Saxagliptin co-therapy in C-peptide negative Type 1 diabetes does not improve counter-regulatory responses to hypoglycaemia

P. S. George, R. J. McCrimmon (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
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Aims: To test the hypothesis that dipeptidyl peptidase-4 inhibition in C-peptide negative Type 1 diabetes would reduce glucose variability and exposure to hypoglycaemia and therefore may indirectly enhance counter-regulatory responses to subsequent hypoglycaemia.
Methods: We conducted a 12-week double-blind, randomized, placebo-controlled crossover study. The study was conducted in a tertiary hospital outpatient clinic, with additional studies performed in a clinical research centre. After obtaining informed consent, we recruited 14 subjects with moderately well controlled Type 1 diabetes (HbA1c 64 ` 2 mmol/mol) of long duration (20.5 ` 2.7 years). The subjects received 12 weeks’ therapy with oral saxagliptin (5 mg) or placebo. Glucose variability, assessed via continuous glucose monitoring, together with frequency of hypoglycaemia, hypoglycaemia awareness and symptomatic, cognitive and counter-regulatory hormone responses to experimental hypoglycaemia, were assessed. Additional outcome measures included HbA1c level, weight, total daily insulin dose and adverse events.
Results: Saxagliptin co-therapy did not reduce glucose variability (low blood glucose index, average daily risk range), hypoglycaemia frequency or awareness and did not improve counter-regulatory hormonal responses during experimental hypoglycaemia (area under the curve for adrenaline 25 775 vs. 24 454, for placebo vs saxagliptin, respectively; P = 0.76).
Conclusions: No additional benefit of dipeptidyl peptidase-4 inhibition co-therapy with saxagliptin in the management of Type 1 diabetes was observed.
Original languageEnglish
Pages (from-to)1283-1290
Number of pages8
JournalDiabetic Medicine
Issue number9
Early online date7 Dec 2015
Publication statusPublished - 1 Sept 2016


  • Hypoglycaemia
  • Type 1 diabetes
  • Glucagon
  • Adrenaline

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)
  • Endocrinology


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