Addition of pramlintide to insulin therapy lowers HbA1c in conjuction with weight loss in patients with type 2 diabetes approaching glycaemic targets

Abstract

Aim: Two long-term, randomized, double-blind, placebo-controlled clinical trials in insulin-using patients with type 2 diabetes, spanning a wide range of baseline glycaemic control, have shown that the addition of pramlintide, an analogue of the β-cell hormone amylin, to pre-existing insulin regimens results in reductions in HbA1c that are accompanied by weight loss. Methods: To assess whether this profile of pramlintide is observed in patients approaching, but not yet reaching, glycaemic targets, we conducted a pooled post hoc analysis of the two trials, including all patients with an entry HbA1c between 7.0 and 8.5%. Within this subset of patients, 80 were treated with placebo + insulin [baseline HbA1c 8.0 ± 0.3%, weight 87.3 ± 19.3 kg (mean ± s.d.)] and 86 with pramlintide (120 μg bid) + insulin [HbA1c 8.0 ± 0.4%, weight 92.5 ± 20.4 kg (mean ± s.d.)]. Endpoints included changes from baseline to Week 26 in HbA1c, body weight, and the event rate of severe hypoglycaemia. Results: Adjunctive therapy with pramlintide resulted in significant reductions in both HbA1c and body weight from baseline to Week 26 (-0.43% and -2.0 kg differences from placebo, respectively, both p < 0.001). These changes were achieved without a concomitant increase in the overall rate of severe hypoglycaemic events (0.13 pramlintide vs. 0.19 placebo, events/patient year of exposure). Conclusions: The data from this post hoc analysis indicate that the addition of pramlintide to insulin therapy may help patients with type 2 diabetes who are approaching, but not yet reaching, glycaemic targets to achieve further reductions in HbA1c without concomitant weight gain and increased risk of severe hypoglycaemia.