What is GLP-1 & Does it Affect Weight & Cognition?

Choosing between GLP-1 Receptor Agonists and DPP-4 Inhibitors: A Pharmacological Perspective

What is GLP-1 & Does it Affect Weight & Cognition?

In recent years the incretin therapies have provided a new treatment option for patients with type 2 diabetes mellitus (T2DM). The incretin therapies focus on the increasing levels of the two incretin hormones, glucagon- peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP).

This results in increased glucose dependent insulin synthesis and release. GLP-1 receptor agonists such as liraglutide and exenatide exert an intrinsic biological effect on GLP-1 receptors directly stimulating the release of insulin from pancreatic beta cells.

DPP-4 inhibitors such as sitagliptin and linagliptin prevent the inactivation of endogenous GLP-1 and GIP through competitive inhibition of the DPP-4 enzyme. Both incretin therapies have good safety and tolerability profiles and interact minimally with a number of medications commonly prescribed in T2DM.

This paper focuses on the pharmacological basis by which the incretin therapies function and how this knowledge can inform and benefit clinical decisions. Each individual incretin agent has benefits and pitfalls relating to aspects such as glycaemic and nonglycaemic efficacy, safety and tolerability, ease of administration, and cost.

Overall, a personalized medicine approach has been found to be favourable, tailoring the incretin agent to benefit and suit patient's needs such as renal impairment (RI) or hepatic impairment (HI).

1. Introduction

The pathophysiology of type 2 diabetes mellitus (T2DM) is complex and involves many facets. Currently a combination of metformin and lifestyle alterations is the intervention of choice. However, due to the progressive nature of T2DM, inevitably other supplementary therapies are often needed [1].

This has led to the development and approval of the incretin-based therapies targeting the incretin system, dysregulation of which arguably plays an important role in the pathogenesis of T2DM.

The incretin system can briefly be summarised as the amplification of insulin biosynthesis and secretion due to the actions of two key hormones, glucagon peptide 1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) [2, 3].

GLP-1 and GIP are collectively known as the incretin hormones and are primarily released from the gastrointestinal tract upon ingestion of oral glucose substance [4]. In healthy individuals the insulin response to oral glucose is therefore much higher than to IV glucose, illustrating the potentiating effect of the incretin hormones.

In patients with T2DM, the insulin response to oral glucose is similar to IV glucose, providing evidence that the incretin response is lost in these individuals.

Modulation of the incretin system is therefore a viable treatment option and has had reasonable success in the form of two currently approved therapies, dipeptidyl peptidase 4 (DPP-4) inhibitors and GLP-1 receptor agonists [5]. With these new treatment options come new possibilities and options for clinicians but questions still remain, where do these new incretin therapies fit in with clinical practice and when should each therapy be prescribed? This paper aims to assess the benefits and pitfalls of each therapy from a pharmacology perspective.

2. Pharmacology of GLP-1 Receptor Agonists & DPP-4 Inhibitors

As mentioned above, the incretin hormones consist of GLP-1 and GIP, both released upon the ingestion of oral glucose substance. The relative importance of GLP-1 and GIP has been hotly debated. However, in T2DM the insulinotropic activity of GIP is negligible in contrast to GLP-1 [6]. Most attempts to modulate the incretin system are therefore directed at GLP-1.

GLP-1 is a 30 amino acid peptide hormone, secreted by L cells of the terminal ileum in response to glucose, amino acids, and fats [7]. GLP-1 stimulates glucose dependent insulin release from pancreatic beta cells and suppresses glucagon release [5]. Exogenous administration of GLP-1 has been shown to be effective in restoring the first phase insulin response.

A study in 2002 by Zander and colleagues also demonstrated that patients with T2DM administered GLP-1 exhibited decreased fasting plasma glucose (FPG) and postprandial glucose (PPG) levels [8]. However, GLP-1 has a circulating half-life of only ~1.5 mins as it is inactivated rapidly by the DPP-4 enzyme [9].

This has led to two different approaches to boosting the circulating levels of the incretin hormones. The first is distinctly pharmacological and involves creating GLP-1 mimetics which are more resistant to inactivation by DPP-4.

These GLP-1 mimetics are agonists at the GLP-1 receptor and exert intrinsic biological activity, directly stimulating the release of insulin from pancreatic beta cells [10]. The second approach involves inhibiting the DPP-4 enzyme resulting in increased physiological levels of the incretin hormones GLP-1 and GIP [5].

Currently GLP-1 agonists have a higher status in the second line treatment of T2DM as stated in the guidelines from the American Diabetes Association [11] and the American Association of Clinical Endocrinologists [12].

Two GLP-1 receptor agonists exenatide and liraglutide are currently licensed in the USA, Europe, and Japan [13], however many more are in development. Exenatide is an exendin-4 GLP-1 mimetic with ~53% homology to endogenous GLP-1, it is currently approved as a monotherapy or in combination with metformin and/or sulphonylureas [14].

Liraglutide in contrast is a GLP-1 analogue with ~97% homology to human endogenous GLP-1. The 3% difference in homology results from the addition of a C16 fatty acid side chain, prolonging half-life and enabling liraglutide to be administered as a once daily dose [13].

Liraglutide and exenatide are administered subcutaneously (SC) via pre-filled injection pens once and twice daily, respectively. An additional exenatide once weekly preparation was approved in February 2012 by the US Food and Drug Administration (FDA).

As these GLP-1 receptor agonists are able to be administered at supraphysiological doses this results in high circulating levels of GLP-1. At a pharmacological level this elicits a greater insulin response than DPP-4 inhibitors, which function only within physiological parameters [10].

The current DPP-4 inhibitors available are saxagliptin, sitagliptin, and linagliptin licensed in most of the world, additionally vildagliptin is licensed in Europe and Latin America, and alogliptin is licensed only in Japan [15–17].

DPP-4 inhibitors are competitive inhibitors of the DPP-4 transmembrane glycoprotein resulting in increased physiological levels of the incretin hormones [18]. DPP-4 inhibitors are considered second line treatments for T2DM either as a monotherapy or in combination with metformin and/or sulphonylureas [19].

One advantage of DPP-4 inhibitors lies in the fact that they are administered orally, increasing compliance. Most of the DPP-4 inhibitors available do not interfere with the cytochrome P450 (CYP) pathway with the exception of saxagliptin, metabolised by CYP 3A4 [20].

It is noteworthy that linagliptin is particularly different to the other drugs of its class as it is not extensively renally excreted and eliminated primarily via the hepatic route. This is an important development and will be discussed, as suitability for renal impairment (RI) is a desirable characteristic in any antidiabetic drug [21].

Several factors are to be considered when selecting between DPP-4 inhibitors and GLP-1 agonists for the second line treatment of patients with T2DM.

These include but are not limited to glycaemic efficacy in terms of the ability to reduce haemoglobin A1c (HbA1c), FPG, and PPG levels; nonglycaemic efficacy; mechanistic considerations; effects on pancreatic beta-cell function; safety and tolerability; ease of administration; cost [1].

4. Glycaemic Efficacy: Clinical Studies

The results of several phase 2 and 3, double-blind, randomized controlled, or active comparator trials have shown that GLP-1 receptor agonists generally produce greater reductions in HbA1c and blood glucose than DPP-4 inhibitors.

GLP-1 receptor agonists also promote significantly more weight loss than DPP-4 inhibitors which are weight neutral.

These observations have been made in most cases indirectly through systematic reviews and meta-analyses of incretin studies as very little data is available from direct comparisons [1, 10].

This section provides an overview of the limited data available on glycaemic efficacy from selected head-to-head incretin studies. Most studies relate to comparisons made between GLP-1 receptor agonists and the DPP-4 inhibitor sitagliptin, therefore only extrapolation can be made regarding other DPP-4 inhibitors.

4.1. Exenatide versus Liraglutide

A 26-week randomized, open-label, multinational, parallel group study by Buse and colleagues compared the effectiveness of exenatide with liraglutide, both GLP-1 receptor agonists [22].

A total of 389 subjects completed the initial study with 202 randomized to once daily liraglutide and 187 randomized to twice daily exenatide. Subjects were adults with inadequately controlled T2DM currently taking maximally tolerated doses of metformin, sulphonylurea, or both.

Liraglutide was administered as a once daily 1.8 mg dose and exenatide as a twice daily 10 μg dose. The primary outcome measured was change in HbA1c from baseline. Liraglutide was found to decrease HbA1c levels significantly more than exenatide, −1.12% versus −0.79%, respectively ().

In terms of clinical significance this resulted in a greater number of subjects achieving the target HbA1c of

Source: https://www.hindawi.com/journals/jnme/2012/381713/

GLP-1 Agonists: How They Help to Reduce Blood Sugar

What is GLP-1 & Does it Affect Weight & Cognition?

fertnig/istock 

GLP-1 receptor agonists are a type of non-insulin medication that is used in combination with diet and exercise to help treat type 2 diabetes.

The specific role of these drugs is to help lower blood glucose levels—specifically, hemoglobin A1C—and to aid in weight loss.

Research has shown that GLP-1 receptor agonists can have other health benefits, including positive effects on blood pressure, cholesterol levels, and beta-cell function.

These injectable drugs are prescribed along with oral diabetes medicines and insulin therapy. As such, they aren't regarded as first-line diabetes drugs, but they can be a valuable part of treatment with relatively few side effects.

GLP-1 stands for glucagon- peptide, a type of hormone known as an incretin hormone that's lower than normal in people with type 2 diabetes.

GLP-1 receptor agonists belong to a class of medications known as incretin mimetics that help the pancreas to release the optimal amount of insulin, a hormone that transports glucose (sugar) to tissues in the body where it can be used for energy.

These drugs also slow the rate at which food leaves the stomach, which helps to control post prandial (after meal) blood sugar levels.

By mimicking the following effects of GLP-1 on several parts of the body, GLP-1 receptor agonists help to control appetite and blood sugar levels:

GLP-1 sends a signal to the hypothalamus, the part of the brain responsible for appetite and thirst, to take in less water and food—an effect that can lead to weight loss.

GLP-1 stimulates gluconeogenesis—the synthesis of glucose in the body. More simply, it's the conversion of protein or fat (rather than carbohydrates) to sugar for the body to use as fuel in the muscle. An increase in this process can help to lower blood sugars by stimulating glucose uptake by the cells and increasing how efficiently the body uses insulin.

When GLP-1 comes in contact with glucose, the pancreas is triggered to secrete more insulin, thereby lowering the amount of post-meal glycogen in the blood. GLP-1 also decreases the secretion of glucagon—a hormone that helps to prevent blood sugar levels from dipping too low. In people with type 2 diabetes, glucagon can cause blood glucose levels to become too high.

GLP-1 lowers hepatic (liver) glucose output, which helps to lower blood sugars. As gluconeogenesis increases, glucagon receptors are reduced in the liver, inhibiting glucose formation and stimulating glucose uptake by cells, thus lowering the amount of glucose in the blood.

GLP-1 decreases both the secretion of acid in the stomach and how quickly food is emptied from the stomach, prolonging the sensation of fullness that in turn can limit how much a person eats and ultimately lead to weight loss.

There are two types of GLP-1 receptor agonist: short-acting formulas that typically are taken once or twice a day, and long-acting formulas, which are taken once a week. The type prescribed typically is a number of factors, including medical history, insurance coverage, and price (GLP-1 receptor agonists can be expensive), personal preference, and effectiveness of blood sugar control.

Short-acting GLP-1 Receptor Agonists
Name of drugDoseProsConsOther considerations
Byetta (exenatide)0.5 micrograms (mcg) twice daily the first month; 10 mcg twice a day thereafterRelatively inexpensive compared to newer GLP-1 agonists Must be given 60 minutes before a meal sometimes can be inconvenientBecause exenatide is excreted through the kidneys, it's  not recommended for people with GFRs of 30 or less
Victoza, Saxenda (liraglutide)0.6 mcg per day the first week; 1.2 mcg daily thereafter, increasing to 1.8 mcg per day if necessary to reach optimal blood glucose levelsProven to promote the most weight lossAssociated with a high incidence of nausea Nausea caused by liraglutide may be a contributing factor to weight loss
Adlyxin (lixisenatide)10 mcg daily the first two weeks, increasing to 20 mcg dailyn thereafterHas relatively the same efficacy as Byetta.Must be dosed daily 60 minutes before the first meal of the dayIs excreted via the kidneys; shouldnot be used by people with low GFRs 
Long-acting GLP-1 Receptor Agonists
Name of medicationDoseProsConsOther considerations
Bydureon (exenatide)2 milligrams (mg) once per weekComes in a pre-filled penIs excreted  via the kidneys and should be avoided by anyone with a GFR of 30 or lessReduces A1C by about 1.5 percent 
Trulicity (dulaglitide)0.75 mg weekly; increase to 1.5 mg after 6 to 8 weeks.Comes as a pre-filled penNot covered by all insurance providers; can be expensiveReduces A1C by about 1.4 percent
Ozempic (semaglutide)0.25 mg the first four weeks; 0.5 mg thereafter. If after 4 weeks more blood sugar control is needed, dose can be increased to 1 mg.Comes as a pre-filled penAs a newer drug, can be priceyReduces A1C by as much as 1.8 percent

All GLP-1 receptor agonist medications are injectable, meaning they're given with a syringe and needle or with a pre-filled dosing pen, depending on the drug. Both short-lasting or long-lasting GLP-1 receptor agonist shots are subcutaneous—inserted into the fatty tissue just below the surface of the skin.

If your doctor prescribes a GLP-1 receptor agonist, he or she will go over the steps for how to inject it yourself into either your abdomen or upper thigh. If you're unable to give yourself a shot, someone else can administer the drug into your upper arm.

To self-inject a GLP-1 receptor agonist medication:

  1. Examine the solution to make sure it's clear, colorless, and has no floating particles. Check the label to make sure the expiration date has not passed.
  2. Gather your supplies: an alcohol pad, bandage, gauze, or tissue, and your prepared or mixed medication in a pen or vial and syringe.
  3. Wash your hands.
  4. Use the alcohol pad to clean the area where you'll give the injection; rotate injection sites so that you aren't sticking the same area over and over.
  5. Draw up your correct dose, either in the prefilled pen or syringe.
  6. Take a large pinch of skin and pull it away from the muscle underneath.
  7. Holding the pen or syringe a dart, quickly insert the needle at a 90-degree angle to the skin.
  8. Slowly inject the medication.
  9. Release the skin, then withdraw the needle.
  10. Apply bandage, gauze, or tissue as necessary.

Never reuse or share supplies. You should draw up your medication into a fresh syringe every time you self-inject. Most pens should be discarded after 30 days, even if there is some solution left inside.

Overall, GLP-1 receptor agonists are safe and cause few side effects.

These include nausea, vomiting, and diarrhea, which affect 10 percent to 40 percent of people who take a GLP-1 receptor agonist. They are most ly to occur with short-acting medications and tend to be less severe the longer a person takes the medication.

Other potential side effects of GLP-1 receptor agonists include constipation, bloating, indigestion, and headache. There also can be some redness, itching, or soreness of the skin at the injection site.

Although rare, these side effects should be treated as an emergency:

  • ongoing pain in the upper left or middle of the stomach that may spread to the back, with or without vomiting
  • a skin rash or hives
  • itching
  • pounding heart
  • dizziness or fainting
  • swelling of the eyes, face, mouth, tongue, throat, feet, ankles, or lower legs
  • trouble swallowing or breathing
  • hoarseness
  • decreased urination
  • very dry mouth or skin
  • extreme thirst

In animal studies, both liraglutide and dulaglutide have been shown to promote thyroid cell tumors. Although these drugs haven't been evaluated in humans for this potential complication, it is recommended that people with a history of or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 do not use GLP-1 receptor agonists.

With certain GLP-1 receptor agonists, there is a possible small increased risk of pancreatitis (inflammation of the pancreas).

This medication is not recommended for people who:

  • Have a history of pancreatitis
  • Have a history of gastroparesis (paralysis of the stomach)
  • Have medullary thyroid cancer or multiple endocrine neoplasia type 2 or a family history of these conditions
  • Are on dialysis (as the safety of using GLP-1 agonists in this situation hasn't been proven)

In addition, people with impaired kidney function due to diabetes who have a GFR (glomerular filtration rate) of 30 or less should not use Bydureon or Byetta but may be able to take another GLP-1 receptor agonist.

Effective treatment for type 2 diabetes is a subject of robust research. There is a great deal of interest in developing better and better medications, including safer, more convenient, and more effective GLP-1 receptor agonists.

In fact, one such option, an oral form of semaglutide, is being considered for approval by the U.S. Food and Drug Administration.

Not only does this version of the drug help control blood sugar levels, but it has also been shown to reduce heart risks—a bonus benefit of a drug that may one day be taken as a pill rather than with a needle.

Source: https://www.verywellhealth.com/glp1-receptor-agonists-4134034

What is GLP-1 & Does it Affect Weight & Cognition? | Nature Knows

What is GLP-1 & Does it Affect Weight & Cognition?

Scientists think that glucagon- peptide 1 (GLP-1) helps the body release insulin and keep blood sugar in check. Discover the science behind this hormone and whether certain natural factors can increase it.

Disclaimer: The aim of this post is to describe the scientific findings related to GLP-1. It includes some information about the clinical use of GLP-1 agonists as anti-diabetic medications. Please discuss your medications and symptoms with your doctor. What is GLP-1?

Researchers describe Glucagon- Peptide-1 (GLP-1) as both a neuropeptide and an incretin [ 1 ].

A neuropeptide is a peptide compound that has an effect on the nervous system. An incretin is a metabolic hormone that reduces glucose levels in the blood after meals.

Note that GLP-1 is not the only hormone that affects blood sugar regulation and insulin production.

Many other important enzymes DPP-4, hormones – such as glucagon, growth hormone, epinephrine, cortisol, sex hormones, and thyroid hormones – and other pathways also impact blood sugar and insulin balance.

Plus, blood sugar control can involve many other possible factors – including blood chemistry, environment, health status, and genetics – that may vary from one person to another.

GLP-1 has received widespread scientific attention due to its involvement in insulin and blood sugar control. That’s how a new class of medications was born, which are called GLP-1 agonists. These medications are typically given as injections (with the exception of semaglutide) [ 1 ].

Doctors may prescribe GLP-1 agonists to people with type 2 diabetes who have poor blood sugar control and are taking anti-diabetic therapy by mouth.

Approved GLP-1 agonists include: Byetta/Bydureon (exenatide)

Victoza (liraglutide)

Lyxumia/Adlyxin (lixisenatide)

Tanzeum (albiglutide)

Trulicity (dulaglutide)

Ozempic (semaglutide injections)

Rybelsus (oral semaglutide – the only oral GLP-1 agonist)

Side effects of GLP-1 agonists include weight loss and nausea [ 2 ].

GLP-1 agonists have been associated with asymptomatic pancreatitis and pancreatic cancer in limited studies, but this association is still being studied [ 3 ].

DPP-4 inhibitors are another class of anti-diabetic drugs. They reduce the activity of an enzyme called DPP-4, which deactivates GLP-1 and another incretin called insulinotropic polypeptide (GIP). Both GLP-1 and GIP are released after meals to reduce blood sugar [ 4 ].

Thus, these drugs support glucose balance and GLP-1 activity in the body. DPP-4 inhibitors include:

If you have diabetes, your doctor will discuss your medication options with you in detail, including the potential use of GLP-1 agonists or DPP-4 inhibitors. GLP-1 Research & Proposed Health Effects

Blood Glucose & Diabetes

As mentioned, substances that act similar to GLP agonists – so-called GLP-1 agonists – are used as anti-diabetic medications.

GLP-1 increases insulin and decreases glucagon levels, which will result in decreased blood glucose [ 8 , 9 ].

GLP-1 seems to delay stomach emptying, which slows down glucose spikes and makes it easier for the body to maintain blood sugar levels right after a meal [ 10 ].

In animals with diabetes, GLP-1 agonists improve the function of insulin-producing beta cells in the pancreas. Scientists think that these drugs have the potential to regenerate pancreatic cells, but this hasn’t been proven in humans [ 11 , 12 ].

Cell-based research is investigating whether fat muscle cells also increase glucose uptake when GLP-1 is higher [ 13 ].Before GLP-1 agonists were discovered, scientists explored the effects of unchanged GLP-1 injections in diabetics [ 14 ].

In one study, 6-weeks long administration of GLP-1 to type 2 diabetic patients reduced fasting blood glucose and hemoglobin A1c, a measure of long-term sugar control ( 15 ).However, GLP-1 has a very short half-life of about 1.5 minutes and is rapidly suppressed by an enzyme called dipeptidyl peptidase-4 (DPP-4).

GLP-1 agonists were developed to overcome these issues and achieve long-term sugar control [ 16 , 14 ]. Appetite & Weight Control Some scientists hypothesize that GLP-1 decreases appetite by acting on specific areas in the brain. One side effect of GLP-1 agonists is weight loss, which is usually desired in patients with type 2 diabetes.

However, GLP-1’s effects on weight haven’t been properly verified in humans without diabetes [ 1 ].In fasted rats, GLP-1 appeared to produce a feeling of satiety. The authors posited that GLP-1 in the hypothalamus reduces food intake [ 17 ].One animal experiment used chocolate milk to tempt animals.

They suggested that GLP-1 reduces the excitement of eating food–called the anticipatory food reward , which may result in a decrease in appetite and motivation toward food [ 18 ]. GLP-1 in mentioned in our post about hormones implicated in weight control .

We can’t apply animal findings to humans, so we have yet to see if this hormone really reduces appetite and weight in people who struggle with obesity.Many substances that are initially claimed to cause weight loss in animals fail further clinical research.Let’s remember leptin was initially called an “obesity wonder drug” animal experiments.

Well, it turned out that leptin actually better fits the nickname “fat hormone” and we’re still in the dark as to what it exactly does in the human body. GLP-1 obesity research might face a similar fate. Brain & Mental Health A study on rats suggested that GLP-1R in the hippocampus enhanced learning and memory.

According to one unproven hypothesis, GLP-1 might be involved in protecting the brain from seizures and neuronal damage. If proven true, this would add to our knowledge about the gut-brain connection [ 19 ].A GLP-1 agonist and anti-diabetic drug, exenatide, is also being researched in neurogenerative disorders.

Given to 45 patients with Parkinson’s disease, exenatide seemed to improve motor and cognitive symptoms compared to the control. Side effects were weight loss and nausea. Large-scale studies are needed [ 2 ].Some scientists have proposed that the potentially protective properties of GLP-1 agonists should also be researched in Alzheimer’s disease [ 20 ].In lab animals, GLP-1 seems to improve mood and anxiety. It is hypothesized to activate orexin , which increases wakefulness . However, the impact of GLP-1 on mood and wakefulness in humans is unknown [ 21 ]. Other Research Areas Scientists are investigating […]

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Source: https://www.natureknowsproducts.com/what-is-glp-1-does-it-affect-weight-cognition/

Beneficial Effects of GLP-1 Agonist in a Male With Compulsive Food-Related Behavior Associated With Autism

What is GLP-1 & Does it Affect Weight & Cognition?

Restricted and repetitive thoughts and behaviors (RRBs) appearing inappropriate to the situation and odd in context represent some of the core diagnostic features in autism spectrum disorder (ASD) and associate with difficulties in interpreting everyday social signals and limited language and cognitive capabilities in ASD individuals (1). These are analogous to compulsions, which are driven by repetitive urge to perform the behavior and the tendency to repeat repetitive actions in a stereotyped or habitual manner (2). Voluntary control of compulsions is limited and the ability to delay or inhibit behaviors is diminished. Compulsions can significantly disturb the daily life and provoke far-reaching behavioral and functional problems. Obsessive compulsive disorder (OCD) is characterized by compulsions and/or obsessions that cause functional impairment (3). Rewarding effects followed by reduced anxiety caused by obsession link compulsion in OCD to behavioral addiction.

Differentiating RRBs of ASD from the obsessions and compulsions in OCD is challenging because of the heterogeneity of symptom manifestation and remarkable comorbidity characterizing both disorders.

Particularly high-functioning persons with ASD have an elevated risk for OCD and co-occuring substance abuse (4). The high comorbidity and shared familial risks suggest that ASD and OCD-spectrum disorders have partially overlapping etiological mechanisms (5).

Both ASD and OCD involve behavioral symptoms combined with cognitive manifestations (obsessions in OCD and insistence on sameness and preoccupations in ASD), which are presumed to be underpinned by anxiety, compromised executive functioning, and sensory phenomena.

However, un in OCD, these behaviors often appear pleasurable and self-soothing in ASD, and the individuals may even behave aggressively if they are obstructed while performing the activities (5).

Cognitive behavioral therapy and serotonin uptake inhibitors (SRIs) are the first-line treatment for OCD (6). In the realm of pharmacological treatments for OCD symptoms in ASD, selective serotonin uptake inhibitors (SSRIs) have been reported to be beneficial (7).

However, there is some evidence that individuals with ASD appear to be particularly sensitive to behavioral activation side effects of SSRIs (6).

Antipsychotics provide therapeutic benefit for a subgroup of ASD individuals (8) but antipsychotic drugs also are disadvantaged by many side effects, including increased appetite, weight gain, and a subsequent increase in body mass index.

Since treatment resistance OCD symptoms are common, several other treatment strategies have been tested. Abnormalities identified in glutamatergic neurotransmission in OCD have led to clinical trials with “glutamate-modulating” drugs (9).

In this line of studies anti-convulsive drugs (topiramate and lamotrigine), D-cycloserine, memantine, minocycline, modafinil, N-acetylcysteine, and riluzole have been associated with beneficial therapeutic effects in OCD but their clinical utility has not been proven in relatively few studies with partially inconsistent results.

Food-related obsessions and compulsive overeating represent some of the landmark characteristics of Prader Willi syndrome (PWS). Preliminary evidence indicates that glucagon- peptide-1 (GLP-1) receptor agonists could be used to treat defects of satiety responses in this genetically based intellectual disability syndrome (10–12).

Similarly to PWS, both children and adults with ASD suffer more frequently from obesity than the general population. Here we report beneficial effects of liraglutide, a human GLP-1 analog, on food-related obsessions and compulsive eating in a case with a neurodevelopmental disorder characterized by autistic features.

No adverse side effects of liraglutide were observed in our study/patient case.

Case Report

A 20-year-old Finnish male patient is the second-born child of healthy, non-consanguineous parents with an unremarkable family history. His close relatives had no manifestations of thyroid or heritable endocrine diseases. The perinatal period was uneventful, however, deficits in eye contact behavior were noted from early infancy onwards.

By the preschool age, he demonstrated behavioral difficulties resembling those associated with autism, including perseveration and impairments in social interactive behavior including avoidance of strangers. Abnormal responses to auditory, olfactory, and oral sensory stimuli were noted.

Motor and phonic tics as well as obsessions appeared in adolescence being periodically severe.

At the age of 6;9 years, the patient received the diagnoses of pervasive developmental disorder-not otherwise specified and mild intellectual impairment, with these later, at the age of 11;2 years, having been modified to infantile autism and moderate intellectual impairment.

Behavioral problems included aggressive behavior, which resulted in treatment with risperidone being initiated at the age of 12 years. Initially the antipsychotic slightly appeared to reduce behavioral difficulties while at the same time resulting in rapid weight gain and nightmares. Within 6 months, risperidone was substituted with aripiprazole.

Aripiprazole caused initially fatigue, muscular spasms of jaw, and slurring of speech at the dose of 5 mg/day. After a break for several months, aripiprazole treatment was continued and the dose was slowly increased to 7.5 mg/day.

Agitation and disturbing daily RRBs such as switching on and off a water tap, checking, and jumping led to the combining of citalopram to the medication at the age of 14;10 years. Nevertheless, the gradually increased dose of citalopram to 20 mg/day did not improve the situation and especially food-related obsessions and constant weight gain appeared problematic. Craving of food, particularly sweet drinks, led the patient to e.g., steal food. A temporary increase in alanine transferase (ALT; 77 U/L, reference range

Source: https://www.frontiersin.org/articles/439148

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