Timing and Risk Factors for Hyperglycemia Associated With Anamorelin Administration

Anamorelin, a ghrelin receptor agonist, alleviates cancer cachexia by stimulating appetite and growth hormone secretion but may induce hyperglycemia via insulin resistance. Although clinical trials have reported a low incidence of this adverse effect, severe cases have been described, and evidence regarding onset timing and risk factors in real-world practice is scarce.

This single-center retrospective study included patients with non-small-cell lung, gastric, pancreatic, and colorectal cancers who received anamorelin between June 2021 and September 2023. Hyperglycemia was defined as a blood glucose level of >200 mg/dl. The primary endpoints were incidence, time to onset, and risk factors. Clinical data were extracted from electronic medical records, and logistic regression analyses were performed.

Among the 129 patients included in the study, pancreatic cancer was the most common malignancy (38.0%). Hyperglycemia occurred in 29.5% of patients, with Grade ≥3 events occurring in 20.2% of cases. Among affected patients, 81.6% developed hyperglycemia within 28 days of treatment initiation. Multivariate analysis identified diabetes mellitus [odds ratio (OR)=7.081; 95% confidence interval (CI)=2.774-18.076; p<0.001] and alanine aminotransferase (ALT) level >42 IU/l (OR=4.746; 95%CI=1.417-15.895; p=0.012) as independent predictors. The concomitant use of corticosteroids and neurokinin-1 receptor antagonists was not significantly associated with the incidence of hyperglycemia.

Anamorelin-induced hyperglycemia occurred in nearly one-third of patients, predominantly within the first month of therapy. Diabetes mellitus and elevated ALT level were independent predictors, highlighting the need for close glucose monitoring in at-risk patients.