Researchers found that people with type 2 diabetes have slightly more fluid in their blood compared to people without diabetes. Even more interesting, the type of diabetes medicine someone takes affects how much fluid is in their blood. Certain medications called SGLT2 inhibitors actually reduce this extra fluid, which could be good for heart health. Other medications called DPP-4 inhibitors increased the fluid levels. This discovery helps doctors understand why some diabetes medicines might protect the heart better than others.

The Quick Take

  • What they studied: Whether people with type 2 diabetes have different amounts of fluid in their blood compared to healthy people, and whether different diabetes medicines change these fluid levels.
  • Who participated: 638 adults with type 2 diabetes, compared with healthy adults of similar age, weight, and gender. The study looked at people taking different types of diabetes medications.
  • Key finding: People with type 2 diabetes had about 3.7% more fluid in their blood than healthy people. When taking SGLT2 inhibitor medications, this extra fluid decreased by 3.4%, and when combining two types of medications (SGLT2 inhibitors plus GLP-1 agonists), the fluid decreased by 6.5%.
  • What it means for you: If you have type 2 diabetes, your doctor may consider prescribing SGLT2 inhibitors, as these medications appear to have beneficial effects on blood fluid balance and heart health. However, this is one study, and you should discuss medication choices with your healthcare provider based on your individual health needs.

The Research Details

This was an observational study, meaning researchers watched and measured what naturally happened rather than randomly assigning people to different treatments. They compared blood fluid levels in people with type 2 diabetes to healthy people matched by age, weight, and gender. They also looked at a larger group of 638 people with diabetes to see how different diabetes medicines affected blood fluid levels. Blood fluid levels were calculated using a mathematical formula that considers how much red blood cells are in the blood, body weight, and whether someone is male or female.

Understanding how diabetes and different medicines affect the amount of fluid in blood is important because this fluid balance directly affects how well the heart works. Too much fluid in the blood can strain the heart and blood vessels. By studying this, researchers can better understand why some diabetes medicines might protect the heart better than others.

This study has moderate strength because it included a reasonably large group of 638 people with diabetes and compared them to matched healthy controls. However, because it’s observational rather than experimental, we can’t be completely certain that the medicines caused the changes in fluid levels—other factors could be involved. The study was published in a peer-reviewed medical journal, meaning other experts reviewed it before publication. The differences found were statistically significant, meaning they’re unlikely to be due to chance alone.

What the Results Show

People with type 2 diabetes had significantly more fluid in their blood (about 3.7% more) compared to healthy people of similar age and weight. This difference was small but real and unlikely to have happened by chance. Among people with diabetes, those taking SGLT2 inhibitor medications had noticeably less extra fluid in their blood compared to those only using diet and metformin (the standard treatment). The reduction was about 3.4%. When people took a combination of two medications—SGLT2 inhibitors plus GLP-1 agonists—the reduction was even larger at 6.5%. People taking only GLP-1 agonists showed a trend toward lower fluid levels, but this difference wasn’t quite large enough to be statistically significant. Interestingly, people taking DPP-4 inhibitor medications actually had more fluid in their blood, about 4.15% more than the standard treatment group. Insulin treatment didn’t show a significant difference compared to diet and metformin.

The study revealed that different classes of diabetes medications have different effects on blood fluid balance. This suggests that these medications work through different biological pathways and may have different impacts on heart health. The combination therapy (SGLT2 inhibitors plus GLP-1 agonists) showed the strongest beneficial effect on reducing extra blood fluid, suggesting that combining these medications might offer additional heart protection beyond what either medication alone provides.

Previous research has shown that expanded plasma volume (extra fluid in blood) is common in heart failure and chronic kidney disease. This study extends that knowledge by showing that type 2 diabetes is also associated with expanded plasma volume, though the increase is modest. The finding that SGLT2 inhibitors reduce plasma volume aligns with other research suggesting these medications have heart-protective benefits beyond just lowering blood sugar. This study adds to growing evidence that SGLT2 inhibitors may be particularly beneficial for people with diabetes who are at risk for heart problems.

This was an observational study, so we cannot prove that the medicines caused the changes in fluid levels—other factors could be responsible. The study measured fluid levels at one point in time rather than following people over months or years. The study didn’t measure whether these changes in fluid levels actually led to better heart health outcomes. The study population may not represent all people with diabetes, as different groups might respond differently. The study didn’t account for all possible factors that might affect blood fluid levels, such as diet, exercise, or other health conditions people might have.

The Bottom Line

If you have type 2 diabetes, SGLT2 inhibitor medications appear to have favorable effects on blood fluid balance and may offer heart protection. This finding supports considering SGLT2 inhibitors as a treatment option, particularly if you’re at risk for heart disease. The combination of SGLT2 inhibitors with GLP-1 agonists showed the strongest benefits. However, medication choices should always be made with your doctor based on your individual health situation, other medical conditions, and how you respond to treatment. This is one study, and more research is needed to confirm these findings and determine if the changes in fluid levels actually translate to better long-term health outcomes.

This research is most relevant for people with type 2 diabetes, especially those concerned about heart health or at risk for heart disease. Healthcare providers treating diabetes should be aware of these differential effects of various medications. People currently taking DPP-4 inhibitors should not stop their medication based on this single study but should discuss their treatment plan with their doctor. This research is less immediately relevant for people without diabetes, though it adds to our understanding of how diabetes affects the body.

Changes in blood fluid levels would likely occur relatively quickly after starting or changing medications, possibly within weeks to months. However, improvements in actual heart health outcomes would take longer to develop and measure, likely months to years. You shouldn’t expect to feel immediate differences, as changes in blood fluid balance don’t always cause noticeable symptoms.

Want to Apply This Research?

  • Track your diabetes medication type and dosage daily, along with weekly measurements of blood pressure and weight. These are indirect indicators of fluid balance and can help you and your doctor monitor how your current medication is working.
  • If your doctor prescribes an SGLT2 inhibitor, use the app to set reminders for taking your medication consistently and to track any side effects or changes you notice. Log your blood sugar readings to see how well the medication controls your diabetes, which is the primary goal of treatment.
  • Over the long term, use the app to track trends in blood pressure, weight, and blood sugar control. Share these trends with your doctor at regular appointments to evaluate whether your current medication is working well for you. If your doctor changes your medication, use the app to monitor any changes in these measurements over the following weeks and months.

This research describes associations between diabetes medications and blood fluid levels but does not prove that changes in fluid levels directly improve health outcomes. This study is observational and cannot establish cause-and-effect relationships. Do not change, start, or stop any diabetes medications based on this research alone. Always consult with your healthcare provider before making any changes to your diabetes treatment plan. This information is for educational purposes and should not replace professional medical advice. Individual responses to medications vary, and what works best depends on your specific health situation, other medical conditions, and other medications you may be taking.