Rapid Weight Loss a Diabetic Retinopathy Risk?

While rapid weight-loss with bariatric surgery or drugs might temporarily worsen diabetic retinopathy as blood sugar levels are rapidly corrected, the low overall risk likely doesn’t outweigh the benefits of weight loss, according to a review.

Altogether, the studies are conflicting and the evidence insufficient, Basil K. Williams Jr., MD, of the University of Miami, and colleagues concluded in Current Opinion in Ophthalmology.

For example, in a 1998 randomized study, diabetic retinopathy worsened at 6 months in 3.5% (25 of 711) of patients treated with intensive insulin therapy compared with 1.2% (nine of 728) of those on conventional insulin therapy (OR 2.98, P=0.006). At 4-year follow-up, though, retinopathy wasn’t worse than at baseline in either group.

But a 2020 multicenter case-control study of 3,145 patients with type 2 diabetes found no link between the use of GLP-1 agonists — a category that includes semaglutide (Ozempic, or Wegovy for weight loss) — and worsening diabetic retinopathy (P=0.47).

“The goals for diabetic retinopathy treatment are to get blood sugars, blood pressure, and weight under control. This is by far the most important thing to do for the long term, so whatever approach is right for the patient is going to be the ideal treatment,” Williams told MedPage Today. “However, it is really important to have a conversation with the patient upfront to let them know that this may worsen retinopathy temporarily. But in the long run, it’s going to be beneficial for them.”

According to the review, an estimated 9.6 million people in the U.S. have diabetic retinopathy, including about one-quarter of patients with diabetes mellitus.

Clinicians have long suspected that rapidly improving blood sugar can make eye health worse. Back in 1998, the insulin therapy study noted that “there have been many reports of the curious, unanticipated, and seemingly paradoxical worsening of diabetic retinopathy after rapid improvement of blood glucose control.”

For the new review, researchers wanted to better understand the effect of rapid weight loss and improvement of HbA1c in light of the new generation of GLP-1 agonists, Williams said.

Some research did show that “when you get the diabetes controlled very, very rapidly, you can get some transient worsening of the diabetic retinopathy that improves over time,” he said.

The mechanism appeared to be related to changes in osmotic pressure in the vessels in the vascular system, he said. As blood sugar control improves, “the pressure gradient between inside the vessels and outside the vessels is different. There are more proteins now outside the vessels, and that pulls more fluid outside the vessels. That causes a little bit of additional leakage.”

This change stabilizes over time, he said. The review suggested that a sudden 2% or greater drop in HbA1c could impact retinopathy progression for 6 to 12 months. “Then things would be improving from there,” Williams noted.

Moving forward, Williams predicted that the new generation of weight-loss drugs “will be really valuable and decrease the long-term implications of diabetic retinopathy on our population. But we do have to consider that there’s a small percentage of people who will have some transient worsening. Navigating those small negatives with the overall greater benefit is something we’re going to have to deal with more and more.”

For now, the review authors recommended that patients undergo a baseline retinal examination before intensive glycemic control that leads to a rapid decrease in weight, followed by continued monitoring.

The review authors examined studies into tight insulin control, bariatric surgery, and GLP-1 agonists. They highlighted a 2022 systematic review and meta-analysis that found that four major randomized controlled trials linked GLP-1 agonists to rapidly worsening diabetic retinopathy but also to cardiovascular benefits.

Also, a 2016 study of semaglutide linked the drug to a higher risk of retinopathy complications (HR 1.76, 95% CI 1.11-2.78, P=0.02), although the numbers of patients affected were small (3% [50 of 1,648] with semaglutide vs 1.8% [146 of 1,649] with placebo).

The review did not include a matched cohort study presented last year at the annual meeting of the American Society of Retina Specialists. Ehsan Rahimi, MD, of Stanford University in California, reported that treatment with GLP-1 agonists almost doubled the likelihood of progression from nonproliferative to proliferative diabetic retinopathy after 3 years (RR 1.585, 95% CI 1.337-1.881, P<0.0001). The drugs were also linked to significantly higher rates of progression to diabetic macular edema.

“We see these patients in our clinics all the time,” Rahimi said at the 2023 conference. “They go on these medicines, and their HbA1c crashes, goes down very quickly. That rapid reduction is thought to play some role. But if you look at the basic science literature, it’s suggested that there are direct effects of these medications on the retina. That being said, it’s also been suggested that there may be a protective effect on the retina. We’re getting a lot of mixed signals.”

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