Aims The autoimmune-mediated destruction of pancreatic β-cells in Type 1 diabetes mellitus renders patients deficient in two glucoregulatory peptide hormones, insulin and amylin. With insulin replacement alone, most patients do not achieve glycaemic goals. We aimed to determine the long-term efficacy and safety of adjunctive therapy with pramlintide, a synthetic human amylin analogue, in patients with Type 1 diabetes.
Methods In a double-blind, placebo-controlled, parallel-group, multicentre study, 651 patients with Type 1 diabetes (age 41 ± 13 years, HbA1c 8.9 ± 1.0%, mean ± sd) were randomized to mealtime injections of placebo or varying doses of pramlintide, in addition to their insulin therapy, for 52 weeks.
Results Addition of pramlintide [60 µg three times daily (TID) or four times daily (QID)] to insulin led to significant reductions in HbA1c from baseline to Week 52 of 0.29% (P < 0.011) and 0.34% (P < 0.001), respectively, compared with a 0.04% reduction in placebo group. Three times the proportion of pramlintide- than placebo-treated patients achieved an HbA1c of < 7%. The greater reduction in HbA1c with pramlintide was achieved without an increase in concomitant insulin use and was accompanied by a significant reduction in body weight from baseline to Week 52 of 0.4 kg in the 60 µg TID (P < 0.027) or QID (P < 0.040) pramlintide treatment groups, compared with a 0.8-kg gain in body weight in the placebo group. The most common adverse event in pramlintide-treated patients was transient, mild-to-moderate nausea.
Conclusions These results show that mealtime amylin replacement with pramlintide, as an adjunct to insulin therapy, improves long-term glycaemic and weight control in patients with Type 1 diabetes.