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Effects on the glucagon response to hypoglycaemia during DPP-4 inhibition in elderly subjects with type 2 diabetes : A randomized, placebo-controlled study

Farngren, Johan LU ; Persson, Margaretha LU orcid and Ahrén, Bo LU (2018) In Diabetes, Obesity and Metabolism 20(8). p.1911-1920
Abstract

Aims: Maintainance of glucagon response to hypoglycaemia is important as a safeguard against hypoglycaemia during glucose-lowering therapy in type 2 diabetes. During recent years, DPP-4 (dipeptidyl peptidase-4) inhibition has become more commonly used in elderly patients. However, whether DPP-4 inhibition affects the glucagon response to hypoglycaemia in the elderly is not known and was the aim of this study. Methods: In a single-centre, double-blind, randomized, placebo-controlled crossover study, 28 subjects with metformin-treated type 2 diabetes (17 male, 11 female; mean age, 74years [range 65-86]; mean HbA1c, 51.5mmol/mol [6.9%]) received sitagliptin (100mg once daily) as add-on therapy or placebo for 4weeks with a 4-week washout... (More)

Aims: Maintainance of glucagon response to hypoglycaemia is important as a safeguard against hypoglycaemia during glucose-lowering therapy in type 2 diabetes. During recent years, DPP-4 (dipeptidyl peptidase-4) inhibition has become more commonly used in elderly patients. However, whether DPP-4 inhibition affects the glucagon response to hypoglycaemia in the elderly is not known and was the aim of this study. Methods: In a single-centre, double-blind, randomized, placebo-controlled crossover study, 28 subjects with metformin-treated type 2 diabetes (17 male, 11 female; mean age, 74years [range 65-86]; mean HbA1c, 51.5mmol/mol [6.9%]) received sitagliptin (100mg once daily) as add-on therapy or placebo for 4weeks with a 4-week washout period in between. After each treatment period, the subjects underwent a standard breakfast test, followed by a 2-step hyperinsulinaemic hypoglycaemic clamp (target 3.5 and 3.0mmol/L), followed by lunch. Results: Glucagon levels after breakfast and lunch, and the glucagon response at 3.5mmol/L, were lower after sitagliptin than after placebo. However, the glucagon response to hypoglycaemia at 3.1mmol/L did not differ significantly between the two. Similarly, the noradrenaline, adrenaline and cortisol responses were lower with sitagliptin than with placebo at 3.5mmol/L, but not at 3.1mmol/L glucose. Responses in pancreatic polypeptide did not differ between the two. Conclusions: Elderly subjects with metformin-treated type 2 diabetes have lower glucagon levels at 3.5mmol/L glucose, but maintain the glucagon response to hypoglycaemia at 3.1mmol/L during DPP-4 inhibition, which safeguards against hypoglycaemia and may contribute to decreasing the risk of hypoglycaemia by DPP-4 inhibition in this age group.

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author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
DPP-4 inhibition, Glucagon, Hypoglycaemia, Type 2 diabetes
in
Diabetes, Obesity and Metabolism
volume
20
issue
8
pages
1911 - 1920
publisher
Wiley-Blackwell
external identifiers
  • pmid:29645341
  • scopus:85046294840
ISSN
1462-8902
DOI
10.1111/dom.13316
language
English
LU publication?
yes
id
0fb2adc2-6b4c-4467-bac4-e22351bf4f51
date added to LUP
2018-05-17 14:56:30
date last changed
2024-03-18 09:40:33
@article{0fb2adc2-6b4c-4467-bac4-e22351bf4f51,
  abstract     = {{<p>Aims: Maintainance of glucagon response to hypoglycaemia is important as a safeguard against hypoglycaemia during glucose-lowering therapy in type 2 diabetes. During recent years, DPP-4 (dipeptidyl peptidase-4) inhibition has become more commonly used in elderly patients. However, whether DPP-4 inhibition affects the glucagon response to hypoglycaemia in the elderly is not known and was the aim of this study. Methods: In a single-centre, double-blind, randomized, placebo-controlled crossover study, 28 subjects with metformin-treated type 2 diabetes (17 male, 11 female; mean age, 74years [range 65-86]; mean HbA1c, 51.5mmol/mol [6.9%]) received sitagliptin (100mg once daily) as add-on therapy or placebo for 4weeks with a 4-week washout period in between. After each treatment period, the subjects underwent a standard breakfast test, followed by a 2-step hyperinsulinaemic hypoglycaemic clamp (target 3.5 and 3.0mmol/L), followed by lunch. Results: Glucagon levels after breakfast and lunch, and the glucagon response at 3.5mmol/L, were lower after sitagliptin than after placebo. However, the glucagon response to hypoglycaemia at 3.1mmol/L did not differ significantly between the two. Similarly, the noradrenaline, adrenaline and cortisol responses were lower with sitagliptin than with placebo at 3.5mmol/L, but not at 3.1mmol/L glucose. Responses in pancreatic polypeptide did not differ between the two. Conclusions: Elderly subjects with metformin-treated type 2 diabetes have lower glucagon levels at 3.5mmol/L glucose, but maintain the glucagon response to hypoglycaemia at 3.1mmol/L during DPP-4 inhibition, which safeguards against hypoglycaemia and may contribute to decreasing the risk of hypoglycaemia by DPP-4 inhibition in this age group.</p>}},
  author       = {{Farngren, Johan and Persson, Margaretha and Ahrén, Bo}},
  issn         = {{1462-8902}},
  keywords     = {{DPP-4 inhibition; Glucagon; Hypoglycaemia; Type 2 diabetes}},
  language     = {{eng}},
  number       = {{8}},
  pages        = {{1911--1920}},
  publisher    = {{Wiley-Blackwell}},
  series       = {{Diabetes, Obesity and Metabolism}},
  title        = {{Effects on the glucagon response to hypoglycaemia during DPP-4 inhibition in elderly subjects with type 2 diabetes : A randomized, placebo-controlled study}},
  url          = {{http://dx.doi.org/10.1111/dom.13316}},
  doi          = {{10.1111/dom.13316}},
  volume       = {{20}},
  year         = {{2018}},
}