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How is Dementia Tied to Diabetes Drugs?

Dementia is a condition that affects your memory and thinking capabilities. While dementia is usually thought of to be a part of the natural aging process, there are some conditions like diabetes that can increase the risk of someone developing dementia. The condition can be debilitating as the symptoms progress. In recent years, there has been a lot of research going on about how to prevent dementia and slow down cognitive decline in patients with this condition. Now, a new study has found that a type 2 diabetes medication known as glitazones can bring about a reduction of 22 percent in the risk of developing dementia. Here’s everything you need to know about dementia and diabetes drugs.

What is Dementia?

Dementia is a term used to refer to an overall decline in cognitive skills and memory. The disorder affects memory, thinking ability, and even social abilities in a severe way that disrupts your day-to-day life. While it is not one specific disease, but numerous diseases can cause dementia. Dementia can be a debilitating condition as it progresses. Alzheimer’s disease is the most commonly known cause of dementia in older people. Depending on the cause, signs, and symptoms of dementia can sometimes be reversible.(1234)

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How is Dementia Tied to Diabetes Drugs?

A new study has now found that a class of type 2 diabetes drugs known as glitazones can reduce the risk of developing dementia by 22 percent. However, since the study was not correlational, it did not find whether taking the medications was the primary reason for this observed risk reduction. It is interesting to note that researchers have identified that dementia and type 2 diabetes share several of the same physiological patterns.

The research was led by the University of Arizona in the US, and it was a long-term study that was published in October 2022 in the BMJ Open Diabetes Research and Care.(5) The study links the use of this type 2 diabetes drugs, known as glitazones, to a 22 percent reduced risk of developing dementia. Glitazones, also known as thiazolidinediones (TZDs), are an older family of drugs that doctors usually no longer prescribe for type 2 diabetes.(67)

Comparison of Glitazones With Metformin

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Since researchers believe that type 2 diabetes and dementia share several of the same physiological properties, many studies have been carried out to determine whether diabetes drugs can help in the treatment or at least delay the onset of dementia.(8) However, the problem is that the findings so far have remained inconsistent, due to which more research is being carried out.

In line with this, the research team from the University of Arizona carried out a comparison of dementia risk in older people who had type 2 diabetes and were treated with TZD or sulfonylurea, which is a very old class of drugs used to treat diabetes, as compared to those older adults who were being treated with metformin, which is the most widely prescribed diabetes drug used nowadays.(9)

During this study, the researchers looked at the online health records of over 555,000 people who were diagnosed with type 2 diabetes. The electronic data was accessed from the national Veteran Affairs (VA) Health System, and it ranged from January 2000 to December 2019. Most of the patients in the database were male, white, and over half of them were considered to be obese. All of them had type 2 diabetes. The research team carried out a comparison of the dementia risk among the participants aged 60 years or older who were being treated with either sulfonylurea or glitazone with those participants who were only given metformin during the period January 2001 to December 2017. The overall health of these individuals was then looked at for nearly eight years.

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The study found that individuals who were taking glitazone had an 11 percent lesser risk of developing Alzheimer’s disease and a 57 percent decreased risk of developing vascular dementia as compared to the participants who were only given metformin. The findings of the study also revealed that after just one year of treatment, taking TZD by itself led to a 22 percent reduced risk of dementia from any cause as compared to being treated with only the metformin drug. It is important to note that when most patients are diagnosed with mild cognitive impairment, which is usually the precursor to Alzheimer’s disease, there is a 30 percent risk that they will go on to develop full dementia. If such a patient also has type 2 diabetes, they may benefit by immediately switching to using TZD as their treatment, as it can bring about a 22 percent decline in this risk.

Younger People to Experience More Benefits From Diabetes Drugs

The researchers also discovered that the risk for dementia caused by any reason was 11 percent lower when using a TZD medicine and metformin together. This suggested that another option to reduce the risk of dementia is to supplement sulfonylurea with metformin. At the same time, further analysis of the data unfolded a surprising piece of information that people below the age of 75 years actually experienced more benefits from using a TZD drug than older patients.

This finding highlights the importance of starting early dementia prevention. The study also indicated another surprising fact that these drugs can be more protective and have better benefits for patients who are obese or overweight.

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Why Does This Happen?

One theory behind why diabetes drugs can lower the risk of dementia in people with type 2 diabetes is that because of vascular disease, the body’s blood-brain barrier becomes more porous, which allows more viruses or infections to cross over into the brain, thus leading to the brain changes often observed in people with Alzheimer’s disease. So by, reducing these vascular changes in the brain, it might decrease the risk factors for dementia or conditions like Alzheimer’s that cause dementia.

One of the reasons why many patients with type 2 diabetes do not like to use TZDs is because these drugs can lead to weight gain, even though it is minimal and mostly water weight. However, TZDs offer many important benefits to patients, especially when you check the results of the A1C test, which looks at your three-month average blood sugar levels.(1011) This class of drugs does not cause hypoglycemia, and the reduction in the A1C levels is also quite a lot.

The researchers concluded that even though TZDs may not provide any cardiovascular benefits like metformin offers, the significant reduction in the risk of dementia is essential enough for doctors to start prescribing this class of drugs again, especially in high-risk individuals.

Conclusion

One thing that has to be kept in mind, though, is that this study was just observational, which means that it did not prove that the drug caused the reduced risk but found that the TZDs drugs were linked with the reduction. This is why there is a need to conduct placebo-controlled and double-blind clinical trials to confirm whether this drug can actually help decrease the risk of dementia in people with and without type 2 diabetes. You can always ask your doctor for more information on whether changing your medication may help if you are at a high risk of developing dementia or if you have a family history of the condition.

References:

  1. Geldmacher, D.S. and Whitehouse, P.J., 1996. Evaluation of dementia. New England Journal of Medicine, 335(5), pp.330-336.
  2. Kitwood, T., 1997. The experience of dementia. Aging & mental health, 1(1), pp.13-22.
  3. Mendez, M.F. and Cummings, J.L., 2003. Dementia: a clinical approach. Butterworth-Heinemann.
  4. Chen, J.H., Lin, K.P. and Chen, Y.C., 2009. Risk factors for dementia. Journal of the Formosan Medical Association, 108(10), pp.754-764.
  5. Tang, X., Brinton, R.D., Chen, Z., Farland, L.V., Klimentidis, Y., Migrino, R., Reaven, P., Rodgers, K. and Zhou, J.J., 2022. Use of oral diabetes medications and the risk of incident dementia in US veterans aged≥ 60 years with type 2 diabetes. BMJ Open Diabetes Research and Care, 10(5), p.e002894.
  6. Daniel, K., 2000. The glitazones: proceed with caution. Western Journal of Medicine, 173(1), p.54.
  7. Arnold, S.V., Inzucchi, S.E., Echouffo-Tcheugui, J.B., Tang, F., Lam, C.S., Sperling, L.S. and Kosiborod, M., 2019. Understanding contemporary use of thiazolidinediones: an analysis from the diabetes collaborative registry. Circulation: Heart Failure, 12(6), p.e005855.
  8. Alagiakrishnan, K., Sankaralingam, S., Ghosh, M., Mereu, L. and Senior, P., 2013. Antidiabetic drugs and their potential role in treating mild cognitive impairment and Alzheimer’s disease. Discovery medicine, 16(90), pp.277-286.
  9. Costello, R.A., Nicolas, S. and Shivkumar, A., 2022. Sulfonylureas. In StatPearls [Internet]. StatPearls Publishing.
  10. Eyth, E. and Naik, R., 2019. Hemoglobin A1C.
  11. Sacks, D.B., 2011. A1C versus glucose testing: a comparison. Diabetes care, 34(2), pp.518-523.

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