Category: Diabetes

Researchers at Wilmer Eye Institute, Johns Hopkins Medicine say they have evidence that an experimental drug may prevent or slow vision loss in people with diabetes. The results are from a study that used mouse as well as human retinal organoids and eye cell lines. Eye conditions that cause vision loss are common complications of diabetes, affecting nearly 8 million Americans—a statistic likely to almost double by 2040, according to the National Institutes of Health.

The team focused on models of two common diabetic eye conditions: proliferative diabetic retinopathy and diabetic macular edema, both of which affect the retina, the light-sensing tissue at the back of the eye that also transmits vision signals to the brain. In proliferative diabetic retinopathy, new blood vessels overgrow on the retina’s surface, causing bleeding or retinal detachments and profound vision loss. In diabetic macular edema, blood vessels in the eye leak fluid, leading to swelling of the central retina, damaging the retinal cells responsible for central vision.

Results of the study, published May 25 in the Journal of Clinical Investigation, show that a compound called 32-134D, previously shown to slow liver tumor growth in mice, prevented diabetic retinal vascular disease by decreasing levels of a protein called HIF, or hypoxia-inducible factor. Doses of 32-134D also appeared to be safer than another treatment that also targets HIF and is under investigation to treat diabetic eye disease.

Current treatment for both proliferative diabetic retinopathy and diabetic macular edema includes eye injections with anti-vascular endothelial growth factor (anti-VEGF) therapies. Anti-VEGF therapies can halt the growth and leakiness of blood vessels in the retina in patients with diabetes. However, these treatments aren’t effective for many patients, and may cause side effects with prolonged use, such as increased internal eye pressure or eye tissue damage.

Akrit Sodhi, M.D., Ph.D., an author of the new study, says that in general, the idea of inhibiting HIF, a fundamental protein in the body, has raised concerns about toxicity to many tissues and organs. But when his team screened a library of HIF inhibitor drugs and conducted extensive testing, “We came to find that the drug examined in this study, 32-134D, was remarkably well tolerated in the eyes and effectively reduced HIF levels in diseased eyes,” says Sodhi, associate professor of ophthalmology and the Branna and Irving Sisenwein professor of ophthalmology at the Johns Hopkins University School of Medicine and the Wilmer Eye Institute.

HIF, a type of protein known as a transcription factor, has the ability to switch certain genes, including vascular endothelial growth factor (VEGF), on or off throughout the body. In the eye, elevated levels of HIF cause genes like VEGF to increase blood vessel production and leakiness in the retina, contributing to vision loss.

To test 32-134D, researchers dosed multiple types of human retinal cell lines associated with the expression of proteins that promote blood vessel production and leakiness. When they measured genes regulated by HIF in cells treated with 32-134D, they found that their expression had returned to near-normal levels, which is enough to halt new blood vessel creation and maintain blood vessels’ structural integrity.

Researchers also tested 32-134D in two different adult mouse models of diabetic eye disease. In both models, injections were administered into the eye. Five days post-injection, the researchers observed diminished levels of HIF, and also saw that the drug effectively inhibited the creation of new blood vessels or blocked vessel leakage, therefore slowing progression of the animals’ eye disease. Sodhi and his team said they also were surprised to find that 32-134D lasted in the retina at active levels for about 12 days following a single injection without causing retinal cell death or tissue wasting.

“This paper highlights how inhibiting HIF with 32-134D is not just a potentially effective therapeutic approach, but a safe one, too,” says Sodhi. “People facing diabetic eye disease and vision loss include our family members, friends, co-workers—this is a disease that impacts a large group of people. Having safer therapies is critical for this growing population of patients.”

Sodhi says that further studies in animal models are needed before moving to clinical trials.

GLP1 receptor agonists — a class of diabetes medications — are associated with fewer major adverse cardiovascular events than another type of diabetes drug (DPP4 inhibitors) in older veterans with no prior heart disease. The findings, reported May 9 in Annals of Internal Medicine, will aid clinicians in choosing a diabetes drug regimen for older patients.

“We believe this study is an important contribution to patient care and adds to what we as clinicians know about treating diabetes and heart disease prevention,” said Christianne Roumie, MD, MPH, professor of Medicine in the Division of General Internal Medicine and Public Health and senior author of the study.

More than 30 million adults in the United States have diabetes mellitus, and this diagnosis increases risk for adverse cardiovascular events (heart attack, stroke or cardiovascular death) and heart failure hospitalization, noted Lee Richardson, MD, a fellow in the Division of Cardiovascular Medicine and first author of the new study.

The researchers sought to address two knowledge gaps, Richardson said: first, that many newer diabetes medications were tested versus a placebo, making it difficult to know if one type offers an advantage over another, and second, that the clinical trials showing cardiovascular benefits for these drugs were conducted in people who already had heart disease.

“We wanted to see if there were differences in MACE — major adverse cardiovascular events — when comparing two commonly used drug classes, GLP1 receptor agonists and SGLT2 inhibitors, versus an active comparator, DPP4 inhibitors, in people without heart disease,” Richardson said.

DPP4 inhibitors are regarded as neutral with respect to cardiovascular events and continue to be widely used, he added.

In a retrospective cohort study of U.S. veterans, the researchers found addition of a GLP1 receptor agonist was associated with about a 20% reduced risk of MACE and heart failure hospitalization, compared to treatment with a DPP4 inhibitor in patients with Type 2 diabetes and no prior heart disease. The reduced risk translates to about three fewer heart failure, death, heart attack or stroke events in 1,000 people using the medication for a year, Roumie said.

SGLT2 inhibitors did not reduce MACE and heart failure hospitalization compared to DPP4 inhibitors for primary heart disease prevention.

The study included nearly 100,000 veterans who received a first prescription for an antidiabetic medication (metformin, insulin or sulfonylurea) from 2001 to 2016, and then added a GLP1 receptor agonist, SGLT2 inhibitor or DPP4 inhibitor to their diabetes treatment regimen. Follow-up data was collected through 2019.

The median patient age was 67 years, and the median diabetes duration was 8.5 years. The researchers included variables such as age, sex, race, body mass index, blood pressure, laboratory values like hemoglobin A1c, and history of prior illnesses in the statistical analysis.

The study did not examine the use of GLP1 receptor agonists, SGLT2 inhibitors or DPP4 inhibitors as first-line therapies for Type 2 diabetes treatment.

“Diabetes and its complications represent an enormous health care burden and result in nearly 200,000 deaths annually, often due to heart disease,” Roumie said. “Doctors, scientists and patients want to do our best to prevent heart disease for those who are at highest risk. We believe that future primary prevention trials with these antidiabetic medications are needed. For some patients, these medications cost a lot, but if they prevent heart disease, then there would be a great return on investment.”

Richardson noted that a limitation of the current study is that most of the patients were white men.

“The hope for future primary prevention trials is that they would enroll a diverse cohort of participants who represent the patients we see in our clinics on a day-to-day basis,” he said.

GLP1 receptor agonists include the medications exenatide, liraglutide, semaglutide and others; SGLT2 inhibitors include empagliflozin, dapagliflozin and canagliflozin; DPP4 inhibitors include alogliptin, linagliptin, saxagliptin and sitagliptin.

Study authors also included Alese Halvorson, MS, Amber Hackstadt, PhD, Adriana Hung, MD, MPH, Robert Greevy, PhD, Carlos Grijalva, MD, MPH, and Tom Elasy, MD, MPH. The research was supported by a VA Clinical Science Research and Development investigator-initiated grant and in part by the Center for Diabetes Translation Research supported by the National Institutes of Health (grant DK092986).

This document is a summary of the European Public Assessment Report (EPAR) for Ozempic.
It explains how the Agency’s evaluation of the medicinal product led it to recommend its authorisation in the EU and its conditions of use.
recommended its authorisation in the EU and its conditions of use. It is not intended to
provide practical advice on how to use Ozempic.
For practical information on the use of Ozempic, patients should read the package insert or contact their doctor or pharmacist.
or contact their doctor or pharmacist.

What is Ozempic and what is it used for?
Ozempic is a diabetes medicine used in addition to diet and exercise to treat adults with
to treat adults with uncontrolled type 2 diabetes.
is not adequately controlled.
Ozempic can be used alone in patients who cannot take metformin (another diabetes medication).
diabetes medication). It can also be used as an “add-on” to other diabetes medicines.
diabetes medicines.
Ozempic contains the active ingredient semaglutide.
How is Ozempic used?
Ozempic is available as an injectable solution in pre-filled pens and is only available on
prescription only. It is injected under the skin of the stomach, thigh or upper arm.
The initial dose of Ozempic is 0.25 mg once a week. After four weeks, the dose should be increased to
increased to 0.5 mg. If necessary, the dose can be further increased to a maximum of 1 mg,
once a week. For more information, see the package insert.

How does Ozempic work?
The active ingredient in Ozempic, semaglutide, is a “GLP-1 receptor agonist”. It works in the same way as
the same way as GLP-1 (a hormone produced in the gut), by increasing the amount of insulin
released by the pancreas after food intake. This action helps to control blood
glucose levels in the blood.

What benefits has Ozempic shown in studies?
Studies have shown that Ozempic is effective in lowering blood glucose levels and reducing
health complications in patients with type 2 diabetes.
Five studies involving more than 4,000 patients showed that Ozempic reduced HbA1c
(a measure of glucose in the blood) within a range of 1.2 to 1.8 percentage points
over a period of 10 to 13 months. In these studies, compared to other treatments, namely
sitagliptin, exenatide and insulin glargine (which resulted in reductions of 0.55, 0.92, 0.83 percentage points
percentage points respectively) and placebo (reductions of up to 0.09 percentage points),
Ozempic performed better. In addition, the results showed that treatment with Ozempic
was associated with a beneficial reduction in body weight.
Another study in more than 3,000 patients with diabetes and a high risk of heart problems showed that, with Ozempic
heart problems showed that, in general, a heart attack, stroke or death was not associated with
death occurred less frequently in patients treated with Ozempic
(6.6%) compared to placebo patients (8.9%). When looking at the three “events” separately, fewer patients on Ozempic
events” separately, fewer Ozempic patients had a heart attack or stroke, but death rates were
stroke, but the rates of death due to heart problems were similar in both groups.
both groups.

What are the risks associated with using Ozempic?
The most common side effects seen with Ozempic (which may affect more than 1 in 10 people) include
more than 1 in 10 people) include digestive system disorders such as diarrhea, vomiting and nausea (which can be
vomiting and nausea (sickness). They are mild to moderate in intensity and short in duration.
duration. Serious worsening of diabetic retinopathy (damage to the retina, the light-sensitive membrane at the back of the eye)
serious worsening of diabetic retinopathy (damage to the retina, the light-sensitive membrane at the back of the eye) is common (up to one in 10 people).
For a full description of the side effects and limitations of Ozempic, see the
package insert.

Why is Ozempic approved?
Ozempic has been shown to be effective in controlling blood glucose levels. Treatment with
Ozempic also resulted in weight loss, which is considered beneficial in
patients with diabetes. Ozempic has also been shown to be effective in reducing the occurrence of
complications of diabetes, such as heart attacks and strokes.
and stroke.
In terms of safety, this was considered to be consistent with other drugs in the same class.
drugs in the same class. Adverse events affecting the gastrointestinal system are considered
considered manageable. Worsening of diabetic retinopathy was also observed and will be further studied.
be further investigated.

The European Medicines Agency considered that the benefits of Ozempic observed in the studies outweighed the risks and recommended that Ozempic be used in a
studies outweighed the risks and recommended that Ozempic be approved for use in the EU.
be approved.

What steps are being taken to ensure the safe and effective use of Ozempic?
of Ozempic?
Recommendations and precautions for healthcare professionals and patients to ensure the safe and effective use of Ozempic
and patients to ensure the safe and effective use of Ozempic have been included in the summary of
product characteristics and in the package insert