Key messages

• For people with chronic kidney disease (CKD) (long-term damage to the kidneys that reduces their ability to filter blood), also having diabetes (a lifelong condition that causes a person's blood sugar level to become too high) increases the chances of early death, heart attack, stroke and reduces a person's quality of life.

• It is unclear whether dipeptidyl peptidase 4 (DPP-4) inhibitors (medication that reduces blood sugar levels) prevent death due to a heart problem, severe hypoglycaemic events (a condition where the blood glucose level drops too low, causing symptoms like shakiness, dizziness, and sweating), or prevent heart or kidney complications in people with CKD and type 2 diabetes.

• It is unclear whether DPP-4 inhibitors have similar benefits or harms compared to other medications for people with CKD and type 2 diabetes.

Why treat people with chronic kidney disease and type 2 diabetes with DPP-4?

Dipeptidyl peptidase 4 (DPP-4) inhibitors are medications that reduce blood glucose levels and are now recommended as second-line treatment for people with type 2 diabetes (a lifelong condition that causes a person's blood sugar level to become too high) and chronic kidney disease (CKD, defined as long-term damage to the kidneys that reduces their ability to filter blood) whose type 2 diabetes is not adequately controlled by their current medications.

What did we want to find out?

We wanted to find out whether DPP-4 inhibitors help to prevent blood vessel and kidney complications for people who have both CKD and type 2 diabetes.

What did we do?

We explored whether DPP-4 inhibitors prevent people from getting complications such as death due to heart-related causes, severe hypoglycaemia (a condition where the blood glucose level drops too low, causing symptoms like shakiness, dizziness, and sweating), any circulation problems, heart attack, stroke, or kidney problems when they have both low kidney function and type 2 diabetes. We searched for all available randomised clinical studies (studies in which people are randomly assigned to different treatment options) to determine whether this type of medication is effective in preventing these complications. We also assessed our confidence in the results of the available research studies.

What did we find?

We identified 59 clinical studies involving 27,893 adults with CKD and diabetes. Participants in the studies received a DPP-4 inhibitor, a placebo (sugar pill), standard care alone, or another diabetes medication (e.g. insulin). The treatment they received was decided by random chance (like tossing a coin). We found no studies that involved children.

Combining all the studies, we found that we still don't know whether treatment with DPP-4 inhibitors helps to lower a person's chances of death due to heart-related causes or severe hypoglycaemia. We cannot be sure whether treatment prevents any circulation problems, including a heart attack or stroke, or kidney problems, because we did not find enough information in the available studies. We also could not be sure whether DPP-4 inhibitor medication was better or worse than other treatments for diabetes, as this was not extensively studied in the clinical trials.

What are the limitations of the evidence?

Some of the studies were difficult to use, had very small sample sizes, or were followed for only a short duration, and, as a result, we are less sure about whether treatment causes side effects. In general, the effects of DPP-4 inhibitors in people with CKD and type 2 diabetes were insufficient to provide firm conclusions.

How up to date is the evidence?

The evidence is current to March 2025.