Abstract
PurposeTo explore the effects of pegvisomant (PEGV) on glucose metabolism in patients with acromegaly within ACROSTUDY, an international, observational, prospective safety surveillance study.MethodsPatients were retrospectively divided into two cohorts, with (DM group) or without diabetes mellitus (no-DM). Parameters of glucose metabolism and IGF-I values were analyzed yearly both cross-sectionally for 4 years (yrs) and longitudinally at 1 and 4–5 yrs of PEGV treatment.ResultsAmong 1762 patients, 510 (28.9%) had DM before PEGV start. At cross-sectional analyses, in the DM group mean blood glucose was 140.0 ± 58.7 mg/dl at baseline, 116.4 ± 44.8 mg/dl at year 1 and 120.0 ± 44.3 mg/dl at yr 4. Mean HbA1c was 6.6 ± 1.2 % at yr 1 vs. 7.0 ± 1.4 % at baseline. HbA1c was above 6.5% in 61.9% at baseline and ranged from 45.4 to 53.8% at subsequent yearly time points. At the 4-yr longitudinal analysis, in the DM group (n = 109), mean blood glucose decreased by 20.2 mg/dl at yr 4, mean HbA1c was 7.0 ± 1.5% at baseline vs. 6.8 ± 1.4%. Patients achieved IGF-I normalization in 52.1% and 57.4% of cases in the DM and no-DM groups, respectively at 1 year. The mean daily PEGV dose (mg/day) was higher in the DM group (18.2 vs. 15.3) while the absolute change of IGF-I values from baseline was similar in both groups. PEGV was well tolerated in both groups without any unexpected AEs.ConclusionsPatients with DM had a moderate decrease in mean fasting glucose values during PEGV treatment.
Highlights
Growth hormone (GH) has anabolic effects, and antagonizes insulin actions as it stimulates lipolysis, gluconeogenesis, and glycogenolysis [1, 2]
It was reported that classically used somatostatin analogues (SSAs) may have a marginal negative clinical impact on glucose homeostasis in acromegaly [8] while in a head-to-head study vs. octreotide, hyperglycemia-related adverse events (AEs) were more common with long-acting pasireotide, a SSA targeting a broader range of somatostatin receptor subtypes [9]
We investigated parameters of glucose metabolism in patients followed in ACROSTUDY, using the database freeze performed on December 4th, 2012
Summary
Growth hormone (GH) has anabolic effects, and antagonizes insulin actions as it stimulates lipolysis, gluconeogenesis, and glycogenolysis [1, 2]. Medical treatment modalities for acromegaly may in turn reduce insulin resistance and increase insulin sensitivity [7]. These treatments include somatostatin analogues (SSAs), dopamine agonists, and the GH-receptor (GHR) antagonist pegvisomant (PEGV) [3]. The mode of action of SSAs is complex as they have direct and indirect effects on glycemic control, regardless of GH and IGF-I [10, 11]. Compared to SSA treatment, PEGV appears to be superior in improving glycemic control during the treatment of acromegaly patients [15, 16], and it has been shown to improve peripheral and hepatic insulin sensitivity in acromegaly [17, 18]
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