March 12, 2024

Ozempic may delay kidney disease progression, latest trial results show

  • Type 2 diabetes is a condition that results from the body no longer responding to insulin, the hormone that controls blood glucose levels.
  • People with type 2 diabetes are at high risk of developing chronic kidney disease.
  • Semaglutide — sold under the brand name Ozempic — is a drug that, in conjunction with diet and exercise, improves blood glucose (sugar) control in people with diabetes.
  • Now, trial results show that semaglutide may also reduce the progression of kidney disease.

Chronic kidney disease affects one in three adults with diabetes. Both type 1 and type 2 diabetes increase the risk of chronic kidney disease if blood glucose (sugar) levels are not controlled.

The resulting damage to blood vessels and nephrons in the kidneys means they cannot function effectively.

As the early stages of kidney disease cause few or no symptoms, people with diabetes should manage their blood glucose, blood pressure and cholesterol levels. They should also get regular checks from their doctor.

Semaglutide, which is marketed as Ozempic, is one of a group of drugs called glucagon-like peptide-1 (GLP-1) receptor agonists. These mimic a hormone — GLP-1 — that makes the body produce more insulin, reduces appetite and gives feelings of fullness.

The Food and Drug Administration (FDA) has approved Ozempic as a treatment for type 2 diabetes, in addition to diet and exercise.

As well as helping control blood glucose, it may also reduce the risk of heart attack, stroke, or death in adults with type 2 diabetes and heart disease. One study has shown that it could also reduce inflammation, which may explain these other health effects.

Dr. Joshua J. Neumiller, PharmD, American Diabetes Association Board president-elect for healthcare and education, told Medical News Today that “[b]uilding evidence suggests that GLP-1 receptor agonists suppress inflammation and reduce oxidative stress and fibrosis in the kidney, together slowing [chronic kidney disease] progression.”

Now, the manufacturer of Ozempic — Novo Nordisk — has announced headline results of their latest trial, suggesting that semaglutide can reduce the risk of kidney disease progression by 24% in people who have type 2 diabetes and chronic kidney disease.

The detailed results of the FLOW trial will be presented at a scientific conference later this year. They have not yet appeared in a peer-reviewed journal.

Prof. Peter Rossing, research leader at the Steno Diabetes Center in Copenhagen, Denmark, one of the researchers involved in the trial, spoke to MNT about these findings.

He emphasized:

“This is a very significant finding; over 500 million people have diabetes, and 30-40% have chronic kidney disease, and we need treatments to stop or reduce progression of the kidney disease as well as to reduce the burden of cardiovascular disease which is high in this population.”

Prof. Rossing previously co-authored a paper explaining the rationale, design and baseline data of the FLOW trial.

Dr. Neumiller, who was not involved in this research agreed with this view, noting that “[t]hese headline results from FLOW are very important for people with [type 2 diabetes] and [chronic kidney disease] and the clinicians who care for them.“

“People with [type 2 diabetes] and [chronic kidney disease] are at amplified risk for cardiovascular-related morbidity and mortality and progression to kidney failure. Treatment options capable of mitigating heart and kidney risk in this population are greatly needed,” he told us.

Ozempic trial stopped early as it reached endpoint

Researchers on the FLOW trial recruited 3,533 people with type 2 diabetes and chronic kidney disease from 418 locations in 28 countries

They randomly allocated them to semaglutide or placebo. Participants self-administered both semaglutide and the visually identical placebo by weekly subcutaneous injection.

Those in the semaglutide group started on a dose of 0.25 milligrams (mg) per week for 4 weeks, increasing the dose to 0.5 mg, then to 1 mg after 8 weeks and for the rest of the trial.

In addition, all participants received the maximum labelled or tolerated dose of a RAAS blocking agent — unless contraindicated or not tolerated — which helps control hypertensionacute myocardial infarction (heart attack), chronic systolic heart failurestroke, and diabetic renal disease.

Participants had a mean age of 66.6 years, 69.7% were men and 65.7% were white. All participants had type 2 diabetes diagnosed, on average, 17.4 years before the start of the trial and chronic kidney disease.

The trial was meant to run until the end of 2024, but was stopped early after it reached its primary endpoint, which Prof. Rossing explained:

“The endpoint is composed of kidney disease progression and cardiovascular and kidney death, and in particular progression to kidney failure and mortality of cardiovascular events. These are frequent in this population of [type 2 diabetes] with [chronic kidney disease], so that we can reduce this with 24% is important and meaningful for patients.”

Ozempic could protect kidney health, reduce cardiac death risk

In the announcement, Novo Nordisk stated that the trial had achieved “a statistically significant and superior reduction in kidney disease progression as well as cardiovascular and kidney death of 24% for people treated with semaglutide 1.0 mg compared to placebo.”

However, Prof. Jagdish Khubchandani, professor of public health at the New Mexico State University, not involved in the trial, cautioned that these are, nevertheless, early-stage findings.

He advised that:

“There needs to be repeated assessment with different samples of participants across the world. In the real world setting, people behave differently and have other conditions as well. So, we need more effectiveness trials — [because] effectiveness trials find how well a medication works [unlike] efficacy trials that measure how well it works in RCT/lab studies.”

Dr. Neumiller echoed this perspective.

“FLOW represents the first dedicated kidney outcome trial with a GLP-1 receptor agonist in people with [type 2 diabetes] and [chronic kidney disease],“ he told us.

“The recently released headline results are impressive, yet we await presentation and publication of the complete trial results to fully understand the efficacy and safety outcomes of the trial,” Dr. Neumiller cautioned.

Ozempic is not without side effects

Although Ozempic is effective in regulating blood glucose and, according to this announcement, could reduce the risk of complications of chronic kidney disease, it does have side effects, which people taking the drug should be aware of.

Many people taking the drug report the following mild side effects:

  • gas and burping
  • nausea, vomiting and diarrhea
  • abdominal pain
  • constipation
  • fatigue
  • changes in the sense of taste.

More serious, but rare, side effects may include:


Can Ozempic change the treatment landscape?

Dr. Ishita Prakash Patel, M.D., board-certified endocrinologist at Texas Diabetes and Endocrinology, not involved in this study, also commented on its findings for MNT.

She expressed some optimism, noting that:

“If the claims are sturdy, this class of medication would be another validated tool in our kit to not only treat blood sugars and weight, but one of the more devastating outcomes of uncontrolled diabetes – chronic kidney disease. This is good news for people with [type 2 diabetes].”

Other experts agreed that this could be an important step forward in the search for effective treatments for chronic kidney disease in people with type 2 diabetes.

Dr. Neumiller told us: “Results from FLOW will, in my opinion, have a dramatic impact on the standard of care for people living with [type 2 diabetes] and [chronic kidney disease]. With primary evidence of kidney benefit in the setting of [type 2 diabetes] and [chronic kidney disease], we now have an agent capable of mitigating heart and kidney risk with a robust and preserved glucose-lowering effect at low eGFR.”

Prof. Khubchandani agreed, saying: “Given that these medications have multiple beneficial effects, help control blood sugar, and are reasonably well tolerated with kidney dysfunction, these could change the landscape of treatment for those with [type 2 diabetes] and kidney dysfunction which is common among people with [type 2 diabetes].”

https://www.medicalnewstoday.com/articles/ozempic-may-delay-kidney-disease-progression-latest-trial-results-show#Can-Ozempic-change-the-treatment-landscape?

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