GLP-1 raises Ozempic retinopathy… Reconfirmed in large-scale analysis

The side effect issue of diabetic retinopathy (DR) of type 2 diabetes treatment glucagon-like peptide-1 receptor agonist (GLP-1 RA) has been reconfirmed.

At the time of the development of semaglutide, an increase in retinopathy patients was observed in clinical trials, but as a similar trend was found in a meta-analysis involving a total of 60,000 patients, monitoring for high-risk groups is expected.

The results of a study on the relationship between GLP-1 medication administration and retinopathy, conducted by Stuart G. Albert of the Department of Endocrinology at St. Louis Medical School, USA, were published in the January issue of Diabetes and Metabolic Syndrome: Clinical Studies and Reviews (doi.org/10.1016/j. dsx.2022.102696).

GLP-1 is a drug that reduces major cardiovascular side effects in patients with type 2 diabetes and cardiovascular disease (CVD), and has recently expanded its use to obesity treatment.

Injectable semaglutide (product name: Ozempic)

The problem is that an abnormal increase in diabetic retinopathy was observed during the course of the SUSTAIN clinical trial of the drug semaglutide.

As related information was reported at the American Diabetes Association in 2017, interpretations among experts were divided over the cause. The most convincing hypothesis is that a sharp drop in glycated hemoglobin (A1c) aggravated the symptoms.

The researchers undertook a meta-analysis to comprehensively analyze multiple studies to determine whether the worsening of diabetic retinopathy was affected by a reduction in drug type or A1c.

Regression analysis was performed on 7 studies (n = 56 004) and 11 studies (n = 11 894 participants) on semaglutide that looked at the main cardiovascular outcome trial (CVOT) of GLP-1 RA. did.

As a result of the analysis, overall, GLP-1 preparations did not significantly increase the relative rate (RR) of retinopathy (RR 1.09), but it was confirmed that the decrease in A1c and the duration of administration correlated with the increase in diabetic retinopathy. .

In a sub-analysis of 11 studies on semaglutide, differences were observed depending on the formulation.

Six studies (n = 5610) administered oral semaglutide and five studies (n = 6284) administered subcutaneous semaglutide, and overall the relative incidence of new and worsening retinopathy was increased ( RR 1.22).

In particular, for diabetic retinopathy, when subcutaneous semaglutide was administered for more than one year, the relative rate (RR) increased by 56%, and when A1c decreased by more than 1.0%, it increased by 59%. These two items are the main risks Confirmed that it is a factor.

“This meta-analysis shows that rapid improvement in A1c is correlated with an increase in retinopathy rates as well as improved cardiovascular events,” said the researchers. It can help,” he said.

“Unlike the increased risk of subcutaneous semaglutide, there was no such difference with oral administration,” he said. “Therefore, close cooperation with ophthalmologists to assess the risk of retinopathy according to the high-risk group and dosage form after starting GLP-1 medication. It has to be done,” he added.

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