6-month carcinogenicity study in transgenic mice, there was no
tumorigenic response. In a 2‑year carcinogenicity study
in rats, at ≥ 7 times the human clinical exposure following
1.5 mg dulaglutide per week, dulaglutide caused statistically
significant, dose‑related increases in the incidence of thyroid
C‑cell tumours (adenomas and carcinomas combined). The clinical
relevance of these findings is currently unknown.1
peptide-1 receptor agonists have induced thyroid C-cell adenomas and
carcinomas in mice and rats at clinically relevant exposures.
Dulagutide causes a dose-related and
treatment-duration-dependent increase in the incidence of thyroid
C-cell tumors, such as adenomas and carcinomas, in rats after
finding was not replicated in a 6-month carcinogenicity study in
rasH2 transgenic mice, nor in a 12-month study in monkeys.2,3
data reveal no special hazards for humans based on conventional
studies of safety pharmacology or repeat‑dose toxicity.1
was no increased reporting of potential C-cell hyperplasia in
dulaglutide-treated patients compared with placebo- or
has been 1 report of MTC in a patient who received dulaglutide 2 mg
for approximately 6 months in a study that was ongoing before the
implementation of exclusion criteria and serial calcitonin
monitoring. This cancer was assessed and determined to be
for rare diseases, like many cancers with long latency periods, the
database is too small and duration of exposure too short to
definitively conclude that there is no increased risk of malignancy.
Eli Lilly and Company will continue to carefully assess for
malignancies in ongoing studies and will continue to assess risk
through postmarketing cases and exposure.4
= Medullary Thyroid Carcinoma
Trulicity [summary of product characteristics]. Eli Lilly Nederland
B.V., The Netherlands.
Byrd RA, Sorden SD, Ryan T, et al. Chronic toxicity and
carcinogenicity studies of the long-acting GLP-1 receptor agonist
dulaglutide in rodents. Endocrinology. 2015;156(7):2417-2428.
Vahle JL, Byrd RA, Blackbourne JL, et al. Effects of dulaglutide on
thyroid C cells and serum calcitonin in male monkeys. Endocrinology.
Data on file, Eli Lilly and Company and/or one of its subsidiaries.
Skrivanek Z, Gaydos BL, Chien JY, et al. Dose-finding results in an
adaptive, seamless, randomized trial of once-weekly dulaglutide
combined with metformin in type 2 diabetes patients (AWARD-5).
Diabetes Obes Metab. 2014;16(8):748-756.
Sherman SI, Kloos RT, Tuttle RM, et al. No calcitonin change in a
person taking dulaglutide diagnosed with pre-existing medullary
thyroid cancer [published online July 29, 2017]. Diabet Med.