Predictive factors and the management of hyperglycemia in patients with acromegaly and Cushing’s disease receiving pasireotide treatment: post hoc analyses from the SOM230B2219 study
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Predictive factors and the management of hyperglycemia in patients with acromegaly and Cushing’s disease receiving pasireotide treatment : post hoc analyses from the SOM230B2219 study. / Feldt-Rasmussen, Ulla; Bolanowski, Marek; Zhang, Shao Ling; Yu, Yerong; Witek, Przemysław; Kalra, Pramila; Kietsiriroje, Noppadol; Piacentini, Andrea; Pedroncelli, Alberto M.; Samson, Susan L.
In: Frontiers in Endocrinology, Vol. 15, 1250822, 2024.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Predictive factors and the management of hyperglycemia in patients with acromegaly and Cushing’s disease receiving pasireotide treatment
T2 - post hoc analyses from the SOM230B2219 study
AU - Feldt-Rasmussen, Ulla
AU - Bolanowski, Marek
AU - Zhang, Shao Ling
AU - Yu, Yerong
AU - Witek, Przemysław
AU - Kalra, Pramila
AU - Kietsiriroje, Noppadol
AU - Piacentini, Andrea
AU - Pedroncelli, Alberto M.
AU - Samson, Susan L.
N1 - Publisher Copyright: Copyright © 2024 Feldt-Rasmussen, Bolanowski, Zhang, Yu, Witek, Kalra, Kietsiriroje, Piacentini, Pedroncelli and Samson.
PY - 2024
Y1 - 2024
N2 - Introduction: Pasireotide, a somatostatin receptor ligand, is approved for treating acromegaly and Cushing’s disease (CD). Hyperglycemia during treatment can occur because of the drug’s mechanism of action, although treatment discontinuation is rarely required. The prospective, randomized, Phase IV SOM230B2219 (NCT02060383) trial was designed to assess optimal management of pasireotide-associated hyperglycemia. Here, we investigated predictive factors for requiring antihyperglycemic medication during pasireotide treatment. Methods: Participants with acromegaly or CD initiated long-acting pasireotide 40 mg/28 days intramuscularly (acromegaly) or pasireotide 600 μg subcutaneously twice daily during pre-randomization (≤16 weeks). Those who did not need antihyperglycemic medication, were managed with metformin, or received insulin from baseline entered an observational arm ending at 16 weeks. Those who required additional/alternative antihyperglycemic medication to metformin were randomized to incretin-based therapy or insulin for an additional 16 weeks. Logistic-regression analyses evaluated quantitative and qualitative factors for requiring antihyperglycemic medication during pre-randomization. Results: Of 190 participants with acromegaly and 59 with CD, 88 and 15, respectively, did not need antihyperglycemic medication; most were aged <40 years (acromegaly 62.5%, CD 86.7%), with baseline glycated hemoglobin (HbA1c) <6.5% (<48 mmol/mol; acromegaly 98.9%, CD 100%) and fasting plasma glucose (FPG) <100 mg/dL (<5.6 mmol/L; acromegaly 76.1%, CD 100%). By logistic regression, increasing baseline HbA1c (odds ratio [OR] 3.6; P=0.0162) and FPG (OR 1.0; P=0.0472) and history of diabetes/pre-diabetes (OR 3.0; P=0.0221) predicted receipt of antihyperglycemic medication in acromegaly participants; increasing baseline HbA1c (OR 12.6; P=0.0276) was also predictive in CD participants. Investigator-reported hyperglycemia-related adverse events were recorded in 47.9% and 54.2% of acromegaly and CD participants, respectively, mainly those with diabetes/pre-diabetes. Conclusion: Increasing age, HbA1c, and FPG and pre-diabetes/diabetes were associated with increased likelihood of requiring antihyperglycemic medication during pasireotide treatment. These risk factors may be used to identify those who need more vigilant monitoring to optimize outcomes during pasireotide treatment.
AB - Introduction: Pasireotide, a somatostatin receptor ligand, is approved for treating acromegaly and Cushing’s disease (CD). Hyperglycemia during treatment can occur because of the drug’s mechanism of action, although treatment discontinuation is rarely required. The prospective, randomized, Phase IV SOM230B2219 (NCT02060383) trial was designed to assess optimal management of pasireotide-associated hyperglycemia. Here, we investigated predictive factors for requiring antihyperglycemic medication during pasireotide treatment. Methods: Participants with acromegaly or CD initiated long-acting pasireotide 40 mg/28 days intramuscularly (acromegaly) or pasireotide 600 μg subcutaneously twice daily during pre-randomization (≤16 weeks). Those who did not need antihyperglycemic medication, were managed with metformin, or received insulin from baseline entered an observational arm ending at 16 weeks. Those who required additional/alternative antihyperglycemic medication to metformin were randomized to incretin-based therapy or insulin for an additional 16 weeks. Logistic-regression analyses evaluated quantitative and qualitative factors for requiring antihyperglycemic medication during pre-randomization. Results: Of 190 participants with acromegaly and 59 with CD, 88 and 15, respectively, did not need antihyperglycemic medication; most were aged <40 years (acromegaly 62.5%, CD 86.7%), with baseline glycated hemoglobin (HbA1c) <6.5% (<48 mmol/mol; acromegaly 98.9%, CD 100%) and fasting plasma glucose (FPG) <100 mg/dL (<5.6 mmol/L; acromegaly 76.1%, CD 100%). By logistic regression, increasing baseline HbA1c (odds ratio [OR] 3.6; P=0.0162) and FPG (OR 1.0; P=0.0472) and history of diabetes/pre-diabetes (OR 3.0; P=0.0221) predicted receipt of antihyperglycemic medication in acromegaly participants; increasing baseline HbA1c (OR 12.6; P=0.0276) was also predictive in CD participants. Investigator-reported hyperglycemia-related adverse events were recorded in 47.9% and 54.2% of acromegaly and CD participants, respectively, mainly those with diabetes/pre-diabetes. Conclusion: Increasing age, HbA1c, and FPG and pre-diabetes/diabetes were associated with increased likelihood of requiring antihyperglycemic medication during pasireotide treatment. These risk factors may be used to identify those who need more vigilant monitoring to optimize outcomes during pasireotide treatment.
KW - acromegaly
KW - Cushing’s disease
KW - diabetes mellitus
KW - glucose intolerance
KW - hyperglycemia
KW - pasireotide
KW - pituitary adenoma
U2 - 10.3389/fendo.2024.1250822
DO - 10.3389/fendo.2024.1250822
M3 - Journal article
C2 - 38577574
AN - SCOPUS:85189428097
VL - 15
JO - Frontiers in Endocrinology
JF - Frontiers in Endocrinology
SN - 1664-2392
M1 - 1250822
ER -
ID: 401615831