These Medications Might Make Diabetic Retinopathy Worse

Diabetic retinopathy is a common complication of diabetes that affects the blood vessels in the retina, the light-sensitive tissue at the back of the eye. If left untreated, diabetic retinopathy can cause severe vision loss or even complete blindness.

The good news is that diabetic retinopathy (DR) can be diagnosed long before it actually begins to impact your vision. The condition is very treatable, and potentially even reversible, especially when caught early.

Doctors have a good understanding of what causes DR: high blood sugar, high blood pressure, and, to a lesser extent, high cholesterol. Diabetic retinopathy is very sensitive to metabolic health, and many of the medications that people with diabetes commonly take can affect its progression and development — for better or for worse.

This article will review the drugs that we know (or suspect) might worsen diabetic retinopathy.

Warning

A quick word of warning: this article shouldn’t be taken as medical advice, and no patient is qualified to decide for themselves whether or not to avoid any drug listed here. Many of these medications are important for the health of millions of adults, and their benefits may easily outweigh whatever effect they might have on DR.

If you’re concerned that you may be taking a medication that could make your diabetic retinopathy worse, please talk to your doctor. Only a medical professional is qualified to assess the unique totality of your health conditions to recommend medication adjustments.

The Two Diabetes Drugs that (Might) Make DR Worse

Most diabetes drugs have beneficial effects for diabetic retinopathy, slowing its progression and potentially even helping to reverse the damage. Taking your glucose-lowering medications as prescribed by your doctor is absolutely one of the best ways to protect yourself from DR.

There are, however, one and possibly two exceptions to that rule, as described by a recent survey of the topic in the medical journal Eye.

Thiazolidinediones (TZDs)

TZDs have been called “the forgotten diabetes medication.” These pills directly improve insulin resistance, a root cause of type 2 diabetes, but have been de-emphasized by authorities due to concerns over harmful side effects, including cardiovascular disease.

Although these drugs are increasingly out of fashion, they are still commonly prescribed. As of 2019, about 8 percent of people with type 2 diabetes used a TZD.

TZD’s carry a known risk of diabetic macular edema (DME), an especially damaging form of diabetic retinopathy that affects our keenest vision in the center of our eyesight. TZDs can cause fluid retention, which appears to exacerbate the swelling of blood vessels that characterizes DME. It only happens in a small number of cases — fewer than 3 percent of those that use the drug.

There are now two types of TZDs on the market:

rosiglitazone (Avandia)
pioglitazone (ACTOS)

Luckily, cessation is associated with rapid eye improvement.

Ozempic

There is some evidence that semaglutide (Ozempic), a GLP1-RA, may increase the incidence of diabetic retinopathy. One of several pivotal studies of semaglutide found an increased risk of DR, and the FDA has reported that a significantly higher percentage of Ozempic users have DR in comparison with users of similar drugs like dulaglutide (Trulicity) and liraglutide (Victoza). The connection is disputed, however, as another large study of semaglutide found no such risk.

Even if the association is real, it’s very possible that your own doctor would conclude that semaglutide is worth the risk. Ozempic is a very effective drug for people with diabetes, typically conferring both rapid glycemic improvements and weight loss.

It seems possible that Ozempic’s effectiveness, in fact, explains its negative effect on the eyes. Contrary to all expectations, rapid improvement in glucose control can actually worsen diabetic retinopathy. This is called “early worsening,” because the eyes will get worse before the major long-term benefits of better blood sugar control become evident.

Experts don’t believe that this is necessarily a reason to avoid Ozempic. A recent discussion of the issue by experts from the American Academy of Ophthalmology suggested that “early worsening” from Ozempic is both “temporary and manageable,” although it does call for increased scrutiny from eye doctors.

Other Drugs with Negative Metabolic Effects

Drugs that Increase Blood Sugar

Some medications are known to cause blood sugar spikes, including:

Steroids, including hydrocortisone and prednisone, can have a dramatic effect on blood sugar. (Steroid creams and inhalers do not have the same effect).
Hormonal birth control, including the pill, the shot, the patch, and the IUD.
Beta-blockers, which are used to treat hypertension, irregular heartbeat, and anxiety.
Anti-psychotic drugs, which are used to treat schizophrenia and related mental illnesses.

If you take any of the above drugs, it might be wise to make sure your main diabetes healthcare provider is aware of it. They may or may not suggest an adjustment.

Statins are also associated with rising blood sugar levels — but even taking that factor into account, experts still recommend statins for most adults with diabetes because they reduce the risk of cardiovascular disease.

Finally, if you have advanced diabetic retinopathy that requires treatment, you may be given steroid injections. These drugs can have a powerful anti-inflammatory effect within the eyeball that directly improves DR symptoms, even if they exert a negative effect on insulin sensitivity.

Drugs that Increase Blood Pressure

Hypertension (high blood pressure) is the other big factor that speeds the development and progression of diabetic retinopathy. Accordingly, medications that are known to raise your blood pressure can be considered risk factors for DR.

An incomplete list of some common drugs that can increase blood pressure includes:

Pain relievers, including acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen (Motrin, Advil) and naproxen (Aleve).
Antidepressants, including fluoxetine (Prozac), monoamine oxidase inhibitors, and tricyclic antidepressants
Decongestants, including pseudoephedrine (Sudafed, Contac) and phenylephrine (Sudafed PE).
Hormonal birth control, including the pill, the shot, the patch, and the IUD.
Stimulants, such as methylphenidate (Ritalin).

Some supplements, including caffeine and ginseng, can have a similar effect. The Mayo Clinic has a full article on the topic.

Drugs that Increase (Bad) Cholesterol

Experts are very confident that high blood sugar and high blood pressure both lead to diabetic retinopathy. The evidence linking high cholesterol with DR is not quite as strong, although we do know that some cholesterol-lowering drugs (especially fibrates) significantly reduce the incidence of DR.

These are some of the most common drugs that believed to elevate “bad” cholesterol (LDL and/or triglycerides), which may or may not be risk factors for DR:

Steroids
Hormonal birth control, including the pill, the shot, the patch, and the IUD.
Retinoids (used to treat acne)
Beta-blockers, which are used to treat hypertension, irregular heartbeat, and anxiety.
Diuretics

Drugs that Increase Weight

It should be no surprise that weight gain, which is so highly related to the development and progression of type 2 diabetes, is associated with an increased risk of diabetic retinopathy. A 2021 study in Korea found that patients with recent diagnoses of type 2 diabetes that lost 10 percent of their body weight cut their risk of DR in half, whereas those that had 10 percent weight gain tripled their risk.

It’s therefore probably fair to consider any drugs that cause weight gain as potential risk factors for DR.

Some of the most common drugs associated with weight gain include:

Tricyclic antidepressants, including amitriptyline (Elavil), doxepin (Silenor), and nortriptyline (Pamelor).
Selective serotonin reuptake inhibitors (SSRIs), another type of antidepressant, including escitalopram (Lexapro), paroxetine (Paxil), sertraline (Zoloft).
Anti-psychotics, particularly olanzapine (Zyprexa).
Anti-seizure medications, including gabapentin (Gralise), pregabalin (Lyrica), and vigabatrin (Sabril).
Steroids
Beta-blockers
Antihistamines

The diabetes medications insulin and sulfonylureas are also associated with weight gain, which is why diabetes authorities have recently begun to prefer other options for glucose control.

Takeaways

Diabetic retinopathy is largely caused by poor metabolic health: high blood sugar, high blood pressure, and possibly high cholesterol. Many prescription medications have undesirable metabolic side effects, and can therefore be considered potential contributors to DR.

Furthermore, two types of diabetes drugs in particular are associated with worsening diabetic retinopathy: the family of thiazolidinediones (TZDs), which includes rosiglitazone (Avandia) and pioglitazone (ACTOS), and semaglutide (Ozempic). Your ophthalmologist should be aware that you are taking one of these drugs, but will not necessarily advise a change, even if you are at a high risk of vision loss from DR.

Many of the drugs discussed in this article are vital to the health of millions; therefore, it’s impossible to say whether or not readers should avoid them. As always, the guiding hand of a doctor that understands your unique health status is critical. It’s sometimes up to you to make sure that your various specialists are all on the same page. We encourage you to ensure that your main diabetes care provider and ophthalmologist are aware of every medicine you take.

This article has concentrated on the effects that various medications have on diabetic retinopathy. Medicine, of course, is only one factor of many — diet, exercise, glycemic control, and many other decisions play an immense role in the development and progression of diabetes complications.

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