Cancer Res Treat.  2016 Jan;48(1):171-179. 10.4143/crt.2014.292.

The Impact of Diabetes Mellitus and Metformin Treatment on Survival of Patients with Advanced Pancreatic Cancer Undergoing Chemotherapy

• Choi Y
• Kim TY
• Oh DY
• Lee KH
• Han SW
• Im SA
• Kim TY
• Bang YJ

• KMID: 2152273
• DOI: http://doi.org/10.4143/crt.2014.292

Abstract

PURPOSE
A causal relationship between diabetes mellitus (DM) and pancreatic cancer is well established. However, in patients with advanced pancreatic cancer (APC) who receive palliative chemotherapy, the impact of DM on the prognosis of APC is unclear.
MATERIALS AND METHODS
We retrospectively enrolled APC patients who received palliative chemotherapy between 2003 and 2010. The patients were stratified according to the status of DM, in accordance with 2010 DM criteria (American Heart Association/American Diabetes Association). DM at least 2 years' duration prior to diagnosis of APC was defined as remote-onset DM (vs. recent-onset).
RESULTS
Of the 349 APC patients, 183 (52.4%) had DM. Among the patients with DM, 160 patients had DM at the time of diagnosis of APC (remote-onset, 87; recent-onset, 73) and the remaining 23 patients developed DM during treatment of APC. Ultimately, 73.2% of patients (134/183) with DM received antidiabetic medication, including metformin (56 patients, 41.8%), sulfonylurea (62, 45.5%), and insulin (43, 32.1%). In multivariate analysis, cancer extent (hazard ratio [HR], 1.792; 95% confidence interval [CI], 1.313 to 2.445; p < 0.001) showed association with decreased overall survival (OS), whereas a diagnosis of DM (HR, 0.788; 95% CI, 0.615 to 1.009; p=0.059) conferred positive tendency on the OS. Metformin treatment itself conferred better OS in comparison within DM patients (HR 0.693; 95% CI, 0.492 to 0.977; p=0.036) and even in all APC patients (adjusted HR, 0.697; 95% CI, 0.491 to 1.990; p=0.044).
CONCLUSION
For APC patients receiving palliative chemotherapy, metformin treatment is associated with longer OS. Patients with DM tend to survive longer than those without DM.

Keyword

Pancreatic neoplasms; Prognosis; Antineoplastic agents; Diabetes mellitus; Metformin

MeSH Terms

Antineoplastic Agents
Diabetes Mellitus*
Diagnosis
Drug Therapy*
Heart
Humans
Insulin
Metformin*
Multivariate Analysis
Pancreatic Neoplasms*
Prognosis
Retrospective Studies
Antineoplastic Agents
Insulin
Metformin

Figure

• 

  Fig. 1. Overall survival (OS) of all patients by diabetes mellitus (DM) status. Kaplan-Meier estimates, demonstrating positive association between DM and OS (hazard ratio, 0.793; 95% confidence interval, 0.635 to 0.990; p=0.041, log-rank test). mOS, median OS.

• 

  Fig. 2. Overall survival of diabetes mellitus (DM) patients. (A) Recent-onset DM, not having significantly prolonged overall survival (OS) (vs. other DM subsets, including remote-onset DM and subsequent DM; hazard ratio [HR], 0.789; 95% confidence interval [CI], 0.574 to 1.083; p=0.142). (B) OS prolongation in metformin recipients vs non-recipients (HR, 0.693; 95% CI, 0.492 to 0.977; p=0.036). mOS, median OS.

• 

  Fig. 3. Overall survival (OS) of all patients by metformin. (A) OS (all patients) by metformin. Prolonged OS in metformin recipients versus non-recipients (hazard ratio [HR], 0.695; 95% confidence interval [CI], 0.509 to 0.948; p=0.022) (adjusted HR with performance, cancer extent, and weight loss [change in body mass index ≥ 1] during first-line therapy, 0.697; 95% CI, 0.491 to 0.990; p=0.044). (B) OS of diabetes mellitus (DM) treated with metformin surpassed that of other groups (non-DM or DM without metformin; p=0.029).

Reference

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