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 thiazolidinediones (drugs that reduce blood sugar levels) prevent death due to a heart problem or 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 thiazolidinediones have similar benefits and harms compared to other drugs for diabetes in people with CKD and type 2 diabetes.

Why treat people with chronic kidney disease and type 2 diabetes with thiazolidinediones?

Thiazolidinediones are medications that reduce blood glucose levels and are now used to help people with chronic kidney disease (CKD: defined as long-term damage to the kidneys that reduces their ability to filter blood) and type 2 diabetes.

What did we want to find out?

We wanted to find out whether thiazolidinediones help to prevent death, heart and kidney complications for people who have both CKD and type 2 diabetes.

What did we do?

We explored whether thiazolidinediones prevent people from getting complications such as death, heart attack, stroke, hypoglycaemic (a condition where the blood glucose level drops too low, causing symptoms like shakiness, dizziness, and sweating) events, kidney problems or other circulation 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 found 85 clinical studies involving 3044 people with a kidney condition and type 2 diabetes. People in the studies took a thiazolidinedione drug, or a sugar pill (placebo), standard care alone, different doses of thiazolidinedione drugs, or a different diabetes medication (e.g. insulin or metformin). The treatment they received was decided by random chance (much like tossing a coin). Only one study involved children.

Combining all the studies, we found that we still don't know whether treatment with thiazolidinediones helps to lower a person's chances of death directly due to a heart problem or severe hypoglycaemic events, defined as blood sugar (glucose) levels lower than the standard range that required third-party assistance. We cannot be sure whether treatment prevents death, heart attack, stroke, problems with very low blood sugar levels, or kidney problems because we did not find information in the available studies to be sure. We could also not be sure whether thiazolidinedione drugs were better or worse than other treatments for diabetes or the effects of different doses, as this was not extensively studied in clinical trials.

What are the limitations of the evidence?

Some of the information in the studies was difficult to use or provided low-quality data, and as a result, we are less sure about whether treatment causes side effects. Insufficient data were reported in people with advanced kidney failure. In general, the effects of thiazolidinediones in people with CKD and type 2 diabetes were insufficient to provide firm conclusions. Future studies will address the benefits and harms of thiazolidinediones in this setting, reporting the core outcomes as prioritised by stakeholders to better inform decision-making.

How up to date is the evidence?

The evidence is current to October 2024.