No increased risk of hypoglycaemic episodes during 48 h of subcutaneous glucagon-like-peptide-1 administration in fasting healthy subjects

Susanne Lerche; Liselotte Soendergaard; Joergen Rungby; Niels Moeller; Jens Juul Holst; Ole E Schmitz; Birgitte Brock

doi:10.1111/j.1365-2265.2008.03510.x

No increased risk of hypoglycaemic episodes during 48 h of subcutaneous glucagon-like-peptide-1 administration in fasting healthy subjects

Susanne Lerche, Liselotte Soendergaard, Joergen Rungby, Niels Moeller, Jens Juul Holst, Ole E Schmitz, Birgitte Brock

Endocrinology and Metabolism

19 Citations (Scopus)

Abstract

OBJECTIVE: It is uncertain whether the ability to avoid hypoglycaemia during fasting is preserved, and the risk of reactive hypoglycaemia after an oral glucose stimulus following a prolonged fasting period is increased at augmented glucagon-like peptide-1 (GLP-1) levels. DESIGN: A randomized, double-blind placebo-controlled cross-over study in eight healthy men to assess the safety, in terms of hypoglycaemia, of a continuously infused pharmacological dose of native GLP-1 during long-term fasting. After an overnight fast the fasting period continued for 48 h and was followed by a 3-h oral glucose tolerance test (OGTT). GLP-1(7-36 amide) or placebo was continuously infused subcutaneously and titrated to a dose of 4.8 pmol/kg per min. RESULTS: Two subjects in the GLP-1 group and one subject in the placebo group were withdrawn due to protocol specified plasma glucose (PG) < or = 2.8 mm and neuroglycopaenic symptoms. The infusion of GLP-1 resulted in pharmacological levels of intact GLP-1. During the fasting period PG, insulin and C-peptide levels declined and glucagon, GH and free fatty acid (FFA) levels increased with no differences between GLP-1 and placebo. During OGTT circulating levels of insulin and C-peptide were higher with GLP-1 infusion. However, PG was similar during GLP-1 vs. placebo infusions. GLP-1 infusion increased norepinephrine and cortisol levels during OGTT. CONCLUSION: The counter-regulatory response during 48 h of subcutaneous GLP-1 infusion was preserved despite long-term fasting with no apparent increased risk of hypoglycaemic episodes. No reactive hypoglycaemia was observed when the fast was followed by an OGTT. Thus use of long-acting GLP-1 analogues may not increase the risk of hypoglycaemia.

Original language	English
Journal	Clinical Endocrinology
Volume	71
Issue number	4
Pages (from-to)	500-6
Number of pages	6
ISSN	0300-0664
DOIs	https://doi.org/10.1111/j.1365-2265.2008.03510.x
Publication status	Published - 2008

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10.1111/j.1365-2265.2008.03510.x

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@article{86355390335611df8ed1000ea68e967b,

title = "No increased risk of hypoglycaemic episodes during 48 h of subcutaneous glucagon-like-peptide-1 administration in fasting healthy subjects",

abstract = "OBJECTIVE: It is uncertain whether the ability to avoid hypoglycaemia during fasting is preserved, and the risk of reactive hypoglycaemia after an oral glucose stimulus following a prolonged fasting period is increased at augmented glucagon-like peptide-1 (GLP-1) levels. DESIGN: A randomized, double-blind placebo-controlled cross-over study in eight healthy men to assess the safety, in terms of hypoglycaemia, of a continuously infused pharmacological dose of native GLP-1 during long-term fasting. After an overnight fast the fasting period continued for 48 h and was followed by a 3-h oral glucose tolerance test (OGTT). GLP-1(7-36 amide) or placebo was continuously infused subcutaneously and titrated to a dose of 4.8 pmol/kg per min. RESULTS: Two subjects in the GLP-1 group and one subject in the placebo group were withdrawn due to protocol specified plasma glucose (PG) < or = 2.8 mm and neuroglycopaenic symptoms. The infusion of GLP-1 resulted in pharmacological levels of intact GLP-1. During the fasting period PG, insulin and C-peptide levels declined and glucagon, GH and free fatty acid (FFA) levels increased with no differences between GLP-1 and placebo. During OGTT circulating levels of insulin and C-peptide were higher with GLP-1 infusion. However, PG was similar during GLP-1 vs. placebo infusions. GLP-1 infusion increased norepinephrine and cortisol levels during OGTT. CONCLUSION: The counter-regulatory response during 48 h of subcutaneous GLP-1 infusion was preserved despite long-term fasting with no apparent increased risk of hypoglycaemic episodes. No reactive hypoglycaemia was observed when the fast was followed by an OGTT. Thus use of long-acting GLP-1 analogues may not increase the risk of hypoglycaemia.",

author = "Susanne Lerche and Liselotte Soendergaard and Joergen Rungby and Niels Moeller and Holst, {Jens Juul} and Schmitz, {Ole E} and Birgitte Brock",

note = "Keywords: Adult; Blood Glucose; C-Peptide; Cross-Over Studies; Fasting; Fatty Acids, Nonesterified; Glucagon-Like Peptide 1; Glucose Tolerance Test; Human Growth Hormone; Humans; Hypoglycemia; Infusions, Subcutaneous; Insulin; Male; Norepinephrine; Peptide Fragments",

year = "2008",

doi = "10.1111/j.1365-2265.2008.03510.x",

language = "English",

volume = "71",

pages = "500--6",

journal = "Clinical Endocrinology",

issn = "0300-0664",

publisher = "Wiley-Blackwell",

number = "4",

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TY - JOUR

T1 - No increased risk of hypoglycaemic episodes during 48 h of subcutaneous glucagon-like-peptide-1 administration in fasting healthy subjects

AU - Lerche, Susanne

AU - Soendergaard, Liselotte

AU - Rungby, Joergen

AU - Moeller, Niels

AU - Holst, Jens Juul

AU - Schmitz, Ole E

AU - Brock, Birgitte

N1 - Keywords: Adult; Blood Glucose; C-Peptide; Cross-Over Studies; Fasting; Fatty Acids, Nonesterified; Glucagon-Like Peptide 1; Glucose Tolerance Test; Human Growth Hormone; Humans; Hypoglycemia; Infusions, Subcutaneous; Insulin; Male; Norepinephrine; Peptide Fragments

PY - 2008

Y1 - 2008

N2 - OBJECTIVE: It is uncertain whether the ability to avoid hypoglycaemia during fasting is preserved, and the risk of reactive hypoglycaemia after an oral glucose stimulus following a prolonged fasting period is increased at augmented glucagon-like peptide-1 (GLP-1) levels. DESIGN: A randomized, double-blind placebo-controlled cross-over study in eight healthy men to assess the safety, in terms of hypoglycaemia, of a continuously infused pharmacological dose of native GLP-1 during long-term fasting. After an overnight fast the fasting period continued for 48 h and was followed by a 3-h oral glucose tolerance test (OGTT). GLP-1(7-36 amide) or placebo was continuously infused subcutaneously and titrated to a dose of 4.8 pmol/kg per min. RESULTS: Two subjects in the GLP-1 group and one subject in the placebo group were withdrawn due to protocol specified plasma glucose (PG) < or = 2.8 mm and neuroglycopaenic symptoms. The infusion of GLP-1 resulted in pharmacological levels of intact GLP-1. During the fasting period PG, insulin and C-peptide levels declined and glucagon, GH and free fatty acid (FFA) levels increased with no differences between GLP-1 and placebo. During OGTT circulating levels of insulin and C-peptide were higher with GLP-1 infusion. However, PG was similar during GLP-1 vs. placebo infusions. GLP-1 infusion increased norepinephrine and cortisol levels during OGTT. CONCLUSION: The counter-regulatory response during 48 h of subcutaneous GLP-1 infusion was preserved despite long-term fasting with no apparent increased risk of hypoglycaemic episodes. No reactive hypoglycaemia was observed when the fast was followed by an OGTT. Thus use of long-acting GLP-1 analogues may not increase the risk of hypoglycaemia.

AB - OBJECTIVE: It is uncertain whether the ability to avoid hypoglycaemia during fasting is preserved, and the risk of reactive hypoglycaemia after an oral glucose stimulus following a prolonged fasting period is increased at augmented glucagon-like peptide-1 (GLP-1) levels. DESIGN: A randomized, double-blind placebo-controlled cross-over study in eight healthy men to assess the safety, in terms of hypoglycaemia, of a continuously infused pharmacological dose of native GLP-1 during long-term fasting. After an overnight fast the fasting period continued for 48 h and was followed by a 3-h oral glucose tolerance test (OGTT). GLP-1(7-36 amide) or placebo was continuously infused subcutaneously and titrated to a dose of 4.8 pmol/kg per min. RESULTS: Two subjects in the GLP-1 group and one subject in the placebo group were withdrawn due to protocol specified plasma glucose (PG) < or = 2.8 mm and neuroglycopaenic symptoms. The infusion of GLP-1 resulted in pharmacological levels of intact GLP-1. During the fasting period PG, insulin and C-peptide levels declined and glucagon, GH and free fatty acid (FFA) levels increased with no differences between GLP-1 and placebo. During OGTT circulating levels of insulin and C-peptide were higher with GLP-1 infusion. However, PG was similar during GLP-1 vs. placebo infusions. GLP-1 infusion increased norepinephrine and cortisol levels during OGTT. CONCLUSION: The counter-regulatory response during 48 h of subcutaneous GLP-1 infusion was preserved despite long-term fasting with no apparent increased risk of hypoglycaemic episodes. No reactive hypoglycaemia was observed when the fast was followed by an OGTT. Thus use of long-acting GLP-1 analogues may not increase the risk of hypoglycaemia.

U2 - 10.1111/j.1365-2265.2008.03510.x

DO - 10.1111/j.1365-2265.2008.03510.x

M3 - Journal article

C2 - 19094067

SN - 0300-0664

VL - 71

SP - 500

EP - 506

JO - Clinical Endocrinology

JF - Clinical Endocrinology

IS - 4

ER -

No increased risk of hypoglycaemic episodes during 48 h of subcutaneous glucagon-like-peptide-1 administration in fasting healthy subjects

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