NANOSNET

Hi Dr NS,

Answers to your questions from the Danish study (Grauslund, J., Taha, A.A., Molander, L.D. et al. Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes. Int J Retin Vitr 10, 97 (2024). )

The answers sound very logical, but nobody wants to knowingly lose vision, whatever the advantages of the drug are.

1. I am curious what the conversations are with your patients. Diabetics with disk at risk, should they avoid ever taking the medication?If a patient experiences NAION do you automatically advise to discontinue the medication?
   "Even though we have demonstrated a higher risk of NAION in persons with T2D exposed to once-weekly semaglutide, it is important to keep in mind that use of semaglutide comes with substantial advantages for patients as given by the improved glycemic control, reduction in risk of cardiovascular disease as well as the beneficial effects of weight loss [1]. As such, the observed incidence rate of NAION of 0·228 per 1000 person-years for persons with T2D exposed with once-weekly semaglutide may not discourage semaglutide treatment but needs to be acknowledged as a potential risk."
2. Also, interested in the mechanism of how the medication reduces perfusion to the nerve.
   "As the pathogenic pathway of NAION is insufficiently understood, it is difficult to speculate as to how semaglutide may lead to elevated risk. Expression of glucagon-like peptide-1 receptor agonist receptors have been identified in the optic nerve [20], but it is unknown whether continuous stimulation of these with specific glucagon-like peptide-1 receptor agonists may alter vascular perfusion of the optic nerve head. In SUSTAIN-6, use of once-weekly semaglutide led to an increased risk of diabetic retinopathy worsening (HR 1·76, 95% CI 1·11 − 2·76) [1], and it has been speculated that this can likely be attributed to early worsening given the rapid improvement in glycemic control in the semaglutide arm [21]. While persons exposed to semaglutide in our study also had impaired glycemic control (hemoglobin A1c 54 vs. 49 mmol/mol in non-exposed group), our findings of an increased risk of NAION were still statistically significant after adjustment for glycemic control, indicating a likely different mode of action as in diabetic retinopathy."

Hope this helps!

Gooday everyone!

Hello,

To address the question on what the conversation I have:  I share with them that correlation does not mean causation.  The patients on semiglutides at the beginning were the patients who were needing it for other health reasons (we cherry picked the patients with the most amount of risks for microvascular disease and had diabetes) at the beginning.  Long before semiglutides, diabetes was a known risk factor for NAION.  I tell them after examining the nerve if they had disc at risk and whether they may have had inborn additional inherit risks. The AAO/NANOS joint statement does not advise stoppage.  I generally advise against large metabolic swings when controlling DM and achieving weight loss and try to identify the other risk factors, putting my focus on the disease itself rather than blaming the medicine.  I usually recommend continued weigh loss whether with semiglutide or not because of the long term health effects of their poor control of X.  

To address Marilyn's comment regarding a simpler link to Larry's attachment:  via email you can click the attachment, but anything linked to NANOS will prompt you to login....  Just like the old days.  It is actually now easier to share attachments than before.  (See my attached screenshot).  The new platform we are all learning the shortcuts to make it easier to navigate...

Best,

Barbara

Hi Dr NS,

Answers to your questions from the Danish study (Grauslund, J., Taha, A.A., Molander, L.D. et al. Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes. Int J Retin Vitr 10, 97 (2024). )

The answers sound very logical, but nobody wants to knowingly lose vision, whatever the advantages of the drug are.

1. I am curious what the conversations are with your patients. Diabetics with disk at risk, should they avoid ever taking the medication?If a patient experiences NAION do you automatically advise to discontinue the medication?
   "Even though we have demonstrated a higher risk of NAION in persons with T2D exposed to once-weekly semaglutide, it is important to keep in mind that use of semaglutide comes with substantial advantages for patients as given by the improved glycemic control, reduction in risk of cardiovascular disease as well as the beneficial effects of weight loss [1]. As such, the observed incidence rate of NAION of 0·228 per 1000 person-years for persons with T2D exposed with once-weekly semaglutide may not discourage semaglutide treatment but needs to be acknowledged as a potential risk."
2. Also, interested in the mechanism of how the medication reduces perfusion to the nerve.
   "As the pathogenic pathway of NAION is insufficiently understood, it is difficult to speculate as to how semaglutide may lead to elevated risk. Expression of glucagon-like peptide-1 receptor agonist receptors have been identified in the optic nerve [20], but it is unknown whether continuous stimulation of these with specific glucagon-like peptide-1 receptor agonists may alter vascular perfusion of the optic nerve head. In SUSTAIN-6, use of once-weekly semaglutide led to an increased risk of diabetic retinopathy worsening (HR 1·76, 95% CI 1·11 − 2·76) [1], and it has been speculated that this can likely be attributed to early worsening given the rapid improvement in glycemic control in the semaglutide arm [21]. While persons exposed to semaglutide in our study also had impaired glycemic control (hemoglobin A1c 54 vs. 49 mmol/mol in non-exposed group), our findings of an increased risk of NAION were still statistically significant after adjustment for glycemic control, indicating a likely different mode of action as in diabetic retinopathy."

Hope this helps!

Gooday everyone!

Hello,

thanks for all the inputs so far. Based on the current data, it seems reasonable not to advise discontinuation of GLP-1RA in general. However, what should we tell patients with NAION in one eye and disc at risk in the fellow eye?

Hello,

To address the question on what the conversation I have:  I share with them that correlation does not mean causation.  The patients on semiglutides at the beginning were the patients who were needing it for other health reasons (we cherry picked the patients with the most amount of risks for microvascular disease and had diabetes) at the beginning.  Long before semiglutides, diabetes was a known risk factor for NAION.  I tell them after examining the nerve if they had disc at risk and whether they may have had inborn additional inherit risks. The AAO/NANOS joint statement does not advise stoppage.  I generally advise against large metabolic swings when controlling DM and achieving weight loss and try to identify the other risk factors, putting my focus on the disease itself rather than blaming the medicine.  I usually recommend continued weigh loss whether with semiglutide or not because of the long term health effects of their poor control of X.  

To address Marilyn's comment regarding a simpler link to Larry's attachment:  via email you can click the attachment, but anything linked to NANOS will prompt you to login....  Just like the old days.  It is actually now easier to share attachments than before.  (See my attached screenshot).  The new platform we are all learning the shortcuts to make it easier to navigate...

Best,

Barbara

Hi Dr NS,

Answers to your questions from the Danish study (Grauslund, J., Taha, A.A., Molander, L.D. et al. Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes. Int J Retin Vitr 10, 97 (2024). )

The answers sound very logical, but nobody wants to knowingly lose vision, whatever the advantages of the drug are.

1. I am curious what the conversations are with your patients. Diabetics with disk at risk, should they avoid ever taking the medication?If a patient experiences NAION do you automatically advise to discontinue the medication?
   "Even though we have demonstrated a higher risk of NAION in persons with T2D exposed to once-weekly semaglutide, it is important to keep in mind that use of semaglutide comes with substantial advantages for patients as given by the improved glycemic control, reduction in risk of cardiovascular disease as well as the beneficial effects of weight loss [1]. As such, the observed incidence rate of NAION of 0·228 per 1000 person-years for persons with T2D exposed with once-weekly semaglutide may not discourage semaglutide treatment but needs to be acknowledged as a potential risk."
2. Also, interested in the mechanism of how the medication reduces perfusion to the nerve.
   "As the pathogenic pathway of NAION is insufficiently understood, it is difficult to speculate as to how semaglutide may lead to elevated risk. Expression of glucagon-like peptide-1 receptor agonist receptors have been identified in the optic nerve [20], but it is unknown whether continuous stimulation of these with specific glucagon-like peptide-1 receptor agonists may alter vascular perfusion of the optic nerve head. In SUSTAIN-6, use of once-weekly semaglutide led to an increased risk of diabetic retinopathy worsening (HR 1·76, 95% CI 1·11 − 2·76) [1], and it has been speculated that this can likely be attributed to early worsening given the rapid improvement in glycemic control in the semaglutide arm [21]. While persons exposed to semaglutide in our study also had impaired glycemic control (hemoglobin A1c 54 vs. 49 mmol/mol in non-exposed group), our findings of an increased risk of NAION were still statistically significant after adjustment for glycemic control, indicating a likely different mode of action as in diabetic retinopathy."

Hope this helps!

Gooday everyone!

Hello,

thanks for all the inputs so far. Based on the current data, it seems reasonable not to advise discontinuation of GLP-1RA in general. However, what should we tell patients with NAION in one eye and disc at risk in the fellow eye?

Hello,

To address the question on what the conversation I have:  I share with them that correlation does not mean causation.  The patients on semiglutides at the beginning were the patients who were needing it for other health reasons (we cherry picked the patients with the most amount of risks for microvascular disease and had diabetes) at the beginning.  Long before semiglutides, diabetes was a known risk factor for NAION.  I tell them after examining the nerve if they had disc at risk and whether they may have had inborn additional inherit risks. The AAO/NANOS joint statement does not advise stoppage.  I generally advise against large metabolic swings when controlling DM and achieving weight loss and try to identify the other risk factors, putting my focus on the disease itself rather than blaming the medicine.  I usually recommend continued weigh loss whether with semiglutide or not because of the long term health effects of their poor control of X.  

To address Marilyn's comment regarding a simpler link to Larry's attachment:  via email you can click the attachment, but anything linked to NANOS will prompt you to login....  Just like the old days.  It is actually now easier to share attachments than before.  (See my attached screenshot).  The new platform we are all learning the shortcuts to make it easier to navigate...

Best,

Barbara

Hi Dr NS,

Answers to your questions from the Danish study (Grauslund, J., Taha, A.A., Molander, L.D. et al. Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes. Int J Retin Vitr 10, 97 (2024). )

The answers sound very logical, but nobody wants to knowingly lose vision, whatever the advantages of the drug are.

1. I am curious what the conversations are with your patients. Diabetics with disk at risk, should they avoid ever taking the medication?If a patient experiences NAION do you automatically advise to discontinue the medication?
   "Even though we have demonstrated a higher risk of NAION in persons with T2D exposed to once-weekly semaglutide, it is important to keep in mind that use of semaglutide comes with substantial advantages for patients as given by the improved glycemic control, reduction in risk of cardiovascular disease as well as the beneficial effects of weight loss [1]. As such, the observed incidence rate of NAION of 0·228 per 1000 person-years for persons with T2D exposed with once-weekly semaglutide may not discourage semaglutide treatment but needs to be acknowledged as a potential risk."
2. Also, interested in the mechanism of how the medication reduces perfusion to the nerve.
   "As the pathogenic pathway of NAION is insufficiently understood, it is difficult to speculate as to how semaglutide may lead to elevated risk. Expression of glucagon-like peptide-1 receptor agonist receptors have been identified in the optic nerve [20], but it is unknown whether continuous stimulation of these with specific glucagon-like peptide-1 receptor agonists may alter vascular perfusion of the optic nerve head. In SUSTAIN-6, use of once-weekly semaglutide led to an increased risk of diabetic retinopathy worsening (HR 1·76, 95% CI 1·11 − 2·76) [1], and it has been speculated that this can likely be attributed to early worsening given the rapid improvement in glycemic control in the semaglutide arm [21]. While persons exposed to semaglutide in our study also had impaired glycemic control (hemoglobin A1c 54 vs. 49 mmol/mol in non-exposed group), our findings of an increased risk of NAION were still statistically significant after adjustment for glycemic control, indicating a likely different mode of action as in diabetic retinopathy."

Hope this helps!

Gooday everyone!

Hello,

thanks for all the inputs so far. Based on the current data, it seems reasonable not to advise discontinuation of GLP-1RA in general. However, what should we tell patients with NAION in one eye and disc at risk in the fellow eye?

Hello,

To address the question on what the conversation I have:  I share with them that correlation does not mean causation.  The patients on semiglutides at the beginning were the patients who were needing it for other health reasons (we cherry picked the patients with the most amount of risks for microvascular disease and had diabetes) at the beginning.  Long before semiglutides, diabetes was a known risk factor for NAION.  I tell them after examining the nerve if they had disc at risk and whether they may have had inborn additional inherit risks. The AAO/NANOS joint statement does not advise stoppage.  I generally advise against large metabolic swings when controlling DM and achieving weight loss and try to identify the other risk factors, putting my focus on the disease itself rather than blaming the medicine.  I usually recommend continued weigh loss whether with semiglutide or not because of the long term health effects of their poor control of X.  

To address Marilyn's comment regarding a simpler link to Larry's attachment:  via email you can click the attachment, but anything linked to NANOS will prompt you to login....  Just like the old days.  It is actually now easier to share attachments than before.  (See my attached screenshot).  The new platform we are all learning the shortcuts to make it easier to navigate...

Best,

Barbara

Hi Dr NS,

Answers to your questions from the Danish study (Grauslund, J., Taha, A.A., Molander, L.D. et al. Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes. Int J Retin Vitr 10, 97 (2024). )

The answers sound very logical, but nobody wants to knowingly lose vision, whatever the advantages of the drug are.

1. I am curious what the conversations are with your patients. Diabetics with disk at risk, should they avoid ever taking the medication?If a patient experiences NAION do you automatically advise to discontinue the medication?
   "Even though we have demonstrated a higher risk of NAION in persons with T2D exposed to once-weekly semaglutide, it is important to keep in mind that use of semaglutide comes with substantial advantages for patients as given by the improved glycemic control, reduction in risk of cardiovascular disease as well as the beneficial effects of weight loss [1]. As such, the observed incidence rate of NAION of 0·228 per 1000 person-years for persons with T2D exposed with once-weekly semaglutide may not discourage semaglutide treatment but needs to be acknowledged as a potential risk."
2. Also, interested in the mechanism of how the medication reduces perfusion to the nerve.
   "As the pathogenic pathway of NAION is insufficiently understood, it is difficult to speculate as to how semaglutide may lead to elevated risk. Expression of glucagon-like peptide-1 receptor agonist receptors have been identified in the optic nerve [20], but it is unknown whether continuous stimulation of these with specific glucagon-like peptide-1 receptor agonists may alter vascular perfusion of the optic nerve head. In SUSTAIN-6, use of once-weekly semaglutide led to an increased risk of diabetic retinopathy worsening (HR 1·76, 95% CI 1·11 − 2·76) [1], and it has been speculated that this can likely be attributed to early worsening given the rapid improvement in glycemic control in the semaglutide arm [21]. While persons exposed to semaglutide in our study also had impaired glycemic control (hemoglobin A1c 54 vs. 49 mmol/mol in non-exposed group), our findings of an increased risk of NAION were still statistically significant after adjustment for glycemic control, indicating a likely different mode of action as in diabetic retinopathy."

Hope this helps!

Gooday everyone!

Hello,

thanks for all the inputs so far. Based on the current data, it seems reasonable not to advise discontinuation of GLP-1RA in general. However, what should we tell patients with NAION in one eye and disc at risk in the fellow eye?

Hello,

To address the question on what the conversation I have:  I share with them that correlation does not mean causation.  The patients on semiglutides at the beginning were the patients who were needing it for other health reasons (we cherry picked the patients with the most amount of risks for microvascular disease and had diabetes) at the beginning.  Long before semiglutides, diabetes was a known risk factor for NAION.  I tell them after examining the nerve if they had disc at risk and whether they may have had inborn additional inherit risks. The AAO/NANOS joint statement does not advise stoppage.  I generally advise against large metabolic swings when controlling DM and achieving weight loss and try to identify the other risk factors, putting my focus on the disease itself rather than blaming the medicine.  I usually recommend continued weigh loss whether with semiglutide or not because of the long term health effects of their poor control of X.  

To address Marilyn's comment regarding a simpler link to Larry's attachment:  via email you can click the attachment, but anything linked to NANOS will prompt you to login....  Just like the old days.  It is actually now easier to share attachments than before.  (See my attached screenshot).  The new platform we are all learning the shortcuts to make it easier to navigate...

Best,

Barbara

Hi Dr NS,

Answers to your questions from the Danish study (Grauslund, J., Taha, A.A., Molander, L.D. et al. Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes. Int J Retin Vitr 10, 97 (2024). )

The answers sound very logical, but nobody wants to knowingly lose vision, whatever the advantages of the drug are.

1. I am curious what the conversations are with your patients. Diabetics with disk at risk, should they avoid ever taking the medication?If a patient experiences NAION do you automatically advise to discontinue the medication?
   "Even though we have demonstrated a higher risk of NAION in persons with T2D exposed to once-weekly semaglutide, it is important to keep in mind that use of semaglutide comes with substantial advantages for patients as given by the improved glycemic control, reduction in risk of cardiovascular disease as well as the beneficial effects of weight loss [1]. As such, the observed incidence rate of NAION of 0·228 per 1000 person-years for persons with T2D exposed with once-weekly semaglutide may not discourage semaglutide treatment but needs to be acknowledged as a potential risk."
2. Also, interested in the mechanism of how the medication reduces perfusion to the nerve.
   "As the pathogenic pathway of NAION is insufficiently understood, it is difficult to speculate as to how semaglutide may lead to elevated risk. Expression of glucagon-like peptide-1 receptor agonist receptors have been identified in the optic nerve [20], but it is unknown whether continuous stimulation of these with specific glucagon-like peptide-1 receptor agonists may alter vascular perfusion of the optic nerve head. In SUSTAIN-6, use of once-weekly semaglutide led to an increased risk of diabetic retinopathy worsening (HR 1·76, 95% CI 1·11 − 2·76) [1], and it has been speculated that this can likely be attributed to early worsening given the rapid improvement in glycemic control in the semaglutide arm [21]. While persons exposed to semaglutide in our study also had impaired glycemic control (hemoglobin A1c 54 vs. 49 mmol/mol in non-exposed group), our findings of an increased risk of NAION were still statistically significant after adjustment for glycemic control, indicating a likely different mode of action as in diabetic retinopathy."

Hope this helps!

Gooday everyone!

Hello,

thanks for all the inputs so far. Based on the current data, it seems reasonable not to advise discontinuation of GLP-1RA in general. However, what should we tell patients with NAION in one eye and disc at risk in the fellow eye?

Hello,

To address the question on what the conversation I have:  I share with them that correlation does not mean causation.  The patients on semiglutides at the beginning were the patients who were needing it for other health reasons (we cherry picked the patients with the most amount of risks for microvascular disease and had diabetes) at the beginning.  Long before semiglutides, diabetes was a known risk factor for NAION.  I tell them after examining the nerve if they had disc at risk and whether they may have had inborn additional inherit risks. The AAO/NANOS joint statement does not advise stoppage.  I generally advise against large metabolic swings when controlling DM and achieving weight loss and try to identify the other risk factors, putting my focus on the disease itself rather than blaming the medicine.  I usually recommend continued weigh loss whether with semiglutide or not because of the long term health effects of their poor control of X.  

To address Marilyn's comment regarding a simpler link to Larry's attachment:  via email you can click the attachment, but anything linked to NANOS will prompt you to login....  Just like the old days.  It is actually now easier to share attachments than before.  (See my attached screenshot).  The new platform we are all learning the shortcuts to make it easier to navigate...

Best,

Barbara

Hi Dr NS,

Answers to your questions from the Danish study (Grauslund, J., Taha, A.A., Molander, L.D. et al. Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes. Int J Retin Vitr 10, 97 (2024). )

The answers sound very logical, but nobody wants to knowingly lose vision, whatever the advantages of the drug are.

1. I am curious what the conversations are with your patients. Diabetics with disk at risk, should they avoid ever taking the medication?If a patient experiences NAION do you automatically advise to discontinue the medication?
   "Even though we have demonstrated a higher risk of NAION in persons with T2D exposed to once-weekly semaglutide, it is important to keep in mind that use of semaglutide comes with substantial advantages for patients as given by the improved glycemic control, reduction in risk of cardiovascular disease as well as the beneficial effects of weight loss [1]. As such, the observed incidence rate of NAION of 0·228 per 1000 person-years for persons with T2D exposed with once-weekly semaglutide may not discourage semaglutide treatment but needs to be acknowledged as a potential risk."
2. Also, interested in the mechanism of how the medication reduces perfusion to the nerve.
   "As the pathogenic pathway of NAION is insufficiently understood, it is difficult to speculate as to how semaglutide may lead to elevated risk. Expression of glucagon-like peptide-1 receptor agonist receptors have been identified in the optic nerve [20], but it is unknown whether continuous stimulation of these with specific glucagon-like peptide-1 receptor agonists may alter vascular perfusion of the optic nerve head. In SUSTAIN-6, use of once-weekly semaglutide led to an increased risk of diabetic retinopathy worsening (HR 1·76, 95% CI 1·11 − 2·76) [1], and it has been speculated that this can likely be attributed to early worsening given the rapid improvement in glycemic control in the semaglutide arm [21]. While persons exposed to semaglutide in our study also had impaired glycemic control (hemoglobin A1c 54 vs. 49 mmol/mol in non-exposed group), our findings of an increased risk of NAION were still statistically significant after adjustment for glycemic control, indicating a likely different mode of action as in diabetic retinopathy."

Hope this helps!

Gooday everyone!

Another interesting piece of data to consider, but in Europe that are pushing to have NAION added to the label for these medications as a side effect:

PRAC concludes eye condition NAION is a very rare side effect of semaglutide medicines Ozempic, Rybelsus and Wegovy | European Medicines Agency (EMA)

In addition this was a very interesting abstract from Mass Eye and Ear presented recently at ARVO looking at the changes in retinal vasculature on OCTA in patients taking GLP vs. no GLP, and found a significant decrease in vasculature in GLP use. This may help point to the mechanism of why these patients get NAION (hopefully the link works, i'm sharing it directly from the ARVO app)

EventPilot

Personally, I tell my patients to stop taking it if they've had an event, and they are almost always on board. A lot of them have already stopped the medication before I see them because of their own research. There are plenty of other medications for diabetes. Not to mention there are some reports of the GLP's worsening diabetic retinopathy and now AMD…

https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2834964

Hope this helps!

Hello,

thanks for all the inputs so far. Based on the current data, it seems reasonable not to advise discontinuation of GLP-1RA in general. However, what should we tell patients with NAION in one eye and disc at risk in the fellow eye?

Hello,

To address the question on what the conversation I have:  I share with them that correlation does not mean causation.  The patients on semiglutides at the beginning were the patients who were needing it for other health reasons (we cherry picked the patients with the most amount of risks for microvascular disease and had diabetes) at the beginning.  Long before semiglutides, diabetes was a known risk factor for NAION.  I tell them after examining the nerve if they had disc at risk and whether they may have had inborn additional inherit risks. The AAO/NANOS joint statement does not advise stoppage.  I generally advise against large metabolic swings when controlling DM and achieving weight loss and try to identify the other risk factors, putting my focus on the disease itself rather than blaming the medicine.  I usually recommend continued weigh loss whether with semiglutide or not because of the long term health effects of their poor control of X.  

To address Marilyn's comment regarding a simpler link to Larry's attachment:  via email you can click the attachment, but anything linked to NANOS will prompt you to login....  Just like the old days.  It is actually now easier to share attachments than before.  (See my attached screenshot).  The new platform we are all learning the shortcuts to make it easier to navigate...

Best,

Barbara

Hi Dr NS,

Answers to your questions from the Danish study (Grauslund, J., Taha, A.A., Molander, L.D. et al. Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes. Int J Retin Vitr 10, 97 (2024). )

The answers sound very logical, but nobody wants to knowingly lose vision, whatever the advantages of the drug are.

1. I am curious what the conversations are with your patients. Diabetics with disk at risk, should they avoid ever taking the medication?If a patient experiences NAION do you automatically advise to discontinue the medication?
   "Even though we have demonstrated a higher risk of NAION in persons with T2D exposed to once-weekly semaglutide, it is important to keep in mind that use of semaglutide comes with substantial advantages for patients as given by the improved glycemic control, reduction in risk of cardiovascular disease as well as the beneficial effects of weight loss [1]. As such, the observed incidence rate of NAION of 0·228 per 1000 person-years for persons with T2D exposed with once-weekly semaglutide may not discourage semaglutide treatment but needs to be acknowledged as a potential risk."
2. Also, interested in the mechanism of how the medication reduces perfusion to the nerve.
   "As the pathogenic pathway of NAION is insufficiently understood, it is difficult to speculate as to how semaglutide may lead to elevated risk. Expression of glucagon-like peptide-1 receptor agonist receptors have been identified in the optic nerve [20], but it is unknown whether continuous stimulation of these with specific glucagon-like peptide-1 receptor agonists may alter vascular perfusion of the optic nerve head. In SUSTAIN-6, use of once-weekly semaglutide led to an increased risk of diabetic retinopathy worsening (HR 1·76, 95% CI 1·11 − 2·76) [1], and it has been speculated that this can likely be attributed to early worsening given the rapid improvement in glycemic control in the semaglutide arm [21]. While persons exposed to semaglutide in our study also had impaired glycemic control (hemoglobin A1c 54 vs. 49 mmol/mol in non-exposed group), our findings of an increased risk of NAION were still statistically significant after adjustment for glycemic control, indicating a likely different mode of action as in diabetic retinopathy."

Hope this helps!

Gooday everyone!

Another interesting piece of data to consider, but in Europe that are pushing to have NAION added to the label for these medications as a side effect:

PRAC concludes eye condition NAION is a very rare side effect of semaglutide medicines Ozempic, Rybelsus and Wegovy | European Medicines Agency (EMA)

In addition this was a very interesting abstract from Mass Eye and Ear presented recently at ARVO looking at the changes in retinal vasculature on OCTA in patients taking GLP vs. no GLP, and found a significant decrease in vasculature in GLP use. This may help point to the mechanism of why these patients get NAION (hopefully the link works, i'm sharing it directly from the ARVO app)

EventPilot

Personally, I tell my patients to stop taking it if they've had an event, and they are almost always on board. A lot of them have already stopped the medication before I see them because of their own research. There are plenty of other medications for diabetes. Not to mention there are some reports of the GLP's worsening diabetic retinopathy and now AMD…

https://jamanetwork.com/journals/jamaophthalmology/article-abstract/2834964

Hope this helps!

Hello,

thanks for all the inputs so far. Based on the current data, it seems reasonable not to advise discontinuation of GLP-1RA in general. However, what should we tell patients with NAION in one eye and disc at risk in the fellow eye?

Hello,

To address the question on what the conversation I have:  I share with them that correlation does not mean causation.  The patients on semiglutides at the beginning were the patients who were needing it for other health reasons (we cherry picked the patients with the most amount of risks for microvascular disease and had diabetes) at the beginning.  Long before semiglutides, diabetes was a known risk factor for NAION.  I tell them after examining the nerve if they had disc at risk and whether they may have had inborn additional inherit risks. The AAO/NANOS joint statement does not advise stoppage.  I generally advise against large metabolic swings when controlling DM and achieving weight loss and try to identify the other risk factors, putting my focus on the disease itself rather than blaming the medicine.  I usually recommend continued weigh loss whether with semiglutide or not because of the long term health effects of their poor control of X.  

To address Marilyn's comment regarding a simpler link to Larry's attachment:  via email you can click the attachment, but anything linked to NANOS will prompt you to login....  Just like the old days.  It is actually now easier to share attachments than before.  (See my attached screenshot).  The new platform we are all learning the shortcuts to make it easier to navigate...

Best,

Barbara

Hi Dr NS,

Answers to your questions from the Danish study (Grauslund, J., Taha, A.A., Molander, L.D. et al. Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes. Int J Retin Vitr 10, 97 (2024). )

The answers sound very logical, but nobody wants to knowingly lose vision, whatever the advantages of the drug are.

1. I am curious what the conversations are with your patients. Diabetics with disk at risk, should they avoid ever taking the medication?If a patient experiences NAION do you automatically advise to discontinue the medication?
   "Even though we have demonstrated a higher risk of NAION in persons with T2D exposed to once-weekly semaglutide, it is important to keep in mind that use of semaglutide comes with substantial advantages for patients as given by the improved glycemic control, reduction in risk of cardiovascular disease as well as the beneficial effects of weight loss [1]. As such, the observed incidence rate of NAION of 0·228 per 1000 person-years for persons with T2D exposed with once-weekly semaglutide may not discourage semaglutide treatment but needs to be acknowledged as a potential risk."
2. Also, interested in the mechanism of how the medication reduces perfusion to the nerve.
   "As the pathogenic pathway of NAION is insufficiently understood, it is difficult to speculate as to how semaglutide may lead to elevated risk. Expression of glucagon-like peptide-1 receptor agonist receptors have been identified in the optic nerve [20], but it is unknown whether continuous stimulation of these with specific glucagon-like peptide-1 receptor agonists may alter vascular perfusion of the optic nerve head. In SUSTAIN-6, use of once-weekly semaglutide led to an increased risk of diabetic retinopathy worsening (HR 1·76, 95% CI 1·11 − 2·76) [1], and it has been speculated that this can likely be attributed to early worsening given the rapid improvement in glycemic control in the semaglutide arm [21]. While persons exposed to semaglutide in our study also had impaired glycemic control (hemoglobin A1c 54 vs. 49 mmol/mol in non-exposed group), our findings of an increased risk of NAION were still statistically significant after adjustment for glycemic control, indicating a likely different mode of action as in diabetic retinopathy."

Hope this helps!

Gooday everyone!

Hi Dr NS,

Answers to your questions from the Danish study (Grauslund, J., Taha, A.A., Molander, L.D. et al. Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes. Int J Retin Vitr 10, 97 (2024). )

The answers sound very logical, but nobody wants to knowingly lose vision, whatever the advantages of the drug are.

1. I am curious what the conversations are with your patients. Diabetics with disk at risk, should they avoid ever taking the medication?If a patient experiences NAION do you automatically advise to discontinue the medication?
   "Even though we have demonstrated a higher risk of NAION in persons with T2D exposed to once-weekly semaglutide, it is important to keep in mind that use of semaglutide comes with substantial advantages for patients as given by the improved glycemic control, reduction in risk of cardiovascular disease as well as the beneficial effects of weight loss [1]. As such, the observed incidence rate of NAION of 0·228 per 1000 person-years for persons with T2D exposed with once-weekly semaglutide may not discourage semaglutide treatment but needs to be acknowledged as a potential risk."
2. Also, interested in the mechanism of how the medication reduces perfusion to the nerve.
   "As the pathogenic pathway of NAION is insufficiently understood, it is difficult to speculate as to how semaglutide may lead to elevated risk. Expression of glucagon-like peptide-1 receptor agonist receptors have been identified in the optic nerve [20], but it is unknown whether continuous stimulation of these with specific glucagon-like peptide-1 receptor agonists may alter vascular perfusion of the optic nerve head. In SUSTAIN-6, use of once-weekly semaglutide led to an increased risk of diabetic retinopathy worsening (HR 1·76, 95% CI 1·11 − 2·76) [1], and it has been speculated that this can likely be attributed to early worsening given the rapid improvement in glycemic control in the semaglutide arm [21]. While persons exposed to semaglutide in our study also had impaired glycemic control (hemoglobin A1c 54 vs. 49 mmol/mol in non-exposed group), our findings of an increased risk of NAION were still statistically significant after adjustment for glycemic control, indicating a likely different mode of action as in diabetic retinopathy."

Hope this helps!

Gooday everyone!

Hi Dr NS,

Answers to your questions from the Danish study (Grauslund, J., Taha, A.A., Molander, L.D. et al. Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes. Int J Retin Vitr 10, 97 (2024). )

The answers sound very logical, but nobody wants to knowingly lose vision, whatever the advantages of the drug are.

1. I am curious what the conversations are with your patients. Diabetics with disk at risk, should they avoid ever taking the medication?If a patient experiences NAION do you automatically advise to discontinue the medication?
   "Even though we have demonstrated a higher risk of NAION in persons with T2D exposed to once-weekly semaglutide, it is important to keep in mind that use of semaglutide comes with substantial advantages for patients as given by the improved glycemic control, reduction in risk of cardiovascular disease as well as the beneficial effects of weight loss [1]. As such, the observed incidence rate of NAION of 0·228 per 1000 person-years for persons with T2D exposed with once-weekly semaglutide may not discourage semaglutide treatment but needs to be acknowledged as a potential risk."
2. Also, interested in the mechanism of how the medication reduces perfusion to the nerve.
   "As the pathogenic pathway of NAION is insufficiently understood, it is difficult to speculate as to how semaglutide may lead to elevated risk. Expression of glucagon-like peptide-1 receptor agonist receptors have been identified in the optic nerve [20], but it is unknown whether continuous stimulation of these with specific glucagon-like peptide-1 receptor agonists may alter vascular perfusion of the optic nerve head. In SUSTAIN-6, use of once-weekly semaglutide led to an increased risk of diabetic retinopathy worsening (HR 1·76, 95% CI 1·11 − 2·76) [1], and it has been speculated that this can likely be attributed to early worsening given the rapid improvement in glycemic control in the semaglutide arm [21]. While persons exposed to semaglutide in our study also had impaired glycemic control (hemoglobin A1c 54 vs. 49 mmol/mol in non-exposed group), our findings of an increased risk of NAION were still statistically significant after adjustment for glycemic control, indicating a likely different mode of action as in diabetic retinopathy."

Hope this helps!

Gooday everyone!

Hi Dr NS,

Answers to your questions from the Danish study (Grauslund, J., Taha, A.A., Molander, L.D. et al. Once-weekly semaglutide doubles the five-year risk of nonarteritic anterior ischemic optic neuropathy in a Danish cohort of 424,152 persons with type 2 diabetes. Int J Retin Vitr 10, 97 (2024). )

The answers sound very logical, but nobody wants to knowingly lose vision, whatever the advantages of the drug are.

1. I am curious what the conversations are with your patients. Diabetics with disk at risk, should they avoid ever taking the medication?If a patient experiences NAION do you automatically advise to discontinue the medication?
   "Even though we have demonstrated a higher risk of NAION in persons with T2D exposed to once-weekly semaglutide, it is important to keep in mind that use of semaglutide comes with substantial advantages for patients as given by the improved glycemic control, reduction in risk of cardiovascular disease as well as the beneficial effects of weight loss [1]. As such, the observed incidence rate of NAION of 0·228 per 1000 person-years for persons with T2D exposed with once-weekly semaglutide may not discourage semaglutide treatment but needs to be acknowledged as a potential risk."
2. Also, interested in the mechanism of how the medication reduces perfusion to the nerve.
   "As the pathogenic pathway of NAION is insufficiently understood, it is difficult to speculate as to how semaglutide may lead to elevated risk. Expression of glucagon-like peptide-1 receptor agonist receptors have been identified in the optic nerve [20], but it is unknown whether continuous stimulation of these with specific glucagon-like peptide-1 receptor agonists may alter vascular perfusion of the optic nerve head. In SUSTAIN-6, use of once-weekly semaglutide led to an increased risk of diabetic retinopathy worsening (HR 1·76, 95% CI 1·11 − 2·76) [1], and it has been speculated that this can likely be attributed to early worsening given the rapid improvement in glycemic control in the semaglutide arm [21]. While persons exposed to semaglutide in our study also had impaired glycemic control (hemoglobin A1c 54 vs. 49 mmol/mol in non-exposed group), our findings of an increased risk of NAION were still statistically significant after adjustment for glycemic control, indicating a likely different mode of action as in diabetic retinopathy."

Hope this helps!

Gooday everyone!