Association between somatostatin analogues and diabetes mellitus in gastroenteropancreatic neuroendocrine tumor patients: A Surveillance, Epidemiology, and End Results‐Medicare analysis of 5235 patients

Abstract

Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are increasingly common malignancies and tend to have favorable long-term prognoses.Somatostatin analogues (SSA) are a first-line treatment for many NETs. Short-term experiments suggest an association between SSAs and hyperglycemia. However, it is unknown whether there is a relationship between SSAs and clinically significant hyperglycemia causing development of diabetes mellitus (DM), a chronic condition with significant morbidity and mortality.Aim: In this study, we aimed to compare risk of developing DM in patients treated with SSA vs no SSA treatment.Methods and Results: Using the Surveillance, Epidemiology, and End Results (SEER) database and linked Medicare claims , we identified patients age 65+ with no prior DM diagnosis and a GEP-NET in the stomach, small intestine, appendix, colon, rectum, or pancreas. We used χ 2 tests to compare SSA-treated and SSAuntreated patients and multivariable Cox regression to assess risk factors for developing DM. Among 8464 GEP-NET patients, 5235 patients had no prior DM and were included for analysis. Of these, 784 (15%) patients received SSAs. In multivariable analysis, the hazard ratio of developing DM with SSA treatment was 1.19, which was not statistically significant (95% CI 0.95-1.49). Significant risk factors for DM included black race, Hispanic ethnicity, prior pancreatic surgery, prior chemotherapy, tumor size >2 cm, pancreas tumors, and higher Charlson scores. Conclusion:DM was very common in GEP-NET patients, affecting 53% of our cohort. Despite prior studies suggesting an association between SSAs and hyperglycemia, our analysis found similar risk of DM in SSA-treated and SSA-untreated GEP-NET patients. Further studies are needed to better understand this relationship. As NET patients have increasingly prolonged survival, it is crucial to identify chronic conditions such as DM that these patients may be at elevated risk for.

Visceral Obesity Is Associated with Shorter Progression-Free Survival in Well-Differentiated Gastro-Entero-Pancreatic Neuroendocrine Neoplasia

“…Notwithstanding, our results show that elevated waist circumference was associated with shorter PFS, regardless of the fact that BMI, MetS, hypertension, dyslipidemia, and hyperglycemia were not found to be associated with poorer WD-GEP-NEN prognosis [ 43 ]. A 2021 analysis on the Surveillance, Epidemiology, and End Results (SEER) databases and linked Medicare claims (1991–2016), compared the risk for T2D in somatostatin analogues (SSA) treated vs. no-SSA treated patients, did not find significant differences, which suggests that GEP-NEN patients have a higher risk for T2D, independently of the hyperglycemic effects of treatment [ 44 ]. Similar findings were published by our group [ 17 ].…”

Genome analysis identifies differences in the transcriptional targets of duodenal versus pancreatic neuroendocrine tumours

“…Progress in genetic testing, advances in imaging and increased awareness are the major reasons for the increased incidence in gastroenteropancreatic neuroendocrine tumours (GEP-NETs). [1][2][3] Although GEP-NETs comprise ~0.5% of all gastrointestinal (GI) cancers and are the second most prevalent…”

Prescription patterns of somatostatin analogs in patients with acromegaly and neuroendocrine tumors

“…This finding implies that the medical team should be aware of these possible comorbidities and actively search for them to provide timely treatment that can impact cardiovascular outcomes; additionally, acromegaly itself is associated with arterial hypertension, diabetes mellitus and cardiomyopathies [ 20 , 29 ]. Furthermore, it should be noted that treatment with somatostatin analogs, especially pasireotide LAR, has been associated with hyperglycemia [ 30 , 31 ]. Similarly, among the patients with neuroendocrine tumors, it was determined that main comorbidities were arterial hypertension and diabetes mellitus, as has been reported in epidemiological studies that identified these diagnoses and obesity as the main comorbidities of neuroendocrine tumors [ 10 , 15 ].…”