Anti-Consumption Agents: Tirzepatide and Semaglutide for Treating Obesity-Related Diseases and Addictions, and Improving Life Expectancy

Abstract

American culture encourages overconsumption, fueled by ubiquitous availability and pervasive marketing of ultra-processed foods and other addictive substances. This chronic overindulgence has contributed to rising rates of obesity, type 2 diabetes (T2D), substance abuse, mental health disorders and premature mortality. Glucose-like peptide-1 agonists (GLP-1RAs) affect the brain’s reward pathway that mediates addiction to foods and various other substances. Evolving data suggest that tirzepatide and semaglutide may be the first effective “anti-consumption” agents with potential applications in reducing food cravings, obesity, alcohol consumption, nicotine addiction, recreational drug use, and even uncontrollable shopping behaviors. Tirzepatide and semaglutide, unlike prior weight-loss drugs, are effective and relatively safe/well-tolerated medications that are associated with reduced risks for myocardial infarction, stroke, cardiovascular death, heart failure, progressive kidney and liver disease, obstructive sleep apnea, debilitating osteoarthritis, polycystic ovarian syndrome, neurodegenerative disease and premature mortality. Observational studies show that GLP-1RAs are associated with spontaneous nonvolitional reductions in use of alcohol, nicotine, and recreational drugs. Because obesity and substance abuse are so prevalent in the United States, GLP-1RA drugs may be uniquely helpful in addressing overconsumption and addiction issues thereby improving overall health and life expectancy.

Introduction

We can do what we want, but we cannot choose what to want, desire and crave. In this sense, we are not free.

Arthur Schopenhauer presented this idea in The World As Will, a book initially published in 1818. Now, two centuries later, an emerging drug class may have the power to liberate people from some self-destructive habits. Glucagon-like peptide 1 agonists (GLP-1RA), specifically tirzepatide and semaglutide, appear to quiet cravings for hyperpalatable foods, alcohol, tobacco, and recreational drugs.

America has become a culture that encourages overconsumption, fueled by the ubiquitous availability and pervasive marketing of ultra-processed foods and other addictive substances.^1–3 This chronic overindulgence comes at a steep cost, contributing to our rising rates of obesity, type 2 diabetes (T2D), substance abuse, mental health disorders and premature mortality.^4–11

The obesity rate has more than tripled and now ~73% of United States (US) adults are classified as overweight or obese.^12–18 In the 20^th century life expectancy rose from 47 years to nearly 80 years due to antibiotics, public sanitation, vaccines, and drugs for treating/preventing cardiovascular disease (CVD) and other illnesses.^{19, 20} However, the obesity epidemic that began 40 years ago eroded these gains, and by 2014, life expectancy started falling in the US, a trend that the COVID pandemic exacerbated.^{21, 22} Consequently, over the last 4 decades the average lifespan in the US has fallen off compared to nations such as Switzerland, Sweden, Germany, Italy, Japan, and Australia who are quite similar to us except for their much lower rates of obesity and substance abuse (Fig. 1).²³

Figure 1.

US has been lagging similar countries in life expectancy since 1980.²³ Permission: Content on this site is licensed under a Creative Commons Attribution/Non-Commercial/No Derivatives 3.0 United States license, which may be accessed here http://creativecommons.org/licenses/by-nc-nd/3.0/us/deed.en_US. We reserve the right to change our permitted uses at any time and will provide users with updated information on our site if such permitted uses change.

Obesity is not the only epidemic causing a decline in life expectancy in the US. Recreational drug overdoses, alcohol-related deaths and suicides have risen sharply since 2014.^{21, 24–26} Princeton economists Angus Deaton and Anne Case refer to these as “deaths of despair”.²⁵ Across the globe, the US has the highest per capita consumption of recreational drugs, and our drug use disorder death rate is 19 per 100,000 people–more than twice as high as the next highest nation. The US death rate due to opioids alone was 15/100,000 people.²⁴ The US also has the highest death rates from cocaine and methamphetamine and leads the world in drug-related disability-adjusted life years (DALYs) lost, which represents the number of healthy years of life lost due to the use of recreational drugs averaged across a nation’s entire population. Americans suffered 6.7 DALYs lost per capita.²⁴

Alcohol abuse has also been rising in the US population: from 1999 to 2020 alcohol-related deaths doubled, with increases in both sexes and across all age groups.²⁷ Alcohol-related deaths in the US increased from 38/100,000 in 2016 to 48/100,000 in 2021.²⁸ Moreover, the US is among top nations in per capita online shopping and gambling.^29–31

Until now, physicians focused on preventing noncommunicable disease and improving life expectancy have been frustrated by not being able to reliably solve weight problems and substance abuse issues for many of their patients. Evolving data suggest that GLP-1RAs may be the first effective “anti-consumption” agents with potential applications in reducing food cravings, alcohol consumption, nicotine addiction, recreational drug use, compulsive gambling, and even uncontrollable shopping behaviors.^32–34 Because obesity and substance abuse are so prevalent, GLP-1RA drugs are poised to be groundbreaking therapies for dealing with overconsumption and addiction issues (Central Illustration).

Central Illustration:

Tirzepatide and Semaglutide alter the reward pathway to reduce cravings, over consumption, which improves health and longevity.

Tellingly, for the first time in 40 years obesity rates declined last year in the US. Increased use of tirzepatide and semaglutide is likely the principal reason for this reversal (Fig. 2).³⁵ Already 1 in 8 US adults has been prescribed a GLP-1RA, and the drop in obesity is steepest among college graduates—the demographic most likely to be on these drugs.³⁵ Eric Topol, MD, a cardiologist who leads Scripps Research in San Diego, California, called GLP-1 drugs “the most important drug-class breakthrough in medical history”.³⁶

Figure 2.

Obesity rate (%) from 1980 to 2023 among US adults ≥20 years of age.³⁵ Requested permission from Financial Times, London.

Mechanisms of Action for GLP-1RA

GLP-1RA drugs mimic the action of a natural incretin hormone, glucagon-like peptide-1, which is secreted by the intestines in response to nutrient intake. These drugs exert their effects in several tissues, including the pancreas, gastrointestinal tract, and central nervous system.³⁷ Tirzepatide and semaglutide are both GLP-1 receptor agonists, but tirzepatide also stimulates gastric inhibitory polypeptide (GIP) receptors, making it a dual agonist.³⁸ These agents slow gastric emptying, which prolongs the feeling of fullness after eating and reduces the frequency of hunger pangs, contributing to decreased caloric intake.^{37, 38} GLP-1RAs also favor the utilization of stored fat as an energy source and reduce proinflammatory visceral fat more significantly than subcutaneous fat.³⁷

GLP-1 receptor activation in the hypothalamus and brainstem reduces appetite and enhances satiety. Critically, GLP-1RA agonists also affect the mesolimbic pathway, particularly the nucleus accumbens (NAc) and the ventral tegmental Area (VTA). These regions are crucial components of the reward pathway that appears to mediate addiction to foods and various other substances including alcohol, opioids, nicotine, cocaine, etc.^39–41 Semaglutide and tirzepatide seem to uniquely modulate GABA release in the central amygdala and infralimbic cortex. By modulating dopamine signaling, the potent GLP1-A drugs reduce cravings and allow the individual to be more rational when faced with tempting pleasurable options/stimuli (Fig. 3).⁴⁰

Figure 3.

Brain regions important for the interaction between the GLP-1 pathway and addiction processes. GLP-1RAs attenuate behaviors relating to reward and intake of alcohol, nicotine, cocaine, and oxycodone. Nucleus tractus solitarii (NTS) of the brain stem, ventral tegmental area (VTA), nucleus accumbens (NAc) shell, laterodorsal tegmental area (LDTg), basolateral amygdala (BLA), lateral septum (LS) and hippocampus (HIP), paraventricular nucleus (PVN), arcuate nucleus (ARC) and lateral hypothalamus (LH) and interpeduncular nucleus (IPN). The ↓ symbol indicates an attenuation of cravings/behaviors and Ø reflects no change.⁴⁰ Figure self-made based on their information.

GLP-1RA: Effects of Obesity and Related Health Issues:

Tirzepatide and semaglutide, unlike prior weight-loss drugs, are effective and relatively safe/well-tolerated medications that improve nearly all the negative health consequences of obesity. These agents have been associated with reduced risks for myocardial infarction (MI), stroke, CVD death, heart failure (HF), kidney failure, liver disease, obstructive sleep apnea (OSA), debilitating arthritis, polycystic ovarian syndrome (PCOS), neurodegenerative disease and premature mortality.

Improved Life Expectancy

Tirzepatide and semaglutide have consistently reduced risk for all-cause mortality in large, randomized placebo-controlled trials (RCT) and meta-analyses.^42–45 The SELECT study included 17,604 overweight or obese patients with preexisting CVD but without T2D.⁴⁶ Subcutaneous semaglutide 2.4 mg/week reduced all-cause mortality by 19% during this 40-month RCT (Fig. 4). Because the curves continued to separate throughout the study, longer durations of treatment might be expected to magnify the risk reduction in all-cause mortality. The gold standard for clinical evidence—meta-analyses of large RCTs—confirms that these drugs, particularly tirzepatide and semaglutide, produce significant reductions in all-cause mortality in a variety of patient populations.^42–45

Figure 4.

All-cause mortality in the SELECT trial.⁴⁶ Permission from Elsevier granted.

Weight and Food Cravings

Both semaglutide and tirzepatide have been shown to decrease frequency and severity of food cravings,^47–49 likely mediated through subtle dopaminergic modulation.⁵⁰ Semaglutide (Ozempic for T2D or Wegovy for obesity) results in weight reduction of up to 16% of total body weight.^51–53 Tirzepatide (Mounjaro for T2D or Zepbound for obesity), has demonstrated even greater weight loss, with body weight reductions of up to 24% (Fig. 5).^{51, 54} In late-stage development are even more potent GLP-1RA drugs like retatrutide–a “triple G” agonist because it targets not only GLP-1 and GIP hormone receptors, but also glucagon receptors–which promotes increased energy expenditure. Notably, retatrutide lowers body weight by up to 26%.⁵⁵ These more potent drugs that work through the glucagon family of hormones will likely render bariatric surgeries such as gastric bypass unnecessary for everyone except those with extreme obesity and/or those who cannot afford or tolerate a GLP-1RA drug.

Figure 5.

Changes in body weight compared to placebo throughout the study, including the washout phase, which began at week 176 when tirzepatide was stopped.⁵⁴ Permission obtained.

The SURMOUNT-1 trial randomized 2500 obese prediabetics to tirzepatide or placebo.⁵⁴ The group on tirzepatide had an average weight loss of 20% bodyweight, which was sustained over the 3-years. Compared to placebo, tirzepatide prevented 94% of new cases of T2D (Fig. 6).

Figure 6.

Kaplan-Meier curves showing percentage of patients who developed T2D during the SURMOUNT-1 study.⁵⁴ Permission obtained.

MI, Stroke and CVD Death

Consistent results from large RCTs indicate that GLP-1RAs reduce risk of major adverse CVD events (MACE) defined as MI, stroke or CVD death in patients with diabetes and/or obesity.^{51, 56–60} A recent meta-analysis comprised 24 RCTs that tested GLP-1RA drugs semaglutide, liraglutiude, and dulaglutide for preventing MACE in diabetics and non-diabetics.⁴² In this meta-analysis that included 94,547 patients, GLP-1 receptor agonists compared to placebo significantly reduced risk of all-cause mortality, MI, CVD death, stroke and HF hospitalization. Both the obesity and diabetes subgroups showed reductions in MACE and all-cause mortality. These benefits are likely mediated by a combination of weight loss, reduced blood pressure, cholesterol and blood glucose levels, better sleep, more exercise, less inflammation, and improved blood vessel health.^{42, 61, 62}

In the SUMMIT study, an RCT of 731 patients with obesity and HFpEF, tirzepatide produced substantial improvements in CVD risk factors including systolic blood pressure and high-sensitivity C-reactive protein (hsCRP) (Figs. 7a and 7b).⁶³

Figure 7.

a. Changes in hsCRP levels with tirzepatide versus placebo.⁶³ Permission granted. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.

b. Changes from baseline in systolic BP (SBP) with tirzepatide versus placebo (error bars represent the standard error of the mean).⁶³ Same as above on 7a

Heart Failure

HF is the most frequent cause of hospitalization for people >65 years of age.⁶⁴ Obesity is the primary driver of HF with preserved ejection fraction (HFpEF), which is the most common type of HF in the US.⁶⁵ Multiple RCTs show that semaglutide and tirzepatide improve symptoms of HFpEF more dramatically than any prior therapy.^65–67 In the 2-year SUMMIT study, a large RCT of patients with obesity and HFpEF, tirzepatide cut the risk of CV mortality and worsening HF by 38%.⁶⁷ In that trial, tirzepatide reduced hospitalization for HF by 56% compared to placebo (Fig. 8). In SUMMIT, tirzepatide significantly regressed left ventricular hypertrophy and paracardiac adipose tissue in proportion to the weight loss induced by the drug.⁶⁶

Figure 8.

Death from CV Causes or Worsening Heart-Failure.⁶⁷ Permission obtained.

Kidney Protection

GLP-1RAs have shown strong protective effects against kidney failure. The FLOW study was a RCT testing semaglutide in 3533 patients with T2D and chronic kidney disease. Semaglutide reduced the risk of major kidney disease events by 24%, and significantly reduced individual endpoints including kidney failure, need for dialysis, death due to CVD, and all-cause mortality.⁶⁰

Tirzepatide has also shown impressive benefits for preserving kidney function. A meta-analysis reported that tirzepatide significantly improved the urine albumin-to-creatinine ratio (UACR) compared to controls, with a mean difference of −27%.⁶⁸ In the SURPASS-4 trial, tirzepatide compared to insulin glargine slowed the decline of estimated glomerular filtration rate by 2.2 mL/min/1.73 m² per year.^{60, 68, 69}

Liver Benefits

Metabolic dysfunction-associated steatotic liver disease (MASLD) is caused by excess hepatic fat deposits. MASLD affects about 1 in 4 US adults and is the leading cause of cirrhosis and liver failure. GLP-1RAs are the most effective therapy ever for reducing liver fat content, lowering liver inflammation, and improving hepatic function.^70–72 In a recent RCT, retatrutide, a potent GLP-1RA agonist in late-stage development, eliminated 86% of fat from the liver in patients with MASLD (Fig. 9). It also reduced hepatic inflammation and fibrosis.⁷³

Figure 9.

Change in relative liver fat over 48-week study in patients on placebo (PBO) versus varying doses retatrutide (RETA). P-value < 0.001 indicated by ***.⁷³ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third-party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.

Impact on Sleep Apnea

OSA is another condition closely associated with obesity. Patients treated with tirzepatide or semaglutide have reported improvements in OSA symptoms, which are likely related to the substantial weight loss observed with these agents. The SURMOUNT study was a RCT that randomized patients with OSA to tirzepatide or placebo; after 1 year the group on the GLP-1RA lost 20% of their body weight and had a 60% reduction in number of apneic episodes during sleep.⁷⁴

Brain Health

Recent studies suggest GLP-1RA drugs reduce neuroinflammation and improve brain insulin sensitivity. In large epidemiological studies, GLP-1RA drugs are associated with reduced risks for developing Alzheimer’s and Parkinson’s disease.⁷⁵ Patients treated with GLP-1RA agonists have reported improvements in mood and reductions in depressive symptoms, suggesting a potential role for these drugs in managing depression and improving long-term mental health.

Preclinical studies have demonstrated that GLP-1 receptor activation enhances neurogenesis and neuronal survival, reduces oxidative stress, improves insulin sensitivity in the brain and inhibits neuroinflammation—key factors implicated in neurodegeneration.^{76, 77} Small-scale clinical studies have shown that patients treated with GLP-1 receptor agonists exhibit improved cognitive function and reduced markers of neurodegeneration, such as amyloid-beta deposition and tau phosphorylation.⁷⁶ While larger, long-term studies are necessary to confirm these findings, the existing evidence suggests that GLP-1RAs may be promising therapies for addressing the metabolic and inflammatory underpinnings of neurodegenerative disorders.

Arthritis

A recent RCT found that overweight/obese people, who lost on average 14% of their body weight while on semaglutide, experienced major improvements in osteoarthritic knee pain.⁷⁸ Compared to placebo, the GLP-1RA drug produced dramatic pain relief, which was larger than any nonsurgical treatments previously tested in RCTs. The improvement in arthritic pain with tirzepatide and semaglutide presumably is mostly due to weight loss but these drugs also have an anti-inflammatory effect that is independent of their ability to reduce excess adipose tissue. Among people who are considering a joint replacement, semaglutide or tirzepatide could help them attain a safer weight prior to surgery, or even relieve pain enough to delay surgery for a few years or negate the need for it all together.⁷⁹

Libido Issues and Infertility

While some people report that these drugs dampen their libido, many overweight or obese people find that when GLP-1RAs help them shed their excess pounds, their self-esteem, physical vitality, and energy levels improve—all of which tend to promote a more active sex life. Notably, GLP-1RAs have not uncommonly resulted in pregnancies among women who were previously infertile. Studies show that GLP-1RAs promote fertility by increasing pre-ovulatory luteinizing peak, which boosts estrogen levels and helps to restore normal menstrual cycles.⁸⁰ This is particularly common among women with PCOS, many of whom start ovulating again after losing substantial amounts of excess visceral fat while on tirzepatide or semaglutide.⁸⁰

Effects of GLP1-A on Addictions

Anecdotal reports of GLP-1RAs reducing addictive behaviors have been posted on social media platforms increasingly over the past 2 years.³² Both in terms of observational data and neurological plausibility, tirzepatide and semaglutide appear to be promising for reducing cravings, moderating use of various substances, and treating or preventing addictions.³⁹

Alcohol

Obesity and alcohol use disorder (AUD) are frequently comorbid conditions that are likely genetically linked.⁸¹ GLP-1 activity as well as specific gene variants have been mechanistically linked to AUD and the severity of alcohol use.^{82, 83} Preclinical animal studies have shown GLP-1RA therapy decreases alcohol intake and binge drinking as well as the neurodegenerative effects of alcohol in alcohol-dependent monkeys and mice.^84–87

Patients who are prescribed tirzepatide or semaglutide for T2D and/or for weight management often report a reduced desire for alcohol, so that they find themselves unintentionally drinking less. Early clinical studies have supported these findings, showing that patients treated with GLP-1RAs report reduced craving for and consumption of alcoholic drinks. Nonvolitional >50% reductions in number of alcohol drinks/day and binge drinking episodes were noted in obese patients after they were started on semaglutide or tirzepatide, with improvements in AUD scores (Fig. 10).⁸⁸ In contrast, obese individuals after gastric bypass bariatric surgery are at increased risk of developing AUD.⁸⁹

Figure 10.

From before (a) to after (b) starting tirzepatide or semaglutide, significant reductions in drinks/day were seen. Solid circles represent means and the brackets represent standard error of means. Changes from a to b in both were statistically significant (P<0.001).⁸⁸ Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.

Opioids

In the first RCT to test these drugs against opioid addiction, patients assigned to liraglutide reported a 40% reduction in opioid cravings over the 3-week study, even though they used the lowest dose of a weak GLP-1RA and over half of the study patients dropped out before the brief study was completed.⁹⁰

An observational study of 33,000 diabetic patients found that compared to other antidiabetic medications, semaglutide was associated with an ~50% lower risk of opioid overdose during a 1-year follow-up period.⁹¹ Similarly, an observational study of 1.3 million patients with opioid use disorder or AUD reported that those who were started on a GLP-1RA had a 40% lower rate of opioid overdose and 50% lower rate of alcohol intoxication compared to those who were not started on a GLP-1RA.⁹²

Nicotine

In animal models, mice who had their GLP-1 receptor gene removed, were found to over consume nicotine compared to wild type mice and prevent overeating and weight gain during nicotine withdrawal.^{93, 94} An observational study of 222, 942 new users of diabetes medications found that semaglutide was associated with a 32% lower risk for medical encounters for tobacco use disorder compared to insulin use. People on semaglutide required fewer smoking cessation medication prescriptions and had less tobacco cessation counseling.⁹⁵ Academic studies of social media posts report that smokers commonly cut back or quit smoking after starting tirzepatide or semaglutide.^{32, 96}

Cannabis

Marijuana is the most frequently used recreational drug in the US, with 45 million regular users, one-third of whom suffer from a cannabis use disorder—defined as clinically significant impairment or distress from chronically using THC, the active ingredient of marijuana. A recent observational study based on almost 700,000 individuals found that people after being started on semaglutide were ~40% less likely to be diagnosed with cannabis use disorder.⁹⁷ These findings are particularly promising because we currently lack highly effective pharmacological treatments for all the various substance use disorders.

Compulsive Gambling, Compulsive Shopping

GLP-1RAs may curb various forms of obsessive consumption such as compulsive shopping or gambling, which like overeating or substance abuse, can be driven by dysfunction in the reward pathway. Social media is rife with anecdotes about tirzepatide and semaglutide as anti-consumption drugs affecting behaviors such as shopping and gambling further highlighting GLP-1RAs’ nascent potential for treating these issues.^{32, 96, 98}

Cocaine

Based on animal model data, GLP-1 receptor activation has been shown to attenuate cocaine seeking in animal models.⁹⁷ This provides further evidence that GLP-1 receptor agonists may be useful therapies for individuals with cocaine addiction.⁹⁹

Issues/Limitations of GLP-1RA

Tirzepatide or semaglutide when used for treatment of obesity is associated with loss of 10% of muscle mass during the 68- to 72-week interventions, which can be mitigated with increased intake of dietary protein and resistance training.¹⁰⁰ People often experience gastrointestinal side effects such as nausea, diarrhea or constipation when initiating or uptitrating a GLP-1RA. These are generally transient and tend to be mild to moderate in severity, yet lead to drug discontinuation in 3 to 6% of patients.¹⁰¹ Both tirzepatide and semaglutide have a boxed warning about a potential risk of thyroid C-cell tumors based on preclinical animal studies. However, no signal for increased risk of thyroid cancer or any other type of cancer has been seen in humans.^{102, 103}

A major practical limitation of GLP-1RA therapy is their expense, and insurance plans often do not cover GLP-RA treatment for obesity. Thus, use of tirzepatide and semaglutide for weight reduction has been skewed towards higher socioeconomic subgroups, even though obesity is more common among lower socioeconomic subgroups.³⁶ Because branded tirzepatide and semaglutide are often unaffordable, many people obtain these drugs through compounding pharmacies or illegally without a prescription from online sites. Semaglutide and tirzepatide obtained from these sources carry risks of unreliable/often inadequate dosages, harmful additives and contamination; indeed, counterfeit GLP-1RA drugs have been reported to cause serious adverse events including hospitalizations and deaths.¹⁰⁴

Conclusion:

Tirzepatide and semaglutide influence the dopamine-mediated reward pathways in the mesolimbic system, which reduces cravings. These GLP-1RAs are transformative tools for treating obesity and a host of maladies related to excessive visceral fat. By addressing multiple risk factors and comorbidities in patients with obesity/overweight and/or T2D, these agents have the potential to significantly improve life expectancy and reduce risks for MI, stroke, HF, progressive kidney and liver disease, OSA, neurodegenerative diseases and disabling osteoarthritis.

GLP-1RAs may also turn out to be uniquely effective for addressing other forms of excessive consumption or addiction. By targeting the neural circuits involved in reward and satiety, these agents have the potential to not just reduce caloric intake, but also curb cravings for alcohol, nicotine, and recreational drugs, and perhaps mitigate other compulsive behaviors like shopping and gambling. Predictably, the cure to the ills caused by our overconsumption culture appears to be another example of conspicuous consumption—use of an expensive pharmacological agent. Yet, if these agents can rescue us from the irresistible overindulgence that is so common in contemporary America, they might be our best hope.

Abbreviations:

AUD

Alcohol Use Disorder

CVD

Cardiovascular Disease

DALYS

Drug-related Disability-Adjusted Life Years

eGFR

Estimated Glomerular Filtration Rate

GIP

Gastric Inhibitory Polypeptide

GLP-1RA

Glucagon-like peptide 1 agonists

HF

Heart Failure

HFpEF

Heart Failure with Preserved Ejection Fraction

T2D

Type 2 Diabetes

MACE

Major Adverse Cardiovascular Events

MASLD

Metabolic Dysfunction-Associated Steatotic Liver Disease

MI

Myocardial Infarction

NAc

Nucleus Accumbens

OSA

Obstructive Sleep Apnea

PCOS

Polycystic Ovarian Syndrome

RCT

Randomized Placebo-controlled Trials

UACR

Albumin-to-Creatinine Ratio

US

United States

VTA

Ventral Tegmental Area