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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

  • Johan Farngren
  • Margaretha Persson
  • Bo Ahrén
Publishing year: 2018-08
Language: English
Pages: 1911-1920
Publication/Series: Diabetes, Obesity and Metabolism
Volume: 20
Issue: 8
Document type: Journal article
Publisher: Wiley-Blackwell

Abstract english

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.


  • Endocrinology and Diabetes
  • DPP-4 inhibition
  • Glucagon
  • Hypoglycaemia
  • Type 2 diabetes


  • Internal Medicine - Epidemiology
  • ISSN: 1462-8902
E-mail: johan [dot] farngren [at] med [dot] lu [dot] se

Research project participant



Research student

Medicine, Lund


Lund University Diabetes Centre, CRC, SUS Malmö, Jan Waldenströms gata 35, House 91:12. SE-214 28 Malmö. Telephone: +46 40 39 10 00