Effects on the glucagon response to hypoglycaemia during DPP-4 inhibition in elderly subjects with type 2 diabetes : A randomized, placebo-controlled study
(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.
(Less)
- author
- Farngren, Johan LU ; Persson, Margaretha LU and Ahrén, Bo LU
- organization
- publishing date
- 2018-08
- 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
-
- scopus:85046294840
- pmid:29645341
- 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
- 2024-06-24 14:30:39
@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}}, }