Antidiabetic Treatment in Patients at High Risk for a Subsequent Keratinocyte Carcinoma

May 2022 | Volume 21 | Issue 5 | Original Article | 502 | Copyright © May 2022


Published online April 22, 2022

Angelica Misitzis MD,a,b,c Alexander J. Stratigos MD PhD,c George Mastorakos MD PhD,c Martin A. Weinstock MD PhDa,b for the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial Group

ªCenter for Dermatoepidemiology, Providence VA Medical Center, Providence, RI
bDepartment of Dermatology, Brown University, Providence, RI
c1st Department of Dermatology and Venereology, National and Kapodistrian University of Athens, Athens, Greece
dUnit of Endocrinology, Diabetes mellitus and Metabolism, 2nd Department of Obstetrics and Gynecology,
National and Kapodistrian University of Athens, Athens, Greece

Abstract
Background: Metformin and sulfonylureas are the most commonly prescribed drugs used for the treatment of type II diabetes. Type II diabetes has been linked to the development of keratinocyte carcinoma (KC), consisting of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Previously we have demonstrated lower risk for a subsequent KC in metformin users. In this study, we aim to investigate the association between sulfonylureas use and the development of KC in patients with KC history. We performed a retrospective cohort study of the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial, which was a randomized double-blind vehicle-control cream originally investigating the effect of 5-fluorouracil on KC development. 932 patients with a history of KC were enrolled (98% male, 99% white, median age of 70 years) and followed for a median duration of 2.8 years. 153 patients were on metformin and 94 on sulfonylureas. We performed a survival analysis with cox regression and controlled for body mass index and known predictors: number of prior BCCs and age (for BCC) and for number of prior SCCs (invasive and in situ), number of actinic keratoses at baseline (for SCC). Sulfonylurea-users com-pared to non-users had a HR of 0.67 (CI: 0.40–1.56; P=0.49) and 0.94 (CI: 0.63–1.40; P= 0.77), for SCC and BCC, respectively. Diabetic patients at high risk for KC might benefit from the use of metformin versus sulfonylureas.

J Drugs Dermatol. 2022;21(5):502-505. doi:10.36849/JDD.6087

INTRODUCTION

Diabetes is one of the leading causes of death and disability in the United States, with an estimated global prevalence of 9.3% in 2019.1,2 The development of skin cancer is associated with type 2 diabetes (T2D).3 Keratinocyte carcinoma (KC), which includes basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), incidence and mortality are increasing.4 Metformin the most commonly prescribed drug for T2D has been linked to reduced cancer incidence, including KC.3,5,6 On the contrary, sulfonylurea use has not been associated with solid cancer development, however, there are studies that showed an increase in all-cancer risk with sulfonylurea use.7,8

Previously, we have demonstrated decreased risk for a subsequent KC for metformin users versus non-users.6 In this article, we aim to study the association of sulfonylureas with the development of KC in the same cohort.

MATERIALS AND METHODS

Study Design
We performed a secondary analysis of the cohort enrolled in the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial (VAKCC).9 Drug use data were derived from the Pharmacy Benefits Management program of the Veterans Health Administration.

Setting
The VAKCC (Cooperative Studies Program [CSP] 562) was a double-blind, vehicle-control cream trial investigating the chemoprotective effect of 5 fluorouracil (5FU) on the development of KC.

Participants were randomized to apply topical 5FU or vehicle control cream twice a day to the face and ears for up to 4 weeks (56 doses in total).

The primary endpoint was ascertained either at a semi-annual scheduled follow-up study examination or at an examination requested by the patient. Biopsies were obtained from clinically suspicious lesions from the face and ears and corre-sponding reports were read by the study’s dermatopathologist
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