Diabetes Medication Use and Common Eye Disorders

In this podcast, Joëlle E. Vergroesen, MSc, discusses the results of her team's study examining how the use of metformin, insulin, and sulfonylurea derivatives may impact the risk of open-angle glaucoma, age-related macular degeneration (AMD), and cataracts among individuals with type 2 diabetes. 

Additional resource:

• Vergroesen JE, Thee EF, Ahmadizar F, et al. Association of diabetes medication with open-angle glaucoma, age-related macular degeneration, and cataract in the Rotterdam study. JAMA Ophthalmol. 2022;140(7):674-681. doi:10.1001/jamaophthalmol.2022.1435. 

Joëlle E. Vergroesen, MsC, is a PhD candidate at Erasmus University Medical Center in Rotterdam, Netherlands.

TRANSCRIPTION: 

Leigh Precopio: Hello everyone and welcome to another installment of Podcasts360, your go-to resource for medical education and clinical updates. I'm your moderator, Leigh Precopio with Consultant360, a multidisciplinary medical information network.

While previous literature has examined the impact that type 2 diabetes has on an individual’s eye health, the role that diabetic medication use may have on this relationship is significantly less understood.

To further our understanding, researchers conducted a cohort study based in Rotterdam in the Netherlands which examined the use of metformin, insulin, and sulfonylurea derivatives on the risk for open-angle glaucoma, age-related macular degeneration, and cataracts in individuals with type 2 diabetes.

I’m joined today by Joëlle E. Vergroesen, who is a PhD candidate at Erasmus University Medical Center and a contributing author of the study, to discuss the study results and areas for future research.

Thanks so much for joining me today. To begin, could you discuss the knowledge gaps you were hoping to bridge with this study?

Joëlle E. Vergroesen, MsC: So we were intrigued by the first results that anti-diabetic medications such as metformin could protect against open angle glaucoma and AMD. For open angle glaucoma, only one paper suggested this association, so there was a need of validation of these findings. For AMD, a few papers provided evidence for a protective effect of metformin on AMD. However, those studies were often cross-sectional and therefore they could not address causality.

Also, most studies did not assess the association between AMD and diabetes mellitus type 2. So they also did not take into account the severity of the diabetes when assessing the association between the diabetic medications and AMD. Therefore, they could not rule out the confounding by indication.

So we tried to overcome these knowledge gaps or these difficulties of other studies by using our prospective population-based cohort study in Rotterdam. We just aimed to first assess the association between untreated diabetes and the incidence of these age-related eye diseases. By doing so we could determine the effect of untreated diabetes on age-related eye diseases in our population specifically. These results added to the discussion if untreated diabetes should be considered a risk factor for open angle glaucoma, and it showed evidence that untreated diabetes is indeed a risk factor for AMD and cataract.

Once we establish this association, we knew we had to consider the potential confounding by indication effect of diabetes when assessing the association between these anti-diabetic medications and age-related eye diseases. More severe diabetes would potentially increase the risk of these age-related eye diseases and severe diabetes would potentially be treated with certain anti-diabetic medications or a combination of these medications. So if we would find a risk increasing effect of these medications, this could have been caused by the presence of diabetes itself rather than the medication use.

Therefore, we adjusted all our analysis for serum glucose levels as well, indicating whether diabetes control was sufficient, yes or no. And then, lastly, since we use the data of this prospective population-based cohort study in Rotterdam we were able to calculate also the cumulative lifetime risks. That was something that was not done before and showed that the risk is decreasing effect of anti-diabetic medications on open angle glaucoma and AMD. Most interestingly, some of these risks were even lower than the risk of age-related eye diseases in a healthy, non-diabetic population, indicating that metformin may have beneficial effects beyond glucose control.

Leigh Precopio: The results of your study revealed that the use of metformin and other diabetes medications were associated with lower risks of open-angle glaucoma and age-related macular degeneration, but no association was observed between these medications and the risk of cataracts. Is this a result that surprised you? Why or why not?

Joëlle Vergroesen: We first confirmed the well-known association between untreated diabetes and cataract. However, we did not find a significant protective effect of anti-diabetic medications for cataract. This to us was not surprising, since another study also was not able to find a protective effect. We believe that the association between diabetes and cataract may be so strong that sufficient treatment of diabetes can lower your risk of developing cataract only to some extent. Moreover, the lifetime risk of cataract in a healthy population is already around 85%, if we look at the age of 85, so the chance of developing cataract, despite having untreated or treated diabetes, is most likely to be similar.

Leigh Precopio: Could you discuss any other risk factors that may put individuals with type 2 diabetes who are on these medications at lower risk for developing these eye conditions?

Joëlle Vergroesen: We adjusted for many potential confounders, including age, sex, body mass index, the treatment with statins, and treatment with anti-hypertensive medications. We did so because in general, people with diabetes have a worse lifestyle and worse health profile. So, therefore, they may also suffer from high cholesterol levels or hypertension. In this study it is therefore unlikely that there are any other risk factors that would explain this association between untreated diabetes and age-related eye diseases, although it is possible that we did not control for all possible confounders, such as diet and physical activity.

Leigh Precopio: Your study included European individuals with type 2 diabetes. What aspects of the study results are generalizable to patients in the US?

Joëlle Vergroesen: The percentage of European individuals in our population was indeed high. It was about 98%, and this makes it difficult to directly translate our findings to people from other ethnicities. In the US specifically, the number of individuals from other ethnicities, such as the African ethnicity, are higher. And it's also known that these individuals have higher risk of open angle glaucoma but also a higher risk of diabetes and hypertension. It is also possible that their treatment for diabetes and hypertension is different and may be more aggressive than in individuals from European descent. So, although we try to adjust for these confounders, it is possible that our results are not directly translatable to non-European individuals.

Leigh Precopio: What knowledge gaps remain on the topic of diabetes medication use and common eye disorders among individuals with type 2 diabetes?

Joëlle Vergroesen: So we believe that our findings alongside the findings of other research groups show that the receiving treatment for type 2 diabetes is highly important. Not only have non-treated individuals a higher risk of age-related eye diseases, but when treated they can actually lower their lifetime risk of these age-related eye diseases below the risk of non-diabetic persons.

Since our publication, several other studies have shown a protective effect of metformin on AMD. For open angle glaucoma, however, confirmation of the results is still required. Preferably we would use a randomized clinical trial as this could also confirm the causality. Nevertheless, there are several hurdles to such an interventional trial, including the safety of treating non-diabetics with diabetes medications and the ethical concerns of randomizing patients for treatment vs no treatment. So it may well be that for this particular topic the highest level of evidence for safe and ethical investigation is the setting that we currently use.

That said our research only focused on the use of metformin, sulfonylurea, and insulin. Other anti-diabetics have emerged over the past decade so future study should also confirm our findings, but also aim to include a broader range of diabetes medications, such as sodium glucose cotransporter-2 inhibitors and glucagon like peptide 1 receptor agonists, because these may also be protective for certain age-related eye diseases.

Leigh Precopio: Thank you for taking the time to join me today.

Joëlle Vergroesen: Thank you for your interest in our study, and happy to discuss this with you.