Real-world experience with pasireotide-LAR in resistant acromegaly: a single center 1-year observation

Abstract

Context Pasireotide-LAR, a second-generation somatostatin receptor ligand (SRL), is recommended for patients with acromegaly as second-line treatment. Its efficacy and safety were assessed in clinical trials; however, the real-world evidence is still scarce. Objective The aim of this study was to evaluate the impact of 1-year treatment with pasireotide-LAR on disease control and glucose metabolism in acromegaly patients resistant to first-generation SRLs. Design A single-center prospective study. Methods Twenty-eight patients with active acromegaly or acrogigantism on first-generation SRLs following ineffective pituitary surgery were switched to treatment with pasireotide-LAR 40 or 60 mg i.m. every 28 days. To assess the efficacy of the treatment GH and IGF-1 levels were measured every 3 months. Safety of treatment was carefully evaluated, especially its impact on glucose metabolism. Results Complete biochemical control (GH ≤ 1 ng/mL and IGF-1 ≤ 1 × ULN) was achieved in 26.9% of patients and partial + complete response (GH ≤ 2.5 ng/mL and IGF-1 ≤ 1.3 × ULN) in 50.0% of patients. Mean GH level decrease was the largest within first 6 months (P = 0.0001) and mean IGF-1 level decreased rapidly within the first 3 months (P < 0.0001) and they remained reduced during the study. Blood glucose and HbA1c levels increased significantly within 3 months (P = 0.0001) and stayed on stable level thereafter. Otherwise, the treatment was well tolerated and clinical improvement was noticed in majority of patients. Conclusions This real-life study confirmed good effectiveness of pasireotide-LAR in patients resistant to first-generation SRLs. Pasireotide-LAR was overall safe and well tolerated, however significant glucose metabolism worsening was noted.

Pasireotide-Induced Shrinkage in GH and ACTH Secreting Pituitary Adenoma: A Systematic Review and Meta-Analysis

“…Data from the PAOLA study provided separate percentages of significant tumor shrinkage for PAS at 40 mg or 60 mg once monthly; considering that respectively 12 and 7 patients showed a reduction >25%, a significant shrinkage was reported in 19 out of 79 considered cases (24%) (4). Stelmachowska-Banaś et al described one patient with McCune-Albright's syndrome presenting with pituitary hyperplasia, without a visible adenoma at MRI; as its pituitary volume decreased during treatment, the patient was included in the group with significant tumor shrinkage (27). No study provided information about macro-to microadenoma ratio.…”

Secondary diabetes mellitus in acromegaly

“…Notably, the majority of patients in the above trials are diabetic or prediabetic at baseline [ 116 – 118 ] and the main effect of PASI is to convert prediabetes to DM [ 116 , 117 ]. Glycemic deterioration presents early, approximately at 3 months, but remains stable thereafter [ 117 , 119 ]. Based on real-world data, the mean increases in FBG and HbA1c are 13.06 mg/dl and 0.42% respectively, with 23.1 % of patients having deranged glycemic control [ 119 ].…”

“…Glycemic deterioration presents early, approximately at 3 months, but remains stable thereafter [ 117 , 119 ]. Based on real-world data, the mean increases in FBG and HbA1c are 13.06 mg/dl and 0.42% respectively, with 23.1 % of patients having deranged glycemic control [ 119 ]. Similarly to first-generation SRLS, PASI-related hyperglycemia is reversible upon drug discontinuation [ 120 ].…”

“…These observations suggest that diabetogenic effects of PASI might involve other somatostatin receptors activated by PASI but not by AP102, such as SSR1 and somatostatin receptor subtype 3 (SSR3); of note, both are abundantly expressed in beta cells [ 105 , 122 ]. Finally, glucose outcomes on treatment with PASI are correlated with age, HbA1c/glycemic status at baseline, and history of hypertension or dyslipidemia [ 118 , 119 ].…”

“…The presence of cardiovascular disease, heart failure and chronic kidney disease has not been considered in suggested management here, but, if present, the current guidelines for T2DM with glucagon-like peptide 1 receptor agonizts (GLP-1RA) or sodium-glucose co-transporter 2 inhibitors (SGLT2i) should be followed. * only in cases of controlled acromegaly, ↑ increase, ↑↑ big increase ↓ decrease, ↓↓ big decrease, → results into, + plus, ± plus or minus, DM diabetes mellitus, FFA free fatty acid, GH growth hormone, GIP glucose-dependent insulinotropic polypeptide, GLP-1 glucagon-like peptide 1, IMAT intrermuscular adipose tissue, IR insulin receptor, IRS-1 insulin receptor substrate 1, NAMPT nicotinamide phosphorybosultransferase (also known as visfatin), PI3K phosphatidylinositol-3-kinase, PKCθ protein kinase C theta, SAT subcutanenous adipose tissue, SGLT2is sodium-glucose co-transporter 2 inhibitors, SSR1 somatostatin receptor subtype 1, SSR3 somatostatin receptor subtype 3, SSR5 somatostatin receptor subtype 5, TAT total adipose tissue [ 5 , 28 , 33 – 36 , 38 , 39 , 41 – 43 , 45 – 48 , 50 , 51 , 60 – 63 , 65 , 66 , 68 , 69 , 72 , 84 , 94 , 114 – 119 , 121 , 139 – 141 , 144 , 148 ]…”