Abstract
Aims: In long-term clinical trials in patients with type 1 diabetes spanning a wide range
of HbA1c, addition of pramlintide to existing insulin regimens led to reductions in
HbA1c that were accompanied by weight loss and no increase in overall severe hypoglycemia
event rates. Given that weight gain and increased hypoglycemia risk contribute to
the difficulty of attaining HbA1c targets (< 7 %), the question arose whether pramlintide
could benefit patients approaching, but not reaching glycemic targets with insulin
alone. To address this question, we conducted a pooled analysis from 3 long-term clinical
trials, including all patients with an entry HbA1c between 7.0 % and 8.5 %. Methods: Within the subset of patients with an entry HbA1c between 7.0 % and 8.5 % (approximately
28 % of all patients enrolled in the 3 studies), 196 were treated with placebo + insulin
(baseline HbA1c 7.9 ± 0.4 %, body weight 76.0 ± 14.3 kg [mean ± SD]) and 281 with
pramlintide + insulin (baseline HbA1c 7.9 ± 0.4 %, body weight 75.4 ± 13.1 kg). Endpoints
included placebo-corrected changes from baseline to week 26 in HbA1c, body weight,
and the event rate of severe hypoglycemia. Results: Adjunctive therapy with pramlintide resulted in significant reductions in HbA1c and
body weight from baseline to week 26 (0.3 % and 1.8 kg, placebo-corrected treatment
differences, respectively, both p ≤ 0.0009). These changes occurred without an increase
in the overall risk of severe hypoglycemia (1.40 pramlintide vs. 1.86 placebo, events/patient-year
of exposure). Conclusions: Addition of pramlintide to insulin therapy may help patients with type 1 diabetes
who are approaching, but not yet reaching, glycemic targets with insulin alone to
achieve further reductions in HbA1c without concomitant weight gain and increased
risk of severe hypoglycemia.
Key words
HbA1c - pramlintide - type 1 diabetes - glycemic targets
References
christian.weyer@amylin.com
