diabetes medications

These Medications Might Make Diabetic Retinopathy Worse

Posted by

0


Ksenia Chernaya/Pexels

By Ross Wollen

December 19th, 2022

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 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 deemphasized 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.

TZDs 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 GLP-1RA, 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:

  • 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 are 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 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.

Diabetes Medications: Should You Deprescribe Them in the Elderly?

Posted by

0


Deprescribing Antihyperglycemics

Researchers at the deprescribing project based at the Bruyère Research Institute in Ottawa, Canada, have just published another deprescribing algorithm, this one focused on antihyperglycemic agents.[1] The aims is to guide healthcare professionals in stopping, switching, or lowering the dose of these drugs in patients at risk for hypoglycemia or other antihyperglycemic adverse effects or in whom the drug’s benefit is uncertain due to frailty, dementia, or limited life expectancy. Lead author Barbara Farrell, PharmD, spoke with Medscape about the guideline and its recommendations.

Recent studies in the United States and Canada have shown that many older patients with diabetes are still being treated to A1c <7%.

“The intensity of glycemic control needed in older people is quite controversial, with different diabetes guidelines recommending different targets,” explained Dr Farrell. Around 5 years ago, treatment guidelines, which had previously favored a glycated hemoglobin (A1c) target of <7% (53 mmol/mol) for most people, set less stringent targets for the elderly (age ≥65 years). Many current international and national guidelines now recommend approximate treatment goals of <7.5% (58 mmol/mol) in healthy older adults and <8.5% (69 mmol/mol) in the very frail elderly.[2,3,4,5,6] These changes in targets result from clinical trials showing that compared with conventional glycemic control, intensive control did not significantly reduce all-cause or cardiovascular mortality.[7] It did, however, increase the risk for hypoglycemia and serious adverse events,[8,9] especially in elderly patients.[10,11]Hypoglycemia is associated with cardiovascular events, cognitive impairment, fractures, death, and reduced quality of life.[12,13] It is a leading cause of emergency department visits in older adults in the United States.[14]Hospitalization for hypoglycemia is associated with a poor prognosis.[15]

Need for New Guidelines

Despite the new guidelines and “Choosing Wisely” campaigns specifically cautioning against intensive glycemic control in the elderly,[16,17] recent studies in the United States and Canada have shown that many older patients with diabetes are still being treated to A1c <7%.[18,19,20,21,22]

“In the United States and Canada, the concept of treating to specific number targets has been very entrenched in the medical communities and among the public, so it is a difficult thing to change,” Dr Farrell stressed. “The diabetes guidelines all talk about how to start these drugs, and some of them discuss how to adjust doses for kidney function or for age, but they don’t specifically address how to reduce a dose or how often to monitor while you are reducing it. That is why we developed the deprescribing guideline, to fill that gap,” Dr Farrell explained. “For patients with low blood sugar, in particular the frail elderly, we wanted to be able to provide guidance to prescribers about when it might be appropriate to start reducing doses or just stopping some of those medications that can contribute to low blood sugar. What we are most concerned about is ensuring that people are switched off those medications and either continue on their remaining medications or with safer ones substituted. We need to be looking at safety as an increasing priority over the potential long-term benefits of keeping blood sugar very low. It is challenging because every person is different in terms of identifying when the balance of risk of medication versus benefit changes.”

The guideline does not set specific glycemic targets, referring to Canadian Diabetes Association and other, similar guidelines that address the need for less stringent targets in the elderly.

Which Drugs to Stop?

“There was a particular worry about glyburide, the long-acting sulfonylurea that frequently causes hypoglycemia,” Dr Farrell said. This usually happens because glyburide was started when patients were younger, and they have been taking it for many years, she explained. Switching glyburide to short- or long-acting gliclazide may reduce but will not eliminate the risk for hypoglycemia. Options other than a sulfonylurea should be considered.

“The other medication that can cause hypoglycemia is insulin, so cut back on the doses if the blood sugar is too low,” Dr Farrell added. The highest risk is with neutral protamine Hagedorn (NPH) insulin, and the guideline advises switching NPH insulin or mixed insulin to insulin detemir or glargine to reduce nocturnal hypoglycemia.

The guideline also lists the antihyperglycemic medications with no or low risk for hypoglycemia (Table).

Table. Medications With Low or No Risk for Hypoglycemia

Drug Risk for Hypoglycemia
Alpha-glucosidase inhibitors No
Dipeptidyl peptidase-4 (DPP-4) inhibitors No
Glucagon-like peptide-1 (GLP-1) agonists No
Meglitinides (glinides) Yes (low risk)
Metformin No
Sodium-glucose linked transporter 2 (SGLT2) inhibitors No
Thiazolidinediones No
Data from Farrell B, et al.[1]

Tapering and Monitoring

“There is no evidence that one tapering approach is better than another,” Dr Farrell noted. “With antihyperglycemic drugs, the only adverse effect from stopping is a rise in blood sugar that needs to be monitored. So if we have a patient who has very low blood sugar and no real problems with high blood sugar, we would just stop the sulfonylurea. If it’s a low dose of insulin, we would stop that. In other cases, we might gradually reduce the dose, either because we think the patient would still benefit from having the drug even at a lower dose, or sometimes the patient is reluctant to just stop suddenly.”

Frequency of monitoring the effects of deprescribing these drugs is highly individualized, depending on the patient’s blood sugar levels and on the drugs that have been changed.

Frequency of monitoring the effects of deprescribing these drugs is highly individualized, depending on the patient’s blood sugar levels and on the drugs that have been changed, Dr Farrell added. Monitoring need not be done daily unless insulin is being deprescribed. “If we are stopping glyburide or switching from glyburide to gliclazide, we might check once a week for a couple of weeks. Typically after most antihyperglycemic drugs are stopped, changes in blood glucose will be seen within 1 or 2 weeks,” she said.

Other Causes of Hypoglycemia

Another unique aspect of the new guideline is the inclusion of different situations that can contribute to hypoglycemia, such as taking insulin and then not eating, taking other drugs that cause hyper- or hypoglycemia, or drug interactions with antihyperglycemic medication. “Sometimes we see that a patient has recently stopped a drug that causes hyperglycemia, but the dose of the diabetes drug has not been reduced,” she explained. “For example, someone who is taking high-dose prednisone for a short period of time might experience a steep rise in blood sugar, and the dose of insulin or other antihyperglycemic drug is increased to cope with that. Then the prednisone is stopped, and the patient’s blood sugar plummets. We might simply avoid the particular drug that causes that drug interaction, or we would probably consider lowering the dose of the antihyperglycemic drug.”

Discussion With Patients and Families

One of the goals of the guideline is to encourage healthcare providers to discuss the rationale and benefits of deprescribing with patients and their families. “One of the biggest challenges is to explain the targets and the need to focus on safety versus not always focusing on preventing the long-term problems of diabetes,” Dr Farrell said. “This can be especially difficult with older people who may have had diabetes for 30 years, and it may seem as though suddenly, out of the blue, we’re not concerned about their blood sugar any longer. It is not an easy conversation to have, and it can be time-consuming,” she acknowledged.

“When these medications are first prescribed to a newly diagnosed person, and targets are discussed, it would be helpful to also explain that when they are older or if they start having hypoglycemic episodes, these targets may change,” she suggested. “We would establish that very intensive control is important in a younger person to prevent long-term complications but that as they get older we will revisit these targets, so they would know that modifying their targets as they get older is a normal part of the program.”

Updating the Guidelines

Dr Farrell pointed out that the systematic review of evidence done for preparation of the new guideline[23] identified only two relevant studies of deprescribing antihyperglycemic agents.[24,25] Both studies concluded that the approach is safe and feasible, but the quality of the evidence was low, the guideline authors commented. “We would benefit from having more studies of deprescribing so that we can get a better understanding about whether there is an optimal approach to tapering, monitoring, and follow-up,” Dr Farrell said. “Our eventual goal is that all prescribing guidelines will include deprescribing sections, so that specialists, family physicians, and all other healthcare professionals are on board with the approach.”

Biologics, Diabetes Meds Top 2016 Spending: Express Scripts

Posted by

0


Biologic anti-inflammatory drugs, diabetes medications, and cancer therapies were the top three categories of pharmaceutical spending in 2016 by employers who used the pharmaceutical benefit management (PBM) company Express Scripts.

One of every five dollars spent on prescription drugs was for a medication to treat an inflammatory condition or diabetes, according to the PBM’s2016 Drug Trend Report. St. Louis-based Express Scripts is the nation’s largest PBM, serving some 85 million Americans.

The company said it kept drug costs down for its clients through its various programs, though prices still increased. Average list prices for the most commonly used brand-name drugs increased 10.7% in 2016. Specialty drug costs continued to rise — 6.2% in 2016. Prices for the most commonly used generic drugs declined by 8.7%.

Certain individual drug categories continued to hit purchasers hard. Express Scripts’ employer clients paid almost $3,600 on average per prescription for an anti-inflammatory condition such as psoriasis or rheumatoid arthritis. Two brand names —Humira (adalimumab, AbbVie) and Enbrel(etanercept, Amgen) — were the biggest cost drivers in the class, with unit cost increases of 10% to 18%. The two therapies accounted for 70% of the anti-inflammatory market, despite there being 13 other available therapies, according to the PBM.

Spending on diabetes medications increased 19.4%, largely fueled by a 14% increase in unit cost. Express Scripts said that spending on insulins — which accounted for 40% of all diabetes spending — increased 10% from 2015 to 2016. Clients of the PBM paid $36.69 per insulin prescription, which was $1.63 more than 2015.

Oncology drug spending rose 22% in 2016, in part because unit costs for oral therapies increased by almost 10%. Express Scripts noted that oral chemotherapies are not subject to rebates or discounts “to any significant extent,” and that, since 2011, list prices for those medications have doubled from $20 per unit to $40 per unit.

Pain medications were the fifth costliest class of drugs for employers (after multiple sclerosis medications), with one in five of the PBM’s enrolees filling a prescription in 2016. Ninety-five percent of the prescriptions were for a generic. Even so, two brand-name medications helped drive costs up — Lyrica (pregabalin) and OxyContin(oxycodone).

Express Scripts also reported an uptick in spending on contraceptives and depression medications, bringing those two classes into the top 15 for drug spending for the first time. The Affordable Care Act (ACA) requires private plans on the exchanges and Medicaid programs to provide contraceptives free of charge. Insurance plans created after 2012 had the same requirement.

The ACA also required coverage of mental health services for exchange plans, Medicaid, and so-called nongrandfathered employer-based health plans.

Express Scripts reported a 34% decrease in spending on hepatitis C medications, which it said was due to decreased unit costs and less use. The two most-used therapies were Viekira Pak(ombitasvir/paritaprevir/ritonavir with dasabuvir) and Harvoni (ledipasvir/sofosbuvir), which accounted for just over 40% of the market.

The PBM said it expects hepatitis C spending to decline almost 29% each of the next 2 years, in part because it is negotiating better pricing forHarvoni. It is including both Viekira Pak/XR andHarvoni as preferred products on its formulary in 2017.

High traffic pollution may increase inflammation for insulin users

Posted by

0


Exposure to heavy traffic pollution may lead to an increase in C-reactive protein for those living with type 2 diabetes and using insulin, according to research in Environmental Pollution.

In contrast, adults assigned oral diabetes medications did not experience increases in C-reactive protein (CRP), a marker for inflammation, while exposed to the same amount of heavy traffic, according to researchers.

“According to our findings, [oral diabetes medication] users may be protected over time compared to insulin users,” the researchers wrote. “CRP concentration progressed in those on insulin but remained steady in those on [oral diabetes medications], in relation to proximity or number of major roadways.”

Christine Rioux, PhD, MS, assistant professor in the department of public health and community medicine at Tufts University School of Medicine in Boston, and colleagues analyzed data from 356 Puerto Rican adults (aged 44 to 75 years) with type 2 diabetes living in the Boston area. Within that group, 26% used insulin, 55% used oral diabetes medications and 19% reported using no diabetes medications.

Christine Rioux

Christine Rioux

Researchers assessed major road proximity and traffic density for each participant’s residential address. Approximately 20% of the group lived within 100 meters of one or more roads with more than 20,000 vehicles per day, and another 20% lived within 100 to 200 meters of roads with the same amount of traffic. Approximately 70% of the participants resided in the greater Boston area. Traffic considerations did not affect the selection criteria for the study.

Researchers measured CRP at the beginning of the study and again 2 years later.

Participants living within 100 meters of a busy roadway showed a 58.2% greater increase in CRP concentration (P =.054) compared with those living more than 200 meters away. Participants living between 100 and 200 meters of a busy roadway showed an 81% greater increase in CRP concentration (P = .03) compared with those living farther from busy roadways. Living near two or more busy roadways was associated with a 190% greater increase in CRP concentration (P = .001) compared with zero roadways.

Participants using oral diabetes medications and living near the highest traffic density showed a 49.3% relative decline in CRP concentration (P = .04).

The study is the first to examine the role that various type 2 diabetes medications may play when combined with a patient’s exposure to traffic pollution, according to researchers. The study builds on the research team’s previous work that suggested oral diabetes medications may provide a protective effect against inflammation for adults with type 2 diabetes.

“People on insulin appear to be even more susceptible to increases in inflammation when living in high traffic area,” Rioux said in a press release. “People can reduce their exposure to traffic pollution by keeping windows closed during the heaviest traffic periods of the day, using air conditioners in the summer months, and avoiding heavy exercise near busy roads, especially during peak traffic times.”

“We would like to examine the relationship between traffic pollution exposure, inflammation and type of diabetes medication in larger cohorts in other parts of the U.S. and world,” Rioux told Endocrine Today.  – by Regina Schaffer