (-61 to 26)], other (intra-)renal haemodynamics or renal damage markers, but increased fractional sodium excretion [+0.25% (0.09-0.41)] and urinary pH [+0.7 (0.3-1.2)]. Plasma renin, angiotensin-II and aldosterone were unchanged. Lixisenatide and iGlu reduced HbA1c similarly, by 0.8% ± 0.1% and 0.6% ± 0.1%, respectively, while postprandial glucose was lower with lixisenatide (P = .002). Compared with iGlu, lixisenatide reduced bodyweight [-1.4 kg (-2.5 to -0.2)] and increased postprandial mean arterial pressure [+9 mm Hg (4-14)].CONCLUSION: Eight-week lixisenatide treatment does not affect postprandial (intra-)renal haemodynamics compared with iGlu when added to insulin-glargine in patients with T2DM without overt nephropathy. Prolonged lixisenatide treatment has a sustained natriuretic effect, which is in contrast to previous reports on long-acting GLP-1RA, reduces body weight and increases postprandial blood pressure compared with iGlu.TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02276196.

KW - GLP-1 receptor agonist

KW - diabetes

KW - glomerular filtration rate

KW - glomerular hyperfiltration

KW - glomerular pressure

KW - glucagon-like peptide-1

KW - insulin-glulisine

KW - lixisenatide

KW - natriuresis

KW - renal function

KW - renal haemodynamics

KW - type 2 diabetes

UR - https://www.scopus.com/pages/publications/85026289827

U2 - 10.1111/dom.12985

DO - 10.1111/dom.12985

M3 - Article

C2 - 28449402

SN - 1462-8902

VL - 19

SP - 1669

EP - 1680

JO - Diabetes, Obesity & Metabolism

JF - Diabetes, Obesity & Metabolism

IS - 12

ER -

Postprandial renal haemodynamic effect of lixisenatide vs once-daily insulin-glulisine in patients with type 2 diabetes on insulin-glargine: An 8-week, randomised, open-label trial

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