Semaglutide (sold as Ozempic, Wegovy and Rybelsus) was initially developed to treat diabetes. It works by stimulating the production of insulin to keep blood sugar levels in check.

This type of drug is increasingly being prescribed for weight loss, despite the fact it was initially approved for another purpose. Recently, there has been growing interest in another possible use: to treat addiction.

Anecdotal reports from patients taking semaglutide for weight loss suggest it reduces their appetite and craving for food, but surprisingly, it also may reduce their desire to drink alcohol, smoke cigarettes or take other drugs.

But does the research evidence back this up?

Animal studies show positive results

Semaglutide works on glucagon-like peptide-1 receptors and is known as a “GLP-1 agonist”.

Animal studies in rodents and monkeys have been overwhelmingly positive. Studies suggest GLP-1 agonists can reduce drug consumption and the rewarding value of drugs, including alcohol, nicotine, cocaine and opioids.

Out team has reviewed the evidence and found more than 30 different pre-clinical studies have been conducted. The majority show positive results in reducing drug and alcohol consumption or cravings. More than half of these studies focus specifically on alcohol use.

However, translating research evidence from animal models to people living with addiction is challenging. Although these results are promising, it’s still too early to tell if it will be safe and effective in humans with alcohol use disorder, nicotine addiction or another drug dependence.

What about research in humans?

Research findings are mixed in human studies.

Only one large randomised controlled trial has been conducted so far on alcohol. This study of 127 people found no difference between exenatide (a GLP-1 agonist) and placebo (a sham treatment) in reducing alcohol use or heavy drinking over 26 weeks.

In fact, everyone in the study reduced their drinking, both people on active medication and in the placebo group.

However, the authors conducted further analyses to examine changes in drinking in relation to weight. They found there was a reduction in drinking for people who had both alcohol use problems and obesity.

For people who started at a normal weight (BMI less than 30), despite initial reductions in drinking, they observed a rebound increase in levels of heavy drinking after four weeks of medication, with an overall increase in heavy drinking days relative to those who took the placebo.

There were no differences between groups for other measures of drinking, such as cravings.

In another 12-week trial, researchers found the GLP-1 agonist dulaglutide did not help to reduce smoking.

However, people receiving GLP-1 agonist dulaglutide drank 29% less alcohol than those on the placebo. Over 90% of people in this study also had obesity.

Smaller studies have looked at GLP-1 agonists short-term for cocaine and opioids, with mixed results.

There are currently many other clinical studies of GLP-1 agonists and alcohol and other addictive disorders underway.

While we await findings from bigger studies, it’s difficult to interpret the conflicting results. These differences in treatment response may come from individual differences that affect addiction, including physical and mental health problems.

Larger studies in broader populations of people will tell us more about whether GLP-1 agonists will work for addiction, and if so, for whom.

How might these drugs work for addiction?

The exact way GLP-1 agonists act are not yet well understood, however in addition to reducing consumption (of food or drugs), they also may reduce cravings.

Animal studies show GLP-1 agonists reduce craving for cocaine and opioids.

This may involve a key are of the brain reward circuit, the ventral striatum, with experimenters showing if they directly administer GLP-1 agonists into this region, rats show reduced “craving” for oxycodone or cocaine, possibly through reducing drug-induced dopamine release.

Using human brain imaging, experimenters can elicit craving by showing images (cues) associated with alcohol. The GLP-1 agonist exenatide reduced brain activity in response to an alcohol cue. Researchers saw reduced brain activity in the ventral striatum and septal areas of the brain, which connect to regions that regulate emotion, like the amygdala.

In studies in humans, it remains unclear whether GLP-1 agonists act directly to reduce cravings for alcohol or other drugs. This needs to be directly assessed in future research, alongside any reductions in use.

Are these drugs safe to use for addiction?

Overall, GLP-1 agonists have been shown to be relatively safe in healthy adults, and in people with diabetes or obesity. However side effects do include nausea, digestive troubles and headaches.

And while some people are OK with losing weight as a side effect, others aren’t. If someone is already underweight, for example, this drug might not be suitable for them.

In addition, very few studies have been conducted in people with addictive disorders. Yet some side effects may be more of an issue in people with addiction. Recent research, for instance, points to a rare risk of pancreatitis associated with GLP-1 agonists, and people with alcohol use problems already have a higher risk of this disorder.

Other drugs treatments are currently available

Although emerging research on GLP-1 agonists for addiction is an exciting development, much more research needs to be done to know the risks and benefits of these GLP-1 agonists for people living with addiction.

In the meantime, existing effective medications for addiction remain under-prescribed. Only about 3% of Australians with alcohol dependence, for example, are prescribed medication treatments such as like naltrexone, acamprosate or disulfiram. We need to ensure current medication treatments are accessible and health providers know how to prescribe them.

Continued innovation in addiction treatment is also essential. Our team is leading research towards other individualised and effective medications for alcohol dependence, while others are investigating treatments for nicotine addiction and other drug dependence.

Read the other articles in The Conversation’s Ozempic series here.

Shalini Arunogiri, Addiction Psychiatrist, Associate Professor, Monash University; Leigh Walker, , Florey Institute of Neuroscience and Mental Health, and Roberta Anversa, , The University of Melbourne

This article is republished from The Conversation under a Creative Commons license. Read the original article.

We hear a lot about women’s biological clock and how age affects the chance of pregnancy.

New research shows men’s fertility is also affected by age. When dads are over 50, the risk of pregnancy complications increases.

Data from more than 46 million births in the United States between 2011 and 2022 compared fathers in their 30s with fathers in their 50s.

While taking into account the age of the mother and other factors known to affect pregnancy outcomes, the researchers found every ten-year increase in paternal age was linked to more complications.

The researchers found that compared to couples where the father was aged 30–39, for couples where the dad was in his 50s, there was a:

• 16% increased risk of preterm birth
• 14% increased risk of low birth weight
• 13% increase in gestational diabetes.

The older fathers were also twice as likely to have used assisted reproductive technology, including IVF, to conceive than their younger counterparts.

Dads are getting older

In this US study, the mean age of all fathers increased from 30.8 years in 2011 to 32.1 years in 2022.

In that same period, the proportion of men aged 50 years or older fathering a child increased from 1.1% to 1.3%.

We don’t know the proportion of men over 50 years who father children in Australia, but data shows the average age of fathers has increased.

In 1975 the median age of Australian dads was 28.6 years. This jumped to 33.7 years in 2022.

How male age affects getting pregnant

As we know from media reports of celebrity dads, men produce sperm from puberty throughout life and can father children well into old age.

However, there is a noticeable decline in sperm quality from about age 40.

Female partners of older men take longer to achieve pregnancy than those with younger partners.

A study of the effect of male age on time to pregnancy showed women with male partners aged 45 or older were almost five times more likely to take more than a year to conceive compared to those with partners aged 25 or under. More than three quarters (76.8%) of men under the age of 25 years impregnated their female partners within six months, compared with just over half (52.9%) of men over the age of 45.

Pooled data from ten studies showed that partners of older men are also more likely to experience miscarriage. Compared to couples where the male was aged 25 to 29 years, paternal age over 45 years increased the risk of miscarriage by 43%.

Older men are more likely to need IVF

Outcomes of assisted reproductive technology, such as IVF, are also influenced by the age of the male partner.

A review of studies in couples using assisted reproductive technologies found paternal age under 40 years reduced the risk of miscarriage by about 25% compared to couples with men aged over 40.

Having a male under 40 years also almost doubled the chance of a live birth per treatment cycle. With a man over 40, 17.6% of treatment rounds resulted in a live birth, compared to 28.4% when the male was under 40.

How does male age affect the health outcomes of children?

As a result of age-related changes in sperm DNA, the children of older fathers have increased risk of a number of conditions. Autism, schizophrenia, bipolar disorders and leukaemia have been linked to the father’s advanced years.

A review of studies assessing the impact of advanced paternal age reported that children of older fathers have increased rates of psychiatric disease and behavioural impairments.

But while the increased risk of adverse health outcomes linked to older paternal age is real, the magnitude of the effect is modest. It’s important to remember that an increase in a very small risk is still a small risk and most children of older fathers are born healthy and develop well.

Improving your health can improve your fertility

In addition to the effects of older age, some chronic conditions that affect fertility and reproductive outcomes become more common as men get older. They include obesity and diabetes which affect sperm quality by lowering testosterone levels.

While we can’t change our age, some lifestyle factors that increase the risk of pregnancy complications and reduce fertility, can be tackled. They include:

• smoking
• recreational drug taking
• anabolic steroid use
• heavy alcohol consumption.

Get the facts about the male biological clock

Research shows men want children as much as women do. And most men want at least two children.

Yet most men lack knowledge about the limitations of female and male fertility and overestimate the chance of getting pregnant, with and without assisted reproductive technologies.

We need better public education, starting at school, to improve awareness of the impact of male and female age on reproductive outcomes and help people have healthy babies.

For men wanting to improve their chance of conceiving, the government-funded sites Healthy Male and Your Fertility are a good place to start. These offer evidence-based and accessible information about reproductive health, and tips to improve your reproductive health and give your children the best start in life.

Karin Hammarberg, Senior Research Fellow, Global and Women’s Health, School of Public Health & Preventive Medicine, Monash University

This article is republished from The Conversation under a Creative Commons license. Read the original article.