No reactive hypoglycaemia in Type 2 diabetic patients after subcutaneous administration of GLP‐1 and intravenous glucose

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Abstract
SUMMARY Aims It has previously been shown that intravenous and subcutaneous administration of glucagon‐like peptide (GLP)‐1 concomitant with intravenous glucose results in reactive hypoglycaemia in healthy subjects. Since GLP‐1 is also effective in Type 2 diabetic patients and is presently being evaluated as a therapeutic agent in this disease, it is important to investigate whether GLP‐1 can cause hypoglycaemia in such patients. Methods Eight Type 2 diabetic patients (age 54 (49–67) years; body mass index 31 (27–38) kg/m2; HbA1c 9.4 (7.0–12.5)%) and seven matched non‐diabetic subjects (HbA1c 5.5 (5.2–5.8)%, fasting plasma glucose 5.4 (5.0–5.7) mmol/l) were given a subcutaneous injection of 1.5 nmol GLP‐1/kg body weight (maximally tolerated dose), and 15 min later, plasma glucose (PG) was raised to 15 mmol/l with an intravenous glucose bolus. Results Hypoglycaemia with a PG at or below 2.5 mmol/l was seen in five of the seven healthy subjects after 60–70 min, but PG spontaneously increased again, reaching 3.7 (3.3–4.0) mmol/l at 90 min. In the patients, PG fell slowly and stabilized at 8.6 (4.2–12.1) mmol/l after 80 min. In both groups, glucagon levels initially decreased, but later increased, exceeding basal levels in healthy subjects, in spite of persistent, high concentrations of GLP‐1 (P < 0.02). Conclusions Subcutaneous GLP‐1 plus intravenous glucose induced reactive hypoglycaemia in healthy subjects, but not in Type 2 diabetic patients. Therefore, a GLP‐1‐based therapy would not be expected to be associated with an increased risk of hypoglycaemia in Type 2 diabetes mellitus.

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