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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
Author(s) -
Farngren Johan,
Persson Margaretha,
Ahrén Bo
Publication year - 2018
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13316
Subject(s) - sitagliptin , glucagon , medicine , metformin , endocrinology , placebo , crossover study , type 2 diabetes , hypoglycemia , diabetes mellitus , sitagliptin phosphate , randomized controlled trial , insulin , alternative medicine , pathology
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, 74 years [range 65‐86]; mean HbA1c, 51.5 mmol/mol [6.9%]) received sitagliptin (100 mg once daily) as add‐on therapy or placebo for 4 weeks 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 3.0 mmol/L), followed by lunch. Results Glucagon levels after breakfast and lunch, and the glucagon response at 3.5 mmol/L, were lower after sitagliptin than after placebo. However, the glucagon response to hypoglycaemia at 3.1 mmol/L did not differ significantly between the two. Similarly, the noradrenaline, adrenaline and cortisol responses were lower with sitagliptin than with placebo at 3.5 mmol/L, but not at 3.1 mmol/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 3.5 mmol/L glucose, but maintain the glucagon response to hypoglycaemia at 3.1 mmol/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.