Trulicity® (dulaglutide): Retinopathy

Detailed Information

During both clinical studies and standard postmarketing pharmacovigilance activities, retinopathy and retinopathy-related complications were collected as

• spontaneously reported medical history

• adverse events, or 

• a component of a secondary endpoint in a CV outcomes trial.¹

In 6 placebo- and active-controlled studies, retinopathy was reported in

• 5.2% of the population at baseline, and

• less than 1% of patients as a treatment-emergent adverse event.²

Diabetic retinopathy is a leading cause of vision loss globally.³

Among people with DM, the overall worldwide prevalence is approximately

• 35% for any diabetic retinopathy, and

• 7% for proliferative diabetic retinopathy.⁴

The risk of diabetic retinopathy increases with

• longer duration of DM

• higher HbA1c levels, and

• presence of hypertension.³

Severity of diabetic retinopathy can range from asymptomatic changes in nonproliferative retinopathy detectable only by ophthalmological exams to vision-threatening sequelae associated with proliferative retinopathy and diabetic macular edema.³

Retinopathy in the REWIND Study

In the REWIND CV outcomes trial, diabetic retinopathy events were collected as 

• an AE, and

• a prespecified secondary composite endpoint.¹

For the secondary composite endpoint, REWIND prospectively collected events of diabetic retinopathy requiring

• photocoagulation

• antivascular endothelial growth factor therapy, or

• vitrectomy¹

Although numerically more events occurred in patients treated with Trulicity 1.5 mg compared to the placebo group, the risk difference was not statistically significant between groups.¹

The incidence of the eye outcome was

• 0.37 per 100 person-years for those assigned to dulaglutide, and

• 0.30 per 100 person-years for placebo (HR, 1.24; 95% CI, 0.92-1.68 ).¹

Eli Lilly and Company continues to monitor retinopathy reports through routine pharmacovigilance.

Retinopathy in the AWARD-11 Trial

The AWARD-11 trial was a phase 3, randomized, double-blind, active-controlled, parallel-arm study that assessed the efficacy and safety of dulaglutide 3.0 mg and dulaglutide 4.5 mg compared to dulaglutide 1.5 mg in patients with inadequately controlled T2DM on concomitant metformin therapy.⁵

There was no difference in the number of patients reporting retinopathy-related or other eye disorders between the dulaglutide 1.5 mg, dulaglutide 3.0 mg, and dulaglutide 4.5 mg treatment groups.²

All safety findings for the AWARD-11 trial were similar across the elderly patient population, ≥ 65 years old, when compared to the general patient population.²

Eli Lilly and Company continues to monitor retinopathy reports through routine pharmacovigilance.

References

1. Gerstein HC, Colhoun HM, Dagenais GR, et al; REWIND Investigators. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet. 2019;394(10193):121-130. https://doi.org/10.1016/S0140-6736(19)31149-3

2. Data on file, Eli Lilly and Company and/or one of its subsidiaries.

3. Stitt AW, Curtis TM, Chen M, et al. The progress in understanding and treatment of diabetic retinopathy. Prog Retin Eye Res. 2016;51:156-186. http://dx.doi.org/10.1016/j.preteyeres.2015.08.001

4. Yau JW, Rogers SL, Kawasaki R, et al. Meta-Analysis for Eye Disease (META-EYE) Study Group. Global prevalence and major risk factors of diabetic retinopathy. Diabetes Care. 2012;35(3):556-564. http://dx.doi.org/10.2337/dc11-1909

5. Frias JP, Nevárez Ruiz L, Li YG, et al. Efficacy and safety of higher dulaglutide doses (3.0 mg and 4.5 mg) when added to metformin in patients with type 2 diabetes: a phase 3, randomized, double-blind, parallel arm study (AWARD-11). J Endocr Soc. 2020;4(suppl 1):A1036. Endocrine Society abstract OR26-08. https://doi.org/10.1210/jendso/bvaa046.2057

Glossary

AE = adverse event

AWARD = Assessment of Weekly AdministRation of LY2189265 in Diabetes

CV = cardiovascular

DM = diabetes mellitus

GLP-1 RA = glucagon-like peptide-1 receptor agonist

HbA1c = glycated hemoglobin

HR = hazard ratio

REWIND = Researching cardiovascular Events with a Weekly INcretin in Diabetes