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Metformin in Type 1 Patients Slows Development of Heart Disease

Scientists believe drug commonly prescribed for T2 could be routinely taken by T1 patients.

Metformin is an inexpensive treatment that is often used for type 2 diabetes to lower blood glucose levels by reducing glucose production in the liver.

Normally the drug is not regularly given to patients with type 1 diabetes. However, for the first time, a clinical trial has revealed metformin can increase vascular stem cells, which can promote a patient’s ability to repair their own damaged blood vessels.

Metformin may be used to lower risk of developing heart disease in patients who have type 2 diabetes, which is the leading cause of illness in type 1 diabetes, accounting for more than half of all fatalities.

Dr. Jolanta Weaver, Senior Lecturer in Diabetes Medicine at Newcastle, led two of the studies and believes this new research is a major development in understanding the best ways to further improve treatment in type 1 diabetes.

She added that, “As the outcomes of heart disease is worse in diabetic versus nondiabetes patients, there is a need to identify additional treatment options. Metformin could routinely be used by patients with type 1 diabetes to help lower their chances of developing heart disease, by increasing a repair mechanism created by vascular stem cells released from the bone marrow. For the first time, this study has shown metformin has additional benefit beyond improving diabetes control when given to patients with relatively well controlled type 1 diabetes. We have established the drug increases patient’s own vascular stem cells, which will help delay or slowdown heart disease. Our research is an exciting step forward as it may have positive clinical implications for patients with increased risk of cardiovascular disease by improving their treatment options.” The findings show that the cells associated with damaged blood vessels were reduced, confirming that the repair of blood vessels was taking place.

Researchers studied a treatment group of 23 people ages 19-64 who had type 1 diabetes for up to 23 years and no evidence of heart disease. Patients were given metformin at a dose they could tolerate, between one to three tablets a day, for eight weeks. Participants were advised to adjust their insulin to keep blood glucose levels safe. They measured patients’ stem cells directly in the blood and also grew stem cells in a test tube, observing how they behaved. Another cell type was also counted to assess damaged blood vessels.

For the control group, the participants were matched with nine patients within the same age bracket who took standard insulin treatment and 23 healthy people without diabetes ages 20-64. Experts found that the stem cells of patients who took metformin were able to promote the repair of the blood vessels and there was an improvement in how vascular stem cells worked.

The study showed that all the patients in the study had their insulin doses reduced after taking metformin and have not suffered any serious adverse effect.

The results, which indicate that metformin, a drug commonly used in the treatment of type 2 diabetes, could also have a powerful effect in people with type 1 diabetes is unexpected.

In another study, metformin showed that it was able to improve circulating endothelial cells and endothelial progenitor cells in type 1 diabetes (MERIT study).  This study was an open label and parallel standard treatment study. Twenty-three type 1 diabetes patients without overt CVD were treated with metformin for 8 weeks (treatment group-TG). They were matched with nine type 1 diabetes patients on standard treatment (SG) and 23 age- and sex-matched healthy volunteers (HC). The insulin dose was adjusted to keep unchanged glycemic control.

From the results, it was concluded that metformin has potential cardioprotective effects through improving cEPCs (endothelial progenitor cells), CFU-Hill’s colonies, cECs (decreasing circulating endothelial cells), PACs (pro-angiogenic cells) count and functioning independently of hypoglycemic effect.

The study has shown for the first time that metformin treatment may result in cardiovascular benefit by increasing markers of vascular repair or health (cEPCs, CFU-Hill’s colonies, and PACs) and reducing markers of vascular damage (cECs).

In this study, it was demonstrated for the first time that in patients with relatively well controlled type 1 diabetes mellitus (mean HbA1c 7.3 or 56.4 mmol/mol), metformin therapy improved markers of vascular damage and repair. The authors believe that this study may have positive clinical implications for patients with increased CVD risk by rebalancing the emphasis in their management from limiting damage alone to also improving vascular repair.

The additional benefit suggested by this study for patients with type 1 diabetes is that the vascular health/repair may be improved in already well-controlled patients and without a need for further improvement in glycemic control. Patients with type 1 diabetes are currently advised to achieve HbA1c <7 % or <54 mmol/mol in order to reduce CVD events. However, this is associated with inherent risk of experiencing hypoglycemia. Thus, an additional advantage of using metformin in type 1 diabetes suggested by our study is that markers of vascular health and repair may be improved without lowering blood glucose concentrations to a tightly control HbA1c level.

Practice Pearls:

  • Metformin treatment may result in cardiovascular benefit.
  • Using metformin in type 1 diabetes, markers of vascular health and repair may be improved without lowering blood glucose concentrations to a tightly control HbA1c level.
  • Metformin was able to improve circulating endothelial cells and endothelial progenitor cells in type 1 diabetes (MERIT study).

References:

Michael Glanville, Kilimangalam Narayanan, Salman Razvi and Jolanta U Weaver, Cardiovascular Diabetology, doi: 10.1186/s12933-016-0413-6, published 26 August 2016. Cardiovascular Diabetology. 201615:116  DOI: 10.1186/s12933-016-0413-6

 

Researched and prepared by Pablo A. Marrero-Núñez – USF College of Pharmacy Student Delegate –  Doctor of Pharmacy Candidate 2017 – University of South Florida – College of Pharmacy