P2380 - Diabetes and Metformin Use in Association With Survival in Esophageal Cancer

Qiao-Li Wang, MD, PhD
Karolinska Institutet, Stockholm, Stockholms Lan, Sweden

Introduction: Diabetes is common among the elderly population and associated with an increased risk of mortality from some cancers. The antidiabetic medication metformin has anti-cancer properties and decreases the risk of developing esophageal cancer. However, it is unclear if diabetes worsens survival and whether metformin use improves survival in esophageal cancer.

Methods: This nationwide population-based cohort study included all patients with a newly diagnosed esophageal cancer during 2006-2018 in Sweden with follow-up through 2019. Diabetes and metformin use was analyzed in relation to risk of all-cause and disease-specific mortality using multivariable Cox regression. The hazard ratios (HR) with 95% confidence intervals (CI) were adjusted for age, sex, calendar year, obesity, comorbidity, and use of non-steroidal anti-inflammatory drugs or statins. For comparison reasons, three other antidiabetic medications were also analyzed, i.e., sulfonylureas, insulin, and thiazolidinedione. Dose-response associations were assessed and to avoid immortal time bias, the landmark method was used. Stratified analyses and sensitivity analyses were further applied. All the analyses followed a pre-defined protocol.

Results: Among 4851 incident esophageal cancer patients (8404 person-years), 4072 (84%) died during follow-up. Compared with esophageal cancer patients with diabetes but not using metformin, decreased all-cause mortality was found among non-diabetic patients (without metformin) (HR 0.86, 95% CI 0.77-0.96) and diabetic patients who used metformin (HR 0.86, 95% CI 0.75-1.00). The HRs of all-cause mortality decreased with a higher daily dose of metformin (p for trend 0.043). The corresponding risk estimates for disease-specific mortality were similar but slightly attenuated. The results were also similar in separate analyses of esophageal cancer patients with adenocarcinoma or squamous cell carcinoma, with tumor stage I-II or III-IV, and in those who had or had not undergone surgery. No associations with mortality outcomes were found for the use of sulfonylureas, insulin, or thiazolidinedione.

Discussion: Diabetes increases the risk of mortality among esophageal cancer patients. Use of metformin was instead associated with improved survival and the beneficial association had a dose-dependent appearance. But use of other antidiabetic medications did not influence mortality.

Table 1. Risk of disease-specific and all-cause mortality among esophageal cancer patients by diabetes status and metformin use
	Person-years	Disease-specific death	All-cause death	Disease-specific mortality			All-cause mortality
				Crude HR (95%CI)	Adjusted HR (95%CI)a		Crude HR (95%CI)	Adjusted HR (95%CI)a
Diabetes status
Diabetes without metformin	508	269	344	1.00 (Reference))	1.00 (Reference)		1.00 (Reference)	1.00 (Reference)
No Diabetes	7122	2723	3350	0.78 (0.69-0.89)	0.91 (0.80-1.03)		0.75 (0.67-0.83)	0.86 (0.77-0.96)
Metformin use
No metformin	508	269	344	1.00 (Reference)	1.00 (Reference)		1.00 (Reference)	1.00 (Reference)
Any dose metformin	774	295	378	0.72 (0.61-0.85)	0.90 (0.76-1.07)		0.72 (0.62-0.83)	0.86 (0.75-1.00)
< 150 DDD	233	92	111	0.80 (0.63-1.01)	0.92 (0.72-1.17)		0.74 (0.60-0.92)	0.83 (0.66-1.03)
150-299 DDD	223	96	128	0.76 (0.60-0.96)	0.92 (0.73-1.17)		0.80 (0.65-0.98)	0.94 (0.76-1.15)
≥300 DDD	317	107	139	0.64 (0.52-0.81)	0.80 (0.63-1.01)		0.65 (0.53-0.79)	0.78 (0.64-0.96)
P for trendb	/	/	/	< 0.001	0.067		< 0.001	0.043
a Model adjusted for age, sex, calendar year, obesity, comorbidity, and other medications (non-steroidal anti-inflammatory drugs or statin) b Modeled by taking the mean of the DDD quantity as 0, 75, 203, and 403 DDD Abbreviation: HR, hazard ratio; CI, confidence interval; DDD, defined daily dose

Disclosures:
Qiao-Li Wang indicated no relevant financial relationships.


Qiao-Li Wang, MD, PhD. P2380 - Diabetes and Metformin Use in Association With Survival in Esophageal Cancer, ACG 2021 Annual Scientific Meeting Abstracts. Las Vegas, Nevada: American College of Gastroenterology.