Medications for type 2 diabetes and chronic kidney disease

Diabetes medications that directly benefit the kidneys

The U.S. Food and Drug Administration (FDA) has approved two classes of medications for the management of type 2 diabetes that have direct and significant benefits on kidney health: sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists.

SGLT2 inhibitors

SGLT2 inhibitors are daily pills that block the body’s ability to reabsorb sugar (glucose) from the blood, causing excess sugar to leave the body through urine.

Originally, these drugs were intended to help lower blood sugar levels in people with type 2 diabetes. But long-term studies have also found that SGLT2 inhibitors offer significant protection for kidney and heart health. Some of these studies were stopped prematurely because the evidence for kidney benefits was so overwhelming that it was unethical to continue giving a placebo (a dummy treatment) to volunteers with diabetes and CKD in the control group.

These trials have found that SGLT2 inhibitors can slow the deterioration of kidney function by up to 60 percent, significantly delaying the development of serious outcomes such as kidney failure and premature death.

SGLT2 inhibitors can be prescribed to people in most stages of CKD, including those with advanced kidney failure or at high risk of kidney failure: “People with advanced CKD but not yet on dialysis may also benefit,” it says Alejandro Turchin, MDdirector of diabetes quality at Brigham and Women’s Hospital and associate professor at Harvard Medical School in Boston, Massachusetts.

It is less clear whether or not SGLT2 inhibitors protect kidney health in people who have not yet developed measurable kidney disease, as this has not yet been rigorously tested. “But based on what we know so far, its use could reasonably be expected to have benefits for kidney health,” says Dr. Turchin.

SGLT2 inhibitors on the market approved for the treatment or prevention of kidney disease include:

canagliflozin (Invokana)
dapagliflozin (Farxiga)
empagliflozin (Jardiance)

Common side effects include:

Dehydration
Urinate more frequently
Fungal infections and urinary tract infections (UTI)
low blood pressure
low blood sugar

In addition to their kidney benefits, SGLT2 inhibitors may help protect the heart and blood vessels by lowering blood pressure. That can reduce the risk of major cardiac events and hospitalizations for heart failure. SGLT2 inhibitors are generally safe for people with kidney problems, in whom many medications cause adverse effects.

GLP-1 receptor agonists

GLP-1 receptor agonists are best known as blockbuster medications for diabetes and obesity. They mimic a hormone that triggers the release of insulin from the pancreas to promote digestion and slow the release of glucose from the liver to control blood sugar. They also increase the feeling of satiety after meals and slow digestion.

GLP-1 can improve kidney health by keeping blood sugar levels within the target range and triggering weight loss. They may also reduce kidney inflammation or remove excess sodium from the body, but more research is needed to confirm direct effects.

Although there are several GLP-1 medications on the market, only one has been approved for the treatment of kidney disease in people with type 2 diabetes: semaglutide (Ozempic).

In a major trial, semaglutide significantly slowed the rate of decline in kidney function, reduced the risk of major kidney or cardiovascular events by 24 percent, and reduced the risk of death by 20 percent.

Preliminary evidence suggests that tirzepatide (Mounjaro) also protects kidney function, but researchers have not yet completed the long, rigorous trials needed to fully test the drug’s effect on kidney disease.

Although the evidence for kidney protection may be stronger for SGLT2 inhibitors than for GLP-1, it is not really known whether one drug is more effective than the other: “No one has compared them directly to each other, but SGLT2 inhibitors appear to be more effective in preventing [the] progression of kidney disease than GLP1,” says Turchin.

And it is possible to take both at the same time, he says. “I wouldn’t normally consider it a choice between the two. From what we know, combining both classes of medications may result in greater benefit, although, again, the evidence has not yet examined this. I generally recommend that my patients with kidney disease take both to prevent disease progression as much as possible.”

Semaglutide (Ozempic), the long-acting GLP-1 approved by the FDA to treat type 2 diabetes and CKD, is available as a weekly injection. The most common side effects are gastrointestinal symptoms, including nausea, vomiting, and diarrhea. If you are already using glucose-lowering medications such as insulin, your dose may need to be changed when starting semaglutide.