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

• Published in: Diabetic medicine Vol. 33; no. 9; pp. 1283 - 1290
• Main Authors: George, P. S., McCrimmon, R. J.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.09.2016; Wiley Subscription Services, Inc
• Subjects: Adamantane - analogs & derivatives; Adamantane - therapeutic use; Adult; Blood Glucose Self-Monitoring; Cross-Over Studies; Diabetes; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - metabolism; Dipeptides - therapeutic use; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Double-Blind Method; Drug Therapy, Combination; Epinephrine - metabolism; Female; Glucagon - metabolism; Glucose Clamp Technique; Humans; Hypoglycemia - chemically induced; Hypoglycemia - metabolism; Hypoglycemic Agents - therapeutic use; Insulin - metabolism; Insulin - therapeutic use; Male; Middle Aged; Monitoring, Ambulatory; Norepinephrine - metabolism
• ISSN: 0742-3071; 1464-5491; 1464-5491
• DOI: 10.1111/dme.13046

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. What's new? This study tested the novel hypothesis that dipeptidyl peptidase‐4 inhibitor co‐therapy in Type 1 diabetes would act indirectly to improve symptom and hormonal responses to hypoglycaemia. The hypothesis was rejected and no significant impact of dipeptidyl peptidase‐4 inhibitor therapy was seen on measures of glucose variability, hypoglycaemia counter‐regulation or glycaemic control. These findings do not support the use of dipeptidyl peptidase‐4 inhibitors in the management of C‐peptide‐negative Type 1 diabetes.