Stabilizing effect of exenatide in a patient with C-peptide-negative diabetes mellitus

Exenatide is an incretin mimetic licensed for treatment of Type 2 diabetes poorly controlled despite maximally tolerated doses of oral therapy. Similar in structure to the natural incretin hormone glucagon-like peptide 1 (GLP-1), it helps restore underlying pathophysiological abnormalities.

We report the successful use of exenatide, combined with insulin, in a 66-year-old woman initially diagnosed with Type 2 diabetes in 1989 but now exhibiting a Type 1 phenotype. Diet, lifestyle advice and oral glucose-lowering agents were commenced but persisting poor control necessitated insulin therapy in 2005. She later presented twice in diabetic ketoacidosis, suggesting conversion to a Type 1 phenotype (postprandial C-peptide < 94 pmol/l). Despite differing insulin regimens, control remained poor with frequent hyperglycaemic and hypoglycaemic excursions, severely impairing quality of life. Whilst an inpatient in 2007 [glycated haemoglobin (HbA(1c)) 10.2%, body mass index (BMI) 31.5 kg/m(2)] exenatide was commenced in an attempt to stabilize glycaemic control. Dramatic improvements were seen and continued. Eight months later, HbA(1c) had fallen by 2% with an 8-kg weight loss and 10-unit reduction in daily insulin dose. Quality of life dramatically improved. C-peptide remains undetectable.

This patient with features of both Type 1 and Type 2 diabetes benefited greatly from exenatide with insulin therapy. The improvement seen in glycaemic control could not be attributable to enhanced insulin secretion but could be as a result of a combination of the other incretin effects (postprandial glucagon suppression, delayed gastric emptying and weight loss secondary to increased satiety) all improving insulin sensitivity, reducing insulin dose and smoothing control.