Background: Pramlintide, a human amylin analogue, is a potential new adjunctive therapy to insulin for patients with type 1 diabetes and insulin-using patients with type 2 diabetes. Early clinical trials have shown a transient increased risk of hypoglycaemia in some patients at the time of initiating pramlintide therapy. This may be the result of combining the postprandial glucose, lowering effect of pramlintide with the existing hypoglycaemic potential of insulin without appropriate adjustment of insulin doses. However, the possibility that pramlintide may exert an independent detrimental effect on the physiological responses to insulin-induced hypoglycaemia needs to be excluded.
Methods: We conducted three separate randomized, placebo-controlled studies in patients with type 1 diabetes treated with adjunctive pramlintide. These studies utilized pramlintide at high doses (either 0.1-1 mg pramlintide daily or 0.1-0.8 mg pramlintide four times a day for 5 or 6 days) as well as doses closer to those anticipated for therapeutic usage (30, 100 or 300 microg three times daily for 14 days), and examined the hormonal, metabolic and symptomatic responses to an insulin-infusion hypoglycaemic challenge conducted at baseline and after days of therapy.
Results and conclusion: Pramlintide had no effect on the counter-regulatory hormonal, metabolic and symptomatic responses to hypoglycaemia. These findings demonstrated that pramlintide, when used as adjunctive therapy to insulin in patients with type 1 diabetes, has no independent effect on the response to hypoglycaemia.