Timing and Risk Factors for Hyperglycemia Associated With Anamorelin Administration

Background/Aim: 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.

Patients and Methods: 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.

Results: 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.

Conclusion: 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.