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Disease and treatment

Drugs used to treat diabetes and obesity can reduce the urge to drink alcohol

Alcohol misuse is a massive social problem, causing 6% of deaths globally according to the World Health Organization. Pharmaceutical treatment of alcohol use disorder has scarcely changed in the past 25 years because developing and approving new treatments is both difficult and expensive. Researchers have now discovered that a drug already approved for treating diabetes also reduces the urge to drink alcohol.

Monkeys on Saint Kitts, an island in the Caribbean, are famous for voluntarily drinking large quantities of alcohol. This makes them ideal candidates for studying alcohol use disorder, which represents a major problem for people. Now Danish researchers have attempted to use a completely new and very surprising intervention to reduce the monkeys’ desire to drink alcohol: glucagon-like peptide-1 (GLP-1) analogues, drugs that are normally used to treat diabetes and obesity.

“The monkeys’ alcohol intake declined by 20–30% when they were given this drug. A possible cause may be that it inhibits the secretion of dopamine in the brain, resulting in the alcohol not providing the monkeys the same feelings of happiness as it would otherwise. Since GLP-1 analogues are already approved for treating people for diabetes and/or obesity, the path to an additional indication – alcohol use disorder – is actually shorter than if the drugs had not previously been used clinically,” explains a main author, Anders Fink-Jensen, Consultant, Mental Health Services, Capital Region of Denmark and Clinical Professor, University of Copenhagen.

Affects the brain

Most monkeys on Saint Kitts are wild, but some are housed in groups in research facilities, and when alcohol consumption is studied, the monkeys have to be kept under controlled conditions to be able to measure their individual alcohol intake. Alcohol-preferring monkeys were offered alcohol for 4 hours every day for a 10-day period. The monkeys were then treated with two GLP-1 analogues, exenatide (Bydureon®) or liraglutide (Victoza®) for several weeks, and at the end of the treatment period their alcohol intake was measured for 10 days.

“Although we observed the same trends with both drugs, liraglutide clearly appeared to have the greatest effect, since it reduced the monkeys’ alcohol intake by up to 30% compared with those that did not take the drug. Alcohol intake reverted to the normal level a few days after the monkeys stopped taking the drug. It is too early to conclude about any differences between the two drugs because the studies were not carried out simultaneously and because the alcohol intake differed in the studies.”

These GLP-1 analogues have had similar effects in rats and mice, but this is the first time that the effects have been studied in primates, whose physiology is more similar to that of people. Some of the monkeys in Saint Kitts even have the same natural urge to consume alcohol as some people.

“The previous studies on mice showed that GLP-1 analogues influence blood glucose in the peripheral tissue, such as by GLP-1 analogues stimulating the release of insulin in the pancreas, but GLP-1 analogues probably influence alcohol intake by affecting the brain.”

The researchers think that GLP-1 analogues affect the brain’s secretion of dopamine, which means that people do not achieve the same feeling of happiness when they drink alcohol after being treated with these drugs. In a future clinical trial, the researchers will use brain scans to examine the possible central effects of GLP-1 analogues on the brain.

“We have already started a clinical study and expect to complete it in the next year. In addition to examining how GLP-1 analogues may affect the human brain, the research will also determine whether GLP-1 analogues also reduce alcohol intake among people with alcohol use disorder or excessive alcohol consumption.”

A shorter path to treatment

These new results have wide-ranging perspectives. In Denmark alone, an estimated 160,000–180,000 people have alcohol use disorder. In addition, presumably 4–5 times as many people have excessive alcohol intake. About 20,000 people receive pharmaceutical treatment, with most taking disulfiram (Antabus®).

“The problem with Antabus® is that it does not eliminate the cause: the urge to drink alcohol. Of course, it gives people who are dependent a nasty reaction if they simultaneously drink alcohol, but the physiological craving for alcohol remains. We want to find a drug that can remove this craving.”

Some research has been conducted on drugs that can eliminate the craving for alcohol, and several drugs in addition to disulfiram are registered for treating alcohol use disorder, but new and effective drugs are still needed to target this condition.

“The major benefit of GLP-1 analogues is that they are approved for treating people with diabetes and obesity, and since they are sometimes related to excessive consumption of alcohol, there is justified hope that people with diabetes who are overweight and have alcohol problems may benefit from GLP-1 analogues. People with normal weight who do not have type 2 diabetes may also benefit from this type of medicine. Future clinical trials must decide this.”

Effects of glucagon-like peptide 1 analogs on alcohol intake in alcohol-preferring vervet monkeys” has been published in Psychopharmacology. Researchers from the Novo Nordisk Foundation Center for Basic Metabolic Research participated in the study.

Anders Fink-Jensen
Clinical professor
Alcohol use disorder is a major public health problem in large parts of the world including Europe and the USA, imposing a high cost on society and estimated to cause 6% of all deaths . Alcohol use disorder is underdiagnosed and undertreated, and more than 2/3 of patients in abstinence-oriented treatment will relapse within the first year of achieving abstinence. Currently available pharmacotherapies such as disulfiram, naltrexone, acamprosate, and nalmefene have low to moderate efficacy. Thus, there remains a strong need for new molecular targets in the medical treatment of alcohol use disorder. Glucagon-like peptide-1 (GLP-1)-based therapy has been used in the treatment of type 2 diabetes since 2006. GLP-1 is an incretin hormone secreted from endocrine L-cells of the small intestine. GLP-1 has insulinotropic effects and inhibits glucagon release, which together lower blood glucose levels (Holst 2007). GLP-1 is also produced as a neurotransmitter in the brain and acts centrally to regulate nutrient intake, and GLP-1 receptors are expressed in brain areas involved with reward and addiction, such as the ventral tegmental area and nucleus accumbens in rodents, humans, and non-human primates . The GLP-1 system has therefore attracted interest as a potential target for treating addictions, and GLP-1 receptor agonists have shown promise in reducing alcohol intake in rodents . Human gene variants of the GLP-1 receptor also show an association with the prevalence of AUD and with behavioral and neurological responses to alcohol in human laboratory studies. Endogenous GLP-1 is degraded within minutes, but GLP-1 analogs with significantly longer half-lives have been developed as diabetes medications. Here, we tested two different clinically used peptide compounds: exenatide, in an extended-release formulation, and liraglutide. Pharmacokinetic properties of the two drugs in humans are summarized in Table 1. Evidence from rodent studies indicates that both exenatide and liraglutide penetrate the brain after systemic administration. In humans, exenatide requires several weeks to reach steady blood levels, and liraglutide requires careful up-titration to reduce side effects such as nausea and vomiting.