No Hypoglycemia After Subcutaneous Administration of Glucagon-Like Peptide-1 in Lean Type 2 Diabetic Patients and in Patients With Diabetes Secondary to Chronic Pancreatitis

Abstract

OBJECTIVE—Glucagon-like peptide 1 (GLP-1) is a proglucagon derivative secreted primarily from the L-cells of the small intestinal mucosa in response to the ingestion of meals. GLP-1 stimulates insulin secretion and inhibits glucagon secretion. It has previously been shown that intravenous or subcutaneous administration of GLP-1 concomitant with intravenous glucose results in hypoglycemia in healthy subjects. Because GLP-1 is also effective in type 2 diabetic patients and is currently being evaluated as a therapeutic agent, it is important to investigate whether GLP-1 may cause hypoglycemia in such patients. We have previously shown that GLP-1 does not cause hypoglycemia in obese type 2 diabetic patients with insulin resistance amounting to 5.4 ± 1.1 according to homeostasis model assessment (HOMA). In this study, we investigated diabetic patients with normal or close to normal insulin sensitivity. RESEARCH DESIGN AND METHODS—Eight lean type 2 diabetic patients (group 1) aged 60 years (range 50–72) with BMI 23.1 kg/m2 (20.3–25.5) and HbA1c 8.0% (6.9–11.4) and eight patients with type 2 diabetes secondary to chronic pancreatitis (group 2) aged 52 years (41–62) with BMI 21.9 kg/m2 (17.6–27.3) and HbA1c 7.8% (6.2–12.4) were given a subcutaneous injection of 1.5 nmol GLP-1/kg body wt. Then, 15 min later, at the time of peak GLP-1 concentration, plasma glucose (PG) was raised to 15 mmol/l with an intravenous glucose bolus. HOMA (mean ± SEM) showed insulin resistance amounting to 1.9 ± 0.3 and 1.7 ± 0.5 in the two groups, respectively. RESULTS—In both groups, PG decreased rapidly and stabilized at 7.5 mmol/l (range 3.9–10.1) and 7.2 mmol/l (3.1–10.9) in groups 1 and 2, respectively, after 90 min. Neither symptoms of hypoglycemia nor biochemical hypoglycemia were observed in any patient. CONCLUSIONS—We conclude that a GLP-1-based therapy would not be expected to be associated with an increased risk of hypoglycemia in insulin-sensitive type 2 diabetic patients.