Diabetes warning: Common drug may increases risk of fathering boys with birth defects

Type 2 diabetes can be a 'devastating diagnosis' says expert

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Diabetes is a condition in which an individual’s blood sugar levels become too high as a result of a problem with insulin, the hormone which regulates glucose levels in the blood. There are two main types – in type 1, the body’s immune system attacks and destroys insulin-producing cells, while in type 2 the body either does not produce enough insulin or its cells fail to react to it properly. With type 1 diabetes typically manifesting during childhood, and type 2 or ‘adult-onset’ diabetes becoming more and more common in younger adults, the prevalence of the condition is increasing among adults of a reproductive age. Diabetes is known to compromise sperm quality and male fertility.

However, a study, currently being reviewed by the Medicines and Healthcare products Regulatory Agency, has suggested that some diabetic medications — specifically metformin, the first-line defence against type 2 diabetes — may also influence semen development and testosterone levels.

In their new study, public health researcher Professor Maarten Wensink of the University of Southern Denmark and his colleagues studied the outcomes from 1,116,779 births in Denmark between 1997 and 2006.

The team used national health databases to evaluate incidences of birth defects among the children and compare such to the use of three common diabetes drugs — insulin, metformin and sulfonylureas — by their fathers.

Injected insulin serves as a replacement for or supplement to the body’s natural supply. Metformin, meanwhile, lowers glucose production in the liver and makes the body more sensitive to insulin, whereas sulfonylureas stimulate the pancreas to make more insulin.

The researchers considered the children to have been exposed to these drugs if their father filled at least one insulin, metformin or sulfonylureas prescription during the three-month period prior to conception in which the fertilising sperm were developing.

The researchers found that babies whose fathers had been taking insulin had the same risk of birth defects as those taking no diabetes medications.

However, the same could not be said for those born to fathers taking metformin, according to the study.

The team wrote: “Preconception paternal metformin treatment is associated with major birth defects, particularly genital birth defects in boys.”

In fact, their analysis suggested that children born to metformin-taking fathers had a 40 percent higher risk of birth defects.

There was insufficient data on fathers who took sulfonylureas to evaluate their risk with any certainty, the researchers noted.

The researchers wrote: “The sheer size of the diabetes pandemic suggests that treatment of prospective fathers with diabetes, including pharmacologic management and counselling on diet, physical exercise, and weight loss, should be subject to further study.”

While halting metformin usage may lower the risk of birth defects, the resulting impact on diabetes control could have other impacts on sperm quality that might need evaluating.

The team added: “Further research should replicate the findings while accounting for glycaemic control and other metabolic features, and expose the underlying pathway.”

The team found that children born to fathers who took metformin before or after the three-month sperm production window were not at a higher risk of birth defects.

Similarly, unexposed siblings were also not found to be at a higher risk.

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The researchers wrote: “The sheer size of the diabetes pandemic suggests that treatment of prospective fathers with diabetes, including pharmacologic management and counselling on diet, physical exercise, and weight loss, should be subject to further study.”

While halting metformin usage may lower the risk of birth defects, the resulting impact on diabetes control could have other impacts on sperm quality that might need evaluating.

The team added: “Further research should replicate the findings while accounting for glycaemic control and other metabolic features, and expose the underlying pathway.”

The team found that children born to fathers who took metformin before or after the three-month sperm production window were not at a higher risk of birth defects.

Similarly, unexposed siblings were also not found to be at a higher risk.

The full findings of the study were published in the journal Annals of Internal Medicine.

In an associated editorial, reproductive and perinatal epidemiologist Dr Germaine Louis of the George Mason University in Virginia — who was not involved in the study — said: “Given the prevalence of metformin use as first-line therapy for type 2 diabetes, corroboration of these findings is urgently needed.

“Meanwhile, clinical guidance is needed to help couples planning pregnancy weigh the risks and benefits of paternal metformin use relative to other medications.

“Important in this guidance will be communicating that the adverse relationship was specific to metformin during the period of spermatogenesis.”

Metformin is currently available on the NHS with a prescription as tablets, as a liquid that you swallow and as sachets of powder that you dissolve in a drink.

MHRA told Express.co.uk: “The MHRA is carefully reviewing the findings of this study and will communicate further as necessary.”

“Patients should continue taking metformin.

“The benefits of using metformin to treat type 2 diabetes mellitus continue to outweigh the recognised risks or side-effects of treatment.

“Patients should not stop taking their prescribed medication without first discussing their treatment with their doctor.”

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