Author’s response to “Is pramlintide a safe and effective adjunct therapy for patients with type 1 diabetes?”

Response to: Edelman SV et al. (2007) Is pramlintide a safe and effective adjunct therapy for patients with type 1 diabetes? Nat Clin Pract Endocrinol Metab [10.1038/ncpendmet0506]

To read Monnier’s original commentary, click here

I have read with interest the response of Edelman et al. to my commentary.¹ On the basis of their own observations,² and of a recent paper published by Marrero et al.³, Edelman et al. conclude that the clinical benefits of pramlintide treatments (loss of body weight [−1.3 kg], improvement in postprandial glucose excursions, and reduction in insulin doses [−12%]) largely overcome the adverse events (gastrointestinal effects and increased rates of hypoglycemic episodes) that occurred in a minority of patients, especially in those who experienced more nausea. Considering the results of Marrero et al.³ who reported that the pramlintide-treated patients were globally satisfied by the adjunction of pramlintide to insulin, I can admit that the relatively low rate of adverse events does not impair the acceptability of the pramlintide treatment. However, I would remain much more skeptical about the long-term efficacy of pramlintide. In both the studies of Edelman et al.² and Marrero et al.,³ the patients exhibited mean HbA_1c levels slightly above 8.0% at baseline and mean reductions in HbA_1c levels of 0.4–0.5%, which were approximately similar in the pramlintide and the placebo-treated groups. These results seem to indicate that pramlintide treatments fail to achieve the recommended HbA_1c targets in most patients with HbA_1c levels above 8%. Furthermore, these observations raise the question whether pramlintide treatments can specifically prevent the risk for developing diabetic complications. If we hypothesize that such an effect exists, it could be due to the ability of pramlintide to reduce the postprandial glucose excursions and as a consequence the acute glucose fluctuations. According to these remarks, and from a general point of view, further long-term studies comparing the effects of pramlintide and placebo treatments should be conducted in insulin-treated patients with HbA_1c levels in the range of 7–8%. Such studies might answer the important question whether pramlintide is helpful as an adjunct to insulin in order to maintain glucose control as near to normal as safely possible⁴ and to reduce the risk for developing diabetic complications.