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Ozempic Slows Kidney Disease, Cuts Cardiorenal Death Risk in Type 2 Diabetes, FLOW Study Finds

15 Minute Read
Close-up of Ozempic packaging

Ozempic (semaglutide), a medication originally developed to treat type 2 diabetes, is now demonstrating it confers other therapeutic benefits.

Key takeaways

  • People with type 2 diabetes and chronic kidney disease who took Ozempic (semaglutide) slowed the progression of kidney disease by 24% and cut their risk of death from kidney disease and major cardiac events, according to results of the FLOW trial published in the New England Journal of Medicine (NEJM).
  • Patients who took Ozempic versus placebo also cut their risk of major heart problems by 18%.
  • The FLOW trial’s results provide further evidence that GLP-1 class medications have benefits beyond diabetes and weight management, including chronic kidney disease, heart disease, and possibly liver disease.

People with type 2 diabetes and chronic kidney disease who took Ozempic (semaglutide) slowed the progression of their kidney disease and cut their risk of death from kidney disease and major cardiac events by 24% compared to participants who took a placebo, according to data from Novo Nordisk's FLOW trial published in the New England Journal of Medicine.

The trial’s results were published in conjunction with a presentation at the European Renal Association meeting in Stockholm. When added to standard care for diabetes and chronic kidney disease (CKD), Ozempic reduced the likelihood of having a major kidney disease event such as losing more than half of their kidney function, requiring dialysis, or needing a kidney transplant by 24%.

The study also showed that people who received Ozempic experienced slower rates of decline in kidney function, were 20% less likely to die from any cause, and were also 18% less likely to experience major adverse cardiac events (MACE). MACE includes non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death.

Anticipation of the FLOW trial’s results has run high ever since the Danish drugmaker announced that the trial had been halted early based on an interim analysis that the results were positive.

FLOW kidney outcomes trial: Study design

The FLOW trial was a phase 3 trial of more than 3,500 participants with type 2 diabetes and moderate to severe CKD in 28 countries. The study, which began in 2019, randomly assigned participants either a 1 mg dose of Ozempic (injectable semaglutide) or a placebo as an add-on to the standard treatment for CKD. 

The objective of the FLOW trial was to see if Ozempic delayed CKD progression and lowered risk of kidney- and cardiovascular-related death.

When and why did Novo Nordisk end the FLOW trial?

The FLOW trial was cut short in October of last year, one year ahead of schedule, after an interim analysis determined that the initial results were sufficient enough to prove the treatment was effective. Novo Nordisk, the Danish drugmaker behind Ozempic, said it plans to file for a label expansion of Ozempic in the U.S. and in the European Union in 2024.

What were the key findings? Did the FLOW trial meet expectations?

Ozempic slowed the progression of kidney disease and reduced the risk of death from kidney disease and major cardiac events by 24%. Full results of the trial were presented at the European Renal Association meeting in Stockholm and published in the NEJM. 

When the FLOW trial was halted, some industry experts were anticipating that results would demonstrate cardiorenal risk reduction of more than 30%, meaning that the trial fell short of some expectations.

In the trial, Ozempic was generally safe and well tolerated with side effects in line with other trials of the drug.

Novo Nordisk Headquarters
One of Novo Nordisk's U.S. research centers.

Were there any limitations of the FLOW study?

One limitation of the trial included the fact that roughly two-thirds of participants were white and approximately two-thirds were male. Although CKD affects one in three – a disproportionate amount – of Black people in America, Black participants accounted for just 4.5% of the trial population.

What happens now that the FLOW trial is over? 

Given the success of the FLOW trial, Novo Nordisk has said that it expects to file for a label expansion for Ozempic to include the prevention of kidney disease progression in patients with type 2 diabetes and CKD in the U.S. and European Union sometime this year.

What implications does the FLOW trial have for Ozempic and other drugs in its class?

There are a few implications that the results of this trial could have for Ozempic as well as other GLP-1 receptor agonists and incretin drugs in general.

Ozempic and other GLP-1s will likely also become treatment for kidney disease

These positive study results will likely set the stage for Ozempic – and other drugs in the same class, from oral semaglutide to injectable tirzepatide – to become a treatment option for kidney disease in addition to type 2 diabetes and obesity.

“The positive results from FLOW demonstrate the potential for semaglutide to become the first GLP-1 treatment option for people living with type 2 diabetes and chronic kidney disease,” Martin Holst Lange, Novo’s head of development, said.

In addition to Novo Nordisk’s planned label expansion for Ozempic, Eli Lilly is also enrolling patients in its own trial, TREASURE-CKD, to see if tirzepatide (marketed under the names Mounjaro and Zepbound) can treat CKD in people with obesity, both with and without type 2 diabetes.

Successful treatment of CKD with these medications could have implications that are far ranging. Lange estimated that 40% of people who live with type 2 diabetes also live with CKD. Given that an estimated 462 million individuals worldwide are affected by type 2, this means that nearly 185 million people could potentially stand to benefit from medications that improve kidney outcomes.

Ozempic and other GLP-1s will likely be compared to another diabetes drug class, SGLT-2 inhibitors

Given Ozempic’s reduction of kidney disease events in the FLOW study, it seems likely that the GLP-1’s will be used together with and compared against SGLT-2 inhibitor drugs. 

SGLT-2 inhibitors, which include Jardiance (empagliflozin) and Farxiga (dapagliflozin), are a different class of diabetes medications that have demonstrated kidney risk reduction. SGLT-2 inhibitors are widely used to guard against progression of kidney disease in adults with CKD, both with and without type 2 diabetes.

From a kidney disease event reduction standpoint, SGLT-2s will be tough competitors for Ozempic and other GLP-1s to beat. In comparable trials, SGLT-2 medications all demonstrated a greater reduction in kidney events than Ozempic did in the FLOW trial.

In one landmark trial, EMPA-KIDNEY, participants who took Jardiance had a 28% lower risk of progression of kidney disease or death from cardiovascular causes compared to those who didn’t. Another trial, DAPA-CKD, demonstrated a 39% risk reduction with Farxiga. And in the CREDENCE trial, patients with type 2 diabetes and CKD who took canagliflozin (Invokana) reduced their risk of kidney failure and cardiovascular events by 30%.

Could Ozempic and other diabetes drugs reduce the need for dialysis?

Dialysis Treatment
Patients receiving dialysis treatments.

Last October, the FLOW study proved so effective for CKD that it was cut short one year ahead of schedule, sending stocks of top dialysis providers such as DaVita and Fresenius Medical Care tumbling as shareholders considered the impact Ozempic and other GLP-1 medications might have on the treatment of kidney disease.

Currently the standard treatment for kidney failure has been kidney transplant as well as dialysis. It’s possible, however, that FLOW and other trials of diabetes drugs on kidney outcomes could potentially reduce the need for dialysis or transplant in some patients with CKD. Other studies have shown that the SGLT-2 inhibitor drug class slows the progression of kidney disease.

DaVita, one of the largest dialysis providers in the country, has been following such research closely. It has cast doubt on just how far-reaching Ozempic’s therapeutic benefits may be.

“It is nearly impossible to draw any conclusions from the FLOW study at this point,”Dr. Jeff Giullian, chief medical officer for DaVita, said at the time, adding, “Based on the inclusion criteria for study participants, we believe there may be limited application of the FLOW study findings to the overall CKD patient population.”

DaVita Dialysis Center
Signage for DaVita, one of the largest dialysis providers in the country.

He argued that the inclusion requirements necessary to partake in the FLOW trial, such as needing to be on a standard kidney disease treatment and have a certain amount of protein in the urine, were attributable to a narrow subset – less than 10% – of all current CKD patients.

“Future trials and research will be required to determine whether any findings derived from the FLOW study could benefit a CKD population beyond those studied in the trial,” Giullian said.

Ozempic is paving the way for ther GLP-1 drugs to treat conditions beyond kidney disease

The FLOW trial results, along with the recent announcement that Wegovy is approved to reduce cardiovascular risk in people with obesity, are the latest indications that these drugs have benefits for conditions beyond their original intended treatment of type 2 diabetes. 

Ozempic approved for reduced cardiovascular risk

Ozempic (semaglutide 0.5 mg, 1 mg, and 2 mg) previously received FDA approval for cardiovascular health in people with type 2 diabetes after combined results from the SUSTAIN-6 and PIONEER-6 trials showed a 24% reduction in major adverse cardiac events (MACE) such as heart attack, stroke, and other cardiovascular-related deaths. 

Rybelsus (oral semaglutide) was also FDA approved as a treatment to reduce cardiovascular risk. A handful of notable Novo Nordisk-sponsored studies have offered further evidence that medications such as semaglutide can offer additional benefits, including for heart health.

In addition to initial FLOW trial findings indicating Ozempic can offer kidney protective benefits, results of Novo Nordisk’s SELECT trial showed that semaglutide significantly reduced rates of kidney and cardiovascular events compared with placebo in participants with overweight and obesity with cardiovascular disease but without diabetes. In SELECT, Wegovy reduced the risk of MACE by 20% compared to the placebo group.

Following the success of the SELECT trial, Wegovy (semaglutide in doses of 1.7 mg and 2.4 mg) received a similar approval in March 2024 for people with overweight or obesity and cardiovascular disease.

Could Ozempic be used to treat liver disease in the future? 

Novo Nordisk has also been studying semaglutide in metabolic dysfunction-associated steatohepatitis (MASLD), a type of liver disease formerly known as nonalcoholic fatty liver disease, or NAFLD. 

Ongoing research is being conducted to see if semaglutide could also be used to treat additional conditions not specifically connected to diabetes, including osteoarthritis and joint pain; addictive disorders such as drug, alcohol, and tobacco use disorders; and obstructive sleep apnea.

FDA Headquarters
FDA headquarters.

The latest approved FDA labelings for Ozempic treatment

Originally approved only as a type 2 diabetes medication, once-weekly semaglutide labeling has expanded over recent years. It is now  approved for several conditions: 

  1. As a once-weekly injection in 0.5 mg, 1 mg, and 2 mg doses as an adjunct to diet and exercise for type 2 diabetes under the Ozempic label;
  2. As a once-weekly injection in 1.7 mg and 2.4 mg doses for obesity under the Wegovy label;
  3. As a once-weekly injection in 0.5 mg, 1 mg, and 2 mg doses to reduce cardiovascular events for people with type 2 diabetes under the Ozempic label
  4. As a once-weekly injection in 1.7 mg and 2.4 mg doses to reduce cardiovascular events for people with obesity and cardiovascular disease under the Wegovy label

Further reading:

Photo credits: Susannah Chen (Ozempic); iStock (all other photos).