Elsevier

Metabolism

Volume 52, Issue 12, December 2003, Pages 1638-1642
Metabolism

Effect of pramlintide on A1C and body weight in insulin-treated African Americans and Hispanics with type 2 diabetes: a pooled post hoc analysis

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Abstract

An unresolved problem in the management of type 2 diabetes is that improvement of glycemic control with insulin, insulin secretagogues, and insulin sensitizers is often accompanied by undesired weight gain. This problem is of particular concern in ethnic groups with a high propensity for diabetes and obesity, such as African Americans and Hispanics. Two 1-year, randomized, double-blind, placebo-controlled clinical trials in insulin-treated patients with type 2 diabetes have shown that adjunctive therapy with pramlintide, an analog of the human β-cell hormone amylin, reduces A1C with concomitant weight loss, rather than weight gain. To assess the effect of pramlintide in various ethnic groups with type 2 diabetes using insulin, we conducted a pooled post hoc analysis of the 2 trials, which included all Caucasian (n = 315), African American (n = 47), and Hispanic (n = 48) patients (age 57 years, A1C 9.1%, body mass index [BMI] 33 kg/m2, mean values) who completed 52 weeks of treatment with either pramlintide (120 μg twice daily or 150 μg 3 times a day) or placebo. Primary endpoints included changes from baseline to week 52 in A1C and body weight. Collectively, pramlintide-treated patients achieved significant reductions from baseline in both A1C and body weight (placebo-corrected treatment effects at week 52: −0.5% and −2.6 kg, respectively, both P < .0001). The simultaneous reduction in A1C and body weight at week 52 was evident across all 3 ethnic groups and appeared to be most pronounced in African Americans (−0.7%, −4.1 kg), followed by Caucasians (−0.5%, −2.4 kg) and Hispanics (−0.3%, −2.3 kg). The glycemic improvement with pramlintide was not associated with an increased incidence of hypoglycemia over the entire study period (43% pramlintide v 40% placebo). Nausea, the most common adverse event associated with pramlintide treatment, was mostly mild and confined to the first 4 weeks of therapy (25% pramlintide v 16% placebo) with comparable patterns in the 3 ethnic groups. Thus, pending further experience, the combined improvement in glycemic and weight control with pramlintide treatment appears to be generalizable to a broad population of mixed ethnicity.

Section snippets

Study design

The designs of the 2 long-term, randomized, placebo-controlled, double-blind studies included in this pooled post hoc analysis have been described in detail previously.24, 25 In brief, both studies included patients with type 2 diabetes and utilized an add-on design, ie, pramlintide or placebo (injected subcutaneously twice daily or 3 times a day before the major meals) were added to pre-existing insulin regimens. Study medication (placebo or pramlintide), but not insulin or oral medications,

Patient disposition and baseline demographics

Of the 1,194 patients enrolled in the 2 studies, 410 (34%) were randomized to either placebo or pramlintide (120 μg twice daily and 150 μg 3 times a day) and had completed the study. Of those, 315 (77%) were Caucasian, 47 (11%) were African American, and 48 (12%) were Hispanic (Table 1).

Among the 3 ethnic groups, most of the key baseline demographics were well balanced. However, African Americans and Hispanics had a slightly higher mean baseline A1C than Caucasians, and African Americans also

Discussion

It is well established that there are substantial ethnic differences in the prevalence and pathophysiology of type 2 diabetes. However, little is known about potential ethnic differences in the response to different antihyperglycemic therapies. The aim of the present post hoc analysis was to assess the long-term effect of pramlintide, an amylin analog in late-stage clinical development, on both A1C and body weight in insulin-treated African Americans and Hispanics with type 2 diabetes, 2 ethnic

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