Ozempic Slows Kidney Disease, Cuts Death Risk in Type 2 Diabetes

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.
• Patients who took Ozempic versus placebo also cut their risk of major heart problems by 18%.
• The latest: A new analysis showed that semaglutide also reduced the chances of experiencing heart failure or death from cardiovascular causes.

Those 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.

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 one’s 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 heart attack, non-fatal stroke, or cardiovascular death.

A new analysis from the FLOW trial was presented this week at EASD 2024, which looked at the effects of semaglutide on heart failure in people with type 2 diabetes and CKD. The data showed that once-weekly 1 mg doses of semaglutide were shown to reduce the likelihood of  a first-time heart failure event, urgent visits or hospitalizations due to heart failure, or cardiovascular death.

More specifically, data showed that semaglutide decreased the overall likelihood of the following, regardless of the severity of diabetes-related kidney disease: 

• Either serious heart failure for the first time or cardiovascular death, by 27%
• Heart failure events, by 27%
• Cardiovascular death, by 29%

Positive effects were consistent, regardless of history of heart failure; even people without heart failure were less likely to develop it during the trial.

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.

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. Based on the results, Novo Nordisk, the Danish drugmaker behind Ozempic, said it was filing for expanded indications for Ozempic in the U.S. and in the European Union in 2024.

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.

Given the success of the FLOW trial, Novo Nordisk has said that it has filed for expanded indications 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 and expects to hear about the filing sometime this year.

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

The results of the trial could expand Ozempic’s (and eventually other GLP-1 receptor agonists’) indications to treat many more conditions for people with type 2 diabetes.

“Semaglutide saves kidneys, hearts, and lives,” Dr. Katherine Tuttle, executive director for Research Providence Inland Northwest Health in Spokane and one of the substudy’s lead authors, said. 

Ozempic expected to also become treatment for kidney disease

These positive study results set the stage for Ozempic – and eventually some of the other drugs in the same class – to become a treatment option for chronic kidney disease in those with type 2 diabetes.

“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 for type 2 diabetes  and Zepbound for obesity) can treat CKD in people with obesity or 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 will likely be used in the future to improve heart failure outcomes

The key objective of the trial was related to delaying kidney disease; however, because data showed that semaglutide was so clearly effective in improving heart failure and mortality outcomes in a high-risk population of people with type 2 diabetes and CKD, Ozempic will also likely become a treatment option for heart failure, too.

Diabetes, chronic kidney disease, and heart failure can go hand in hand: Having both type 2 diabetes and CKD can increase the risk of heart failure and death compared to having each condition on its own.

“People with type 2 diabetes and CKD are very high-risk for heart failure,” Tuttle said.  She also noted that there’s a critical need for more effective therapies for heart failure. 

“We have to look at patients holistically, who have kidney disease and diabetes, to address the totality of risks, certainly progression to kidney failure, but also prevention of cardiovascular events and deaths.”

Ozempic and other GLP-1s will 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 an even 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?

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.

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.”

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 other 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 to reduce 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, including osteoarthritis, joint pain, and drug, alcohol, and tobacco related addictive disorders.

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:

• Chronic Kidney Disease: The Hidden Complication
• Studies Suggest Diabetes Drugs Help Hearts and Kidneys for People With or Without Diabetes
• Diabetes Remission Reduces Risk of Heart and Kidney Disease
• Keeping Your Heart and Kidneys Healthy When You Have Diabetes

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