The lixisenatide group saw an average weight loss of 0.6 kg, whereas the insulin glulisine once-daily and three-times-daily groups experienced average weight gains of 1 kg and 1.4 kg, respectively . The 2-step titration approach was used to randomly assign 446 T2DM patients to either placebo or 20 μg of lixisenatide once daily . However, the average weight reduction was 0.2 kg in lixisenatide group and 0.2 kg gain in the placebo group without any significant differences . In total, 484 individuals were randomly assigned to receive either a placebo or 20 μg of lixisenatide once a day in this multicenter, randomized, double-blinded research . Nature: Dozens of new obesity drugs are coming: 减脂增肌才是王道 Alogliptin increased body weight (from 66.5 ± 19.2 kg to 67.6 ± 19.3 kg), BMI (from 25.4 ± 6.1 kg/m2 to 25.8 ± 6.3 kg/m2), and fat mass (from 20.3 ± 12.8 kg to 21.8 ± 14.5 kg) substantially more than metformin did . In total, 84 Japanese people with poorly controlled T2DM were included in randomized research to compare the effectiveness of alogliptin (25 mg, once daily) and metformin (1000 mg, twice daily) on their body composition . Whether used as a monotherapy or in combination with other anti-diabetic drugs, alogliptin has demonstrated a decrease in HbA1c and is generally well-tolerated . Oral DPP-4 inhibitor alogliptin (Figure 1g) has largely been studied in phase II/III trials with T2DM patients . In the linagliptin and empagliflozin groups, there was an average difference of −1.80 kg in the mean body weight change from baseline to 24 weeks between both group . Participants in a 68-week, phase III trial lost an average of nearly 23% of their body weight with this approach, according to Novo Nordisk, the company behind the drug. There is hope that with the introduction of generic, and potentially less expensive SGLT2i and GLP-1RA, there will be more widespread use of these agents, along with more education of healthcare providers on the risks/benefits of these medications which provide robust cardio-renal protection. Compared with oncology, the role of precision medicine in diabetes management is less clear given the heterogeneous nature of T2DM, and the fact that diabetes medications are usually selected based on comorbidities, cost and side effects, rather than on the specific pathophysiology underlying disease in the individual patient. The DiRECT study in the UK assessed whether intensive weight management within routine primary care increased remission of T2DM in patients diagnosed within the past six years and not on insulin42. We can only say that the great success in refining hypertension treatment, so far in the last 50 years is truly only the beginning of a long journey.Nursing homes and other long‐term care facilities were the site of major outbreaks in the early stages of the pandemic, and residents with Alzheimer's and other dementias were particularly vulnerable.In obese people with a BMI greater than 35 kg/m2, the experiment found that metformin treatment significantly reduced BMI as compared to baseline .Semaglutide and cardiovascular outcomes in patients with overweight or obesity who do not have diabetes.Long‐term care services include home‐ and community‐based services and services delivered in assisted living residences and nursing homes.Medicare is a federal program for individuals age 65 and older, though individuals younger than 65 with certain disabilities, end‐stage kidney disease or amyotrophic lateral sclerosis (ALS) also qualify for Medicare.In PIONEER 6, a randomized, double-blind, phase 3 trial, 3183 individuals with T2DM with cardiovascular risks were randomly assigned to receive 14 mg of oral semaglutide or a placebo .Health authorities and agencies across the world will need to work together to address issues with equity and access to affordable diabetes care. In order to assess the impact of empagliflozin on body weight and adiposity in individuals with T2DM, a study evaluated two cohorts of patients from five randomized trials . Liraglutide and semaglutide are two of the five Food and Drug Administration (FDA)-approved anti-obesity drugs that are FDA-approved agents for the treatment of type 2 diabetes mellitus (T2DM) patients. With technical advances, novel therapeutic drugs are being developed to target different mechanisms underlying the pathogenesis of obesity; this could significantly impact the treatment of obesity and lead to more sustainable changes in weight and overall health. Shares of Altimmune have jumped more than 140% since Nov. 30, when the company released mid-stage trial data showing that its injectable drug caused 15.6% weight loss on average after 48 weeks. That trial is crucial because Novo Nordisk is waiting to see that data before filing for approval of the oral weight loss drug, said Cowen's Nedelcovych. Mixed insurance coverage will likely weigh on sales of Zepbound and other weight loss drugs in 2024, but Eli Lilly has already secured some coverage for the drug. Results from that trial could come out next year after initial data from separate studies examining Zepbound as a potential treatment for other health conditions, including heart failure. As a once-weekly injection, it revolutionized obesity pharmacotherapy. Semaglutide was approved in 2021 as Wegovy for weight management. However, it was never approved in the U.S. and was withdrawn by the EMA in 2008 due to increased risk of depression and suicidal ideation. A person who lives from age 70 to age 80 with Alzheimer's dementia will spend an average of 40% of this time in the severe stage.487 Much of this time will be spent in a nursing home (see the Use and Costs of Health Care, Long‐Term Care and Hospice section). Although the number of deaths from other major causes decreased significantly or remained approximately the same in the past two decades, official records indicate that deaths from Alzheimer's disease increased significantly. In many ways this echoes the discussion about dying with or from Alzheimer's disease discussed in this section. Overview of GLP-1R Agonists and Their Mechanism of Action in Weight Reduction Among the patients who completed 4 years of treatment, the percentage of patients who achieved at least 5% weight loss was significantly higher in the orlistat group (52.8%) than in the placebo group (37.3%). In the Xenical in the Prevention of Diabetes in Obese Subjects (XENDOS) study, a longitudinal study of patients using orlistat, the mean weight loss from the baseline was significantly greater with orlistat than with the placebo (10.6 kg vs. 6.2 kg) after 1 year and the significantly greater weight loss was maintained after 4 years (5.8 kg vs. 3.0 kg). From this perspective, in this review, we discuss obesity treatment strategies, focusing on pharmacological approaches with anti-obesity drugs approved for long-term use in patients with obesity. Because obesity contributes to many diseases, medications to help patients lose weight and sustain weight loss could potentially lead to improvements in multiple domains.Mean change in body weight was -13.3% with semaglutide and -2.6% with placebo over 52 weeks.Amgen is developing maridebart cafraglutide, known as MariTide, a long-acting peptide-antibody conjugate designed to increase GLP-1 receptor activity while inhibiting GIP receptor activity.Vildagliptin and metformin were used in combination therapy, which reduced the body weight loss ratio by 0.22 when compared to metformin monotherapy .Discontinuation of treatment related to adverse effects including nausea, vomiting, constipation, dry mouth, and dizziness has been reported .The blood pressure increases were greater atweek 8 for naltrexone/bupropion with mean placebo-adjusted systolic anddiastolic blood pressure changes of +2.4 mmHg and +2.1 mmHg, respectively,suggesting that this combination drug therapy raises blood pressure to a greaterdegree early in treatment before weight loss has occurred.It is therefore unsurprising that anti-obesity drug discovery programmes have been littered with false starts, failures in clinical development, and withdrawals due to adverse effects that were not fully appreciated at the time of launch.This meta-analysis of 14 RCTs found that interventions lasting 6 months or less were effective at achieving weight loss. 7.1. Potential impact of changing the trajectory of Alzheimer's disease Because lecanemab and donanemab have been approved recently (in 2023 and 2024, respectively), their effectiveness beyond the length of their clinical trials is not yet fully established.Treatment of animals with most sympathomimetic drugs reduces brain norepinephrine; treatment with fenfluramine does not.Results for weight change are reported from intention to treat analyses, generally with the last observation carried forward.“We’re going to see that there are different medicines that work better for different groups of people,” says Louis Aronne, an obesity specialist at Weill Cornell Medicine in New York City who consults for drug makers.The care provided to people with Alzheimer's or other dementias is wide‐ranging and in some instances all‐encompassing.Phenylpropanolamine was given GRAS status as an appetite suppressant based on an analysis of weight loss in published studies (98-100).An FDA Advisory Panel met on September 16, 2010, but rather than approving the drug, they voted 9-5 against approval based on two concerns, one about efficacy of the drug and the other about its safety. However, J.P. Morgan Research expects coverage to eventually improve, especially for obesity treatment. “Plus, the weight loss benefit from CGMs, while not quite comparable to that of GLP-1s, is nevertheless material, especially considering how much more affordable they are.” How will GLP-1s impact other technologies used to treat diabetes and obesity? There is also scope for biotech firms to explore, through clinical trials, how certain medications work in tandem with GLP-1s. Likewise, the rise of GLP-1s will shape diabetes treatment. Prior to 2019, the survey did not include caregivers of recipients for whom dementia was not their main condition, so these numbers were imputed using data collected in 2019 by the National Alliance for Caregiving (NAC)/AARP survey. The module asks a series of follow‐up questions, including asking the caregiver to identify what the main health problem, long‐term illness, or disability that the person they care for has. This module identified respondents age 18 and over who had provided any regular care or assistance during the past month to a family member or friend who had a health problem, long‐term illness or disability. Now adoption of these medications is gaining strength internationally, bolstering their potential market. Drugs that treat obesity have become increasingly popular in the past three years, especially in the U.S. The Centers for Disease Control and Prevention estimates that obesity-related medical costs in the US were about $173 billion in 2019. “The obesity market is still in its early stages,” Chris Shibutani, senior biopharmaceuticals analyst in Goldman Sachs Research, writes in the team’s report, noting there are uncertainties around the assumptions in the team’s model. A study from FAIR Health published in May 2025 reports that more than 2% of U.S. adults took a GLP-1 for weight loss in 2024. In 2021, attention to obesity medications exploded in popularity and media attention with the approval of semaglutide for obesity treatment under the brand name Wegovy. Before 2012, there were few weight loss medications approved by the FDA. Aspirin and non-steroidal anti-inflammatory drugs might increase circulating levels of chromium and increase the risk of adverse effects.Small trials on NB and Phentermine/Topiramate have shown some safety and efficacy on total body weight loss.Diabetes is an ancient disease and for centuries extreme diets and herbal remedies were used to treat diabetes symptoms.When these data were not reported, we used other data provided in the study for calculating the change (21).The suggestion for the use of GLP-1 receptors agonist is based on the availability of indirect evidence on cardiovascular risk reduction in patients with diabetes mellitus, LEADER trial for liraglutide157 and SUSTAIN trial for semaglutide.158 There was no signal of increased CVD in patient with obesity on liraglutide.The weight mean difference in patients receiving sitagliptin alone was −0.99 kg, while it was −1.09 kg in those receiving sitagliptin plus metformin .Gelesis100 was not significantly more effective in individuals with prediabetes or drug-naïve T2D with respect to mean percent change in body weight, which had been a notable observation in the pilot study First Loss of Weight (FLOW) (112).Side effects due to Gelesis100 are commonly gastrointestinal, including abdominal distension, infrequent bowel movements, or dyspepsia. Unlike stimulant-based medications, Orlistat worked in the gut, not the brain. But because it’s only meant for short-term use, it’s not a standalone solution for long-term weight control. It showed relatively safer results when used alone, and it remains FDA-approved today for short-term weight management. It was pulled from the market in 1997 after studies linked it to serious heart valve damage and pulmonary hypertension. People were losing weight quickly and seemingly effortlessly. Historically, obesity has been considered a behavioral and lifestyle condition among people lacking the willpower to moderate eating habits and exercise regularly. The SELECT results "are going to put pressure on insurance companies" to cover those drugs, he said. Coverage for Mounjaro ($1,023 per month) to treat diabetes varies based on an individual's insurance plan and drug benefits. Results like these may well prod government and private insurers to reimburse more patients for the high price tag of weight-loss prescriptions. Mounjaro is currently only approved by the Food and Drug Administration to treat diabetes, but the company has filed for FDA approval of Mounjaro specifically to treat obesity, which could come later this year or in early 2024. Food and Drug Administration with academic groups around the country assembled enough information to convince the FDA that up to 30% of the patients treated with fenfluramine (alone and in combination with phentermine) might develop valvular heart disease (140). The second set-back for fenfluramine and, by association, for phentermine occurred in July 1997 when the first case-series of valvular heart disease in patients taking Fen-Phen appeared in the prestigious New England Journal of Medicine (139). When the dramatic weight loss with Fen-Phen began to circulate widely in the 1990’s, fenfluramine and phentermine use exploded in popularity across the country. However, fenfluramine behaves differently and many who took the drug complained of a dysphoria, and it was not used to replace amphetamine-drug abuse in substitution trials. It was given a Schedule IV designation by the Drug Enforcement Agency because of its chemical similarity to other sympathomimetic anorectic drugs with abuse potential. A reduction in body weight of 5-10% significantly lowers inflammatory and pro-thrombotic makers, as well as chronic disease incidence (13,14). The associations between obesity, central obesity (increased waist circumference, especially intra-abdominal/visceral fat) and the risks for cardiometabolic diseases as well as obstructive sleep apnea, asthma, and nonalcoholic fatty liver disease (NAFLD) are well established (8,9). Obesity is a major risk factor in the development of cardiovascular disease (CVD), type 2 diabetes (T2D), musculoskeletal disorders, and several cancers (2). This long history of phentermine has already proven that it’s a survivor despite the many other weight loss drugs in the market simply because it is safe and effective. Both the generic phentermine and branded phentermine are still among the most prescribed weight loss drugs. However, the study also revealed that stopping the Fen-Phen medication will result to regaining of weight even despite continuing other supportive weight loss treatments. It was in the early 1950s when phentermine was introduced as a highly effective weight loss drug and anti-obesity drug. Based on the results, the investigators concluded that intervention with a drug and nutritional–hygienic advice was better compared to only nutritional–hygienic advice for treatment of mild hypertension. The success of this study opened up the treatment option to 50 million people in US alone. For the EWHPE trial (20, 21), 840 men and women over 60 years old, with a systolic blood pressure in the range 160–239 mmHg and a diastolic pressure in the range 90–119 mmHg, were randomized to receive active treatment (hydrochlorothiazide with triamterene) or matching placebo. An extensive meta-analysis of ephedra and ephedrine with andwithout caffeine for weight loss and improving athletic performance showed a 2.2to 3.6 fold increase in the odds of psychiatric, autonomic, or gastrointestinalsymptoms and heart palpitations. This legislation gave rise to wide spreaduse of ephedra and caffeine sold as a dietary supplement for weight loss. Sibutramine, a norepinephrine and serotonin reuptake inhibitor that actsby decreasing food intake, was approved in 1997 for the long-term treatment ofobesity. CB-1 antagonists thatdo not cross the blood brain barrier are not anticipated to have dose limitingside effects on anxiety and depression when translated into humans and furtherdevelopment in this area has the potential for future clinical trials 24, 25. With respect to nutritional content, sodium and saturated fat content may be of particular interest to clinicians given the effects of these nutritional components on blood pressure and lipid measures. Clinicians should discuss these factors when counseling patients on meal replacement programs as dissatisfaction with meal replacement product may contribute to discontinuation. Whey, which is protein derived from milk, is used in many meal replacement products, and patients with lactose intolerance may be unable to tolerate these dairy-containing products. Program fees, and particularly the costs of meal replacements, can be financially prohibitive to many patients. Research participants may represent an activated sample, and many trials offer incentives to participants through waiver of program fees or other methods. One published RCT reported weight reductions of 1.8 kg at 6 months with Lose It! In summary, there is clear evidence to support OPTIFAST’s 12-month weight-loss efficacy and safety. OPTIFAST is offered as part of a medically supervised weight-loss program, and costs may be high if program participation is not covered by insurance. In summary, there is clear evidence to support Medifast’s 12-month weight-loss efficacy and safety. Among trials reporting adverse events, serious adverse events were rare (16). Higher income levels correlate with lower discontinuation rates, particularly among patients with type 2 diabetes. Among adults with diagnosed diabetes, 33.3% of those aged used GLP-1 injectables, compared to 20.8% of those 65 and older. Adults aged are significantly more likely to stop treatment compared to those aged 35 and older. Research reveals important demographic differences in how long patients remain on GLP-1 medications. Methodological quality of included studies and confidence in the estimates The pooled SCALE data was also used to evaluateearly weight loss as a predictor for responders. Due to the concernabout neuropsychiatric symptoms from a centrally acting obesity medication,these symptoms were evaluated with validated questionnaires and there was nosignificant difference detected between the liraglutide and placebo groups indepression, anxiety, suicidal ideation or suicidal behavior. The Impactof Weight on Quality of Life-Lite questionnaire showed an improvement in theliraglutide group (11.0) compared to the placebo group (8.1) but this did notreach clinical significance. The reduction in the apnea-hypopnea index was greater in theliraglutide group (12.2 vs. 6.1) as was the weight loss (5.7% vs 1.6%). The conversion to diabetes was 2% in the liraglutide group and 6% inthe placebo group with the liraglutide group taking 2.7 times longer on averageto convert. Some weight loss medications have been on the market for many years, and new ones emerge frequently. Most medications are prescribed for someone with a BMI of 30 or greater, or a BMI of 27 or greater if the person has weight-related health conditions. Determining whether someone is a candidate for weight loss medications begins with BMI. 3.3. Payment models to support the dementia care workforce Histamine is located in neurons in the brain, in mast cells scattered around the body, and in the gastrointestinal track. Arena, the manufacturer of lorcaserin conducted a new round of studies and on May 10, 2012, another FDA Advisory Panel was convened. An FDA Advisory Panel met on September 16, 2010, but rather than approving the drug, they voted 9-5 against approval based on two concerns, one about efficacy of the drug and the other about its safety. Following completion of Phase 3 studies (150), an application for approval of Lorcaserin for marketing was submitted to the US FDA. It is a selective serotonin (5-HT2C) receptor agonist (thereby avoiding potential for adverse effects on cardiac valves and pulmonary artery pressures induced by other serotonin receptors—see fenfluramine above), which reduced food intake in experimental animals and humans. And obesity is clearly a very serious metabolic disease. But we and others were finding with treating human subjects with GLP-1 in the very early days that you had to be very careful to keep the dose low, because many patients felt ill when they were eating. We worked together, and we finally infused GLP-1 into people with type 2 diabetes and could show that the blood glucose came to completely normal levels in four hours, while insulin was stimulated and glucagon was inhibited. This was interesting, because people with diabetes have too much glucagon and that glucagon causes high blood sugar. SGLT-2 inhibitors are drugs that offer a means of managing hyperglycemia in T2DM patients using insulin-independent mechanism . From week 26 through the completion of the trial, weights declined in the 2 alogliptin treatment groups by a range of 0.60 kg to 0.94 kg, but increased in the glipizide group during the same time period by a range of 0.86 kg to 0.97 kg . Alogliptin has generally favorable safety characteristics, a low risk of hypoglycemia, and effects that are weight-neutral . With a minimal risk of hypoglycemia and weight neutrality, linagliptin (Figure 1f) is a once-daily selective DPP-4 inhibitor that has been approved for use in the treatment of T2DM 65,66. Topiramate (trade name Topamax) is an antiepileptic agent that has been found to reduce body weight in patients with a variety of disorders including epilepsy, bipolar disorder, and binge eating disorder (153). Dapagliflozin was recently approved by the FDA for the treatment of heart failure in individuals with or without T2D based on the results of the DAPA-HF trial (142). The fourth SGLT2 inhibitor, ertugliflozin, also resulted in about 2kg weight loss over placebo in adults with T2D treated for 26 weeks (136). In the landmark EMPA-REG CVOT, average placebo-subtracted weight loss of about 2 kg was maintained out to 220 weeks with empagliflozin 25 mg (135). Treatment with pramlintide (up to 240 ug three time daily) for 16 weeks resulted in a placebo-corrected reduction in body weight of 3.7% (P131). A pilot study of Noom integration into the National Diabetes Prevention Program reported a significant mean weight reduction from baseline of over 6.0% at 65 weeks (40–41). In summary, few RCTs have evaluated the weight-loss efficacy of My Fitness Pal, and the one long-term RCT showed no significant weight loss difference from control. In one study, My Fitness Pal users achieved weight reductions of 2.2 kg at 12 months, which were not significantly greater than those of control participants (37). In the phase II study 26% of subjects on ecopipam 100mg/d lost 5% of body weight compared to 6% on placebo (p21]. Subjects on active drugs demonstrated weight loss ofapproximately 0.5 pounds (0.23 kg) per week more than placebo (p8]. And some researchers think that because these drugs act through biological mechanisms, they will help people to understand that a person’s body weight is often beyond their control through lifestyle changes alone. Nutter is concerned that people might start these treatments—whose side effects, such as nausea and vomiting, can be severe—to escape weight stigma, rather than to serve a true health need. STEP TEENS garnered semaglutide’s FDA-approval for treatment of obesity in pediatric and adolescents aged 12 years and older, demonstrating 16.1% weight loss with semaglutide vs 0.6% weight gain with placebo over 68 weeks (92). Semaglutide Treatment Effect in People with obesity (STEP) trials 1-4 evaluated the effect of semaglutide 2.4mg once weekly on weight loss in patients with overweight or obesity, with and without T2D (86-89). For participants with obesity and moderate/severe obstructive sleep apnea, liraglutide 3.0 mg treatment resulted in significantly greater reductions than placebo in apnea-hypopnea index, body weight, SBP, and HbA1c levels (76). Both 56-week, randomized, placebo-controlled, double-blind clinical trials demonstrated significantly greater mean weight loss than placebo (8% vs. 2.6% in SCALE Obesity and Prediabetes (28) and 6.0% vs. 2% in SCALE Diabetes (73). In a 2-year trial, Davidson et al. reported less weight regain rates and lower levels of serum glucose and insulin in patients maintained on a 120 mg three times per day dose of orlistat, as compared to those on placebo (54). Savanna DiCristina, a Northeastern assistant clinical professor of pharmacy and health systems sciences, has witnessed the increase as a pharmacist at a health clinic for older, low-income adults. It’s just like every other drug, they don’t stay on it for many reasons. But if they start to develop cardiovascular disease or cancer or depression, then there’s something to do. Have you ever visited a diabetes hospital? And a 15 percent weight reduction is pretty remarkable too, right? Patients and doctors alike were thrilled with the results and for the first time it appeared that Americans with obesity were winning the battle of expanding waistlines. This was followed by a single center NIH-funded trial of fenfluramine and phentermine lasting 4 years (137). The first set-back for fenfluramine occurred in 1981 when the first 2 cases of pulmonary hypertension were reported (134), similar to the earlier reports of pulmonary hypertension in patients treated with aminorex. With this data in hand, dexfenfluramine was approved by the US FDA for management of obesity in the United Stated in 1994. When this was recognized, The International Dexfenfluramine (or INDEX) trial was designed to establish the safety and efficacy of dexfenfluramine (133). Further evidence was provided when Zhao et al. demonstrated alterations in gut flora triggered by liraglutide among simply overweight and T2DM overweight rats . This was further validated by research carried out by Wang and colleagues, wherein the GLP-1RA known as liraglutide showed potential in altering gut microflora, thereby promoting lean-related characteristics aligning with weight reduction in mice with high blood sugar levels . These findings led to the hypothesis that an analog of GLP-1 could deter weight accumulation by regulating gut microbiota. In their research, they demonstrated how selective deletion of Glp1r located within visceral nerves coupled with the administration of liraglutide increased body mass or escalated food consumption among organisms consuming standard or high-fat diets. Similarly, Kreiger and his colleagues conducted an extensive study to illustrate the integral role of GLP-1 receptors within vagal afferent neurons (VANs), termed GLP-1R. The combination of fenfluramine and phentermine—“fen-phen”—was a popular treatment by the 1990s. From DNP’s toxicity to the life-changing potential of tirzepatide, each era has left an indelible mark on public health and clinical practice. The FDA's approach has matured, now demanding long-term cardiovascular outcome trials and real-world safety data before or soon after approval. The recent wave of effective medications has also transformed public perception. Nutritional supplements/‘black market’ pharmaceuticals Although researchers are still chipping away at obesity’s complex combination of causes—including genetics, environment and behaviour—many support the idea that biology plays a significant part. Eli Lilly, for example, has a ‘bridging programme’ for Mounjaro—tirzepatide for type 2 diabetes—under which the medication can cost as little as $25 for the first three months. And some researchers are investigating the monoclonal antibody bimagrumab, which increases muscle mass while decreasing fat. And biopharmaceutical company Amgen, based in Thousand Oaks, California, is pursuing a drug that activates the GLP-1 receptor while thwarting the GIP receptor. In clinical trials, obese adults with at least one weight-related health issue lost around 8% of their starting weight over the course of a year, compared with just 2-3% in those on placebo. Although there is no direct evidence regarding the safety and effectiveness of liraglutide 3.0 mg on cardiovascular disease, it is the most preferred drug for patients with obesity and type 2 diabetes mellitus. Phentermine/topiramate CR has shown the strongest weight loss effect of any anti-obesity drug but the risk of neuropsychiatric reactions requires strict pharmacological monitoring. Novartis, a pharmaceutical company in Basel, Switzerland, discontinued the drug’s development in 2017. Bimagrumab began as a drug candidate for age-related muscle loss and other conditions that deplete muscle. But he remains more than 10% below his peak weight, and his muscle mass has held relatively stable. The experimental drug that Cook took, bimagrumab, works in just this way. Lee, who first discovered myostatin in the 1990s, consults for several drug companies. These costs include Medicare deductibles, copayments and coinsurance; other health insurance premiums, deductibles, copayments and coinsurance; and services not covered by Medicare, Medicaid or other sources of support. They are for Medicare deductibles, copayments and coinsurance; other health insurance premiums, deductibles, copayments and coinsurance; and services not covered by Medicare, Medicaid or other sources of support. A long‐term care hospital provides specialized care, such as respiratory therapy, pain management and treatment for head trauma.1001 Benefits work in the same way that Medicare covers other acute care hospitalizations. A long‐term care hospital is an acute care hospital that specializes in caring for people who stay more than 25 days, on average. Even more concerning, 45% of individuals age 65 and older believed that Medicare would cover the cost of nursing home care.995 It is especially important to know that Medicare does not cover custodial care, that is, care to assist with activities of daily living, such as dressing and bathing. These guidelines are expected to be updated annually to reflect the rapidly evolving science, new evidence and practical experiences of health care professionals. As part of its Healthy Brain Initiative Cooperative Agreement with the Centers for Disease Control and Prevention, the Alzheimer's Association initiated focus groups to gather perceptions and attitudes about the early detection and treatment of Alzheimer's disease beyond what could be gleaned from the survey. Among those surveyed, a majority of Hispanic (80%), Black (77%), Native (74%), and Asian Americans (73%) believed it likely that a treatment will be developed in the next decade to prevent Alzheimer's disease. These responses mostly align with public views on future Alzheimer's treatment reported in 2022, with a shift toward greater optimism about a future treatment to stop disease progression (60% of Americans 18 and over in 2022 versus 81% of Americans 45 and older in 2025).1064 Developing and maintaining healthy eating habits and increasing physical activity may help you regain less weight or keep it off. Your health care professional may also Possible side effects vary by medication and how it acts on your body. Most weight loss takes place within the first 6 months of starting the medication. In 1997 the drug cocktail fen-phen was removed from the US market after it became clear it caused heart valve damage. Explore manufacturer savings programs (which can reduce costs to $245-$550/month), patient assistance programs, or discuss alternative medications with your provider. Real-world results are typically lower than clinical trial outcomes, averaging 8-12% depending on the medication and patient adherence. Individual insurance policies should be checked carefully. Acarbose has mild weight loss effects and metformin and sodium-dependent glucose cotransporter proteins-2 (SGLT-2) inhibitors have modest weight loss effects; however, some glucagon-like peptide-1 (GLP-1) receptor agonists had the greatest impact on weight loss. However, guidelines suggest different weight targets are set depending on the complications, such as 5-15% weight loss for metabolic syndrome, type 2 DM and cardiovascular disease, 7-8% for obstructive sleep apnea and asthma, and 10-40% for steatohepatitis (Garvey et al., 2016). Weight loss aims to improve obesity-related complications and patients’ health and quality of life. At Bodyline Clinic, our doctors and nurse prescribers are regulated by the Care Quality Commission (CQC), and we have been providing Phentermine to thousands of patients within our fully supported medical weight loss programmes.The combination of naltrexone, an opioid receptor antagonist, and bupropion, a norepinephrine-dopamine reuptake inhibitor, is used for the management of obesity .A meta-analysis published in 2001 evaluated the effect of guar gum as a weight-loss supplement in a total number of 203 subjects.Senate Select Committee held their first hearings on the misuse of anti-obesity medications (94).The meta-regression results showed that medication categorisation impacts body weight, while the type of mental disorder and the presence of obesity-related comorbidities did not significantly affect the outcomes.Most prescriptions were issued by advanced practice practitioners (APP) and primary care physicians (PCPs) and internists.Several short-term placebo-controlled studies of phentermine have shown elevations in pulse or smaller decreases in pulse and/or blood pressure than would be expected given the degree of weight loss.3But these types of drugs have also attracted controversy, not least after admissions by drug makers that patients would likely regain weight once they ceased taking the medication. On average, Medicare beneficiaries age 65 and older with Alzheimer's or other dementias paid $10,564 out of pocket annually for health care and long‐term care services not covered by other sources (Table 16).941 This includes the cost of long‐term nursing home care for individuals not eligible for Medicaid. Total average per‐person health care and long‐term care payments in 2024 dollars from all sources for Medicare beneficiaries with Alzheimer's or other dementias were nearly three times as great as payments for other Medicare beneficiaries in the same age group ($44,814 per person for those with dementia compared with $15,053 per person for those without dementia).A15,941 On average, individual Medicare beneficiaries age 65 and older with Alzheimer's or other dementias paid $10,289 out of pocket annually for health care and long‐term care services not covered by other sources.941This excludes the cost of long‐term nursing home care for individuals not eligible for Medicaid. Medicare and Medicaid are expected to cover $246 billion, or 64%, of the total health care and long‐term care payments for people with Alzheimer's or other dementias. The costs of health care and long‐term care for individuals with Alzheimer's or other dementias are substantial, and dementia is one of the costliest conditions to society.940 Total payments in 2025 (in 2025 dollars) for all individuals with Alzheimer's or other dementias are estimated at $384 billion (Figure 15), not including the value of informal caregiving that is described in the Caregiving section. Nonetheless, gastrointestinal side effects continue to be the main reason for discontinuation. However, due to gastrointestinal side effects, it had significant withdrawal rates 140,141. With 3 mg, 1.8 mg, and placebo, respectively, an average decrease of 6.4 kg, 5 kg, and 2.2 kg was seen at week 56 . When reported, there were no serious adverse events or other harmful effects described with the use of My Fitness Pal (36–37). Of the 2 studies reviewed, 1 reported only completers’ analyses; attrition ranged from 25–32%. Continued engagement with platforms like My Fitness Pal may be an issue, as one study found that application engagement markedly declined after one month of follow-up (97% vs 55% participant log-ins at 1 and 2 months, respectively)(36). Additional long-term studies are needed in order to support routine referrals by clinicians. In summary, there are no long-term RCTs testing the weight-loss efficacy and safety with Lose It!. According to the Centers for Disease Control and Prevention (CDC), in 2020, people age 75 and older had the highest numbers and rates of TBI‐related hospitalizations and deaths, accounting for about 32% of TBI‐related hospitalizations and 28% of TBI‐related deaths.246 In 2018 and 2019, falls were the leading cause of TBI‐related deaths among those 75 and older.242 A number of different air pollutants have been studied in relation to cognition, cognitive decline and dementia itself. More recent research incorporating these technological advances suggests that rather than reducing the risk of developing Alzheimer's brain changes, formal education may help sustain cognitive function in mid‐ and late life and delay the development of symptoms even though brain changes may be present.174, 175 The addition or avoidance of no single food, beverage, ingredient, vitamin, multivitamin or supplement has been proven to prevent, delay, treat or cure Alzheimer's or any other dementia.167 More research is needed to better understand the differences in the study outcomes and the mechanisms by which physical activity may affect cognitive function across the lifespan. Analysis of weight change is challenging and can be complicated by nonlinear weight change during drug use. The Agency for Healthcare Research and Quality commissioned a technology assessment report (29) comparing second-generation antidepressants, but a quantitative meta-analysis was not performed on the outcome of weight change. Our findings are in general consistent with other systematic reviews that evaluated single drugs or drug classes (26–30) and faced similar challenges. These particular investigations collectively imply that neuropathic interactions with liraglutide via neuronal GlpIR have significant effects on body weight regulation along with generating anorexic effects. The first GLP-RA liraglutide was approved for treating obesity, as it promotes reduced food intake and weight loss. The effectiveness of medications observed in clinical trials does not show the same results in the real world, at least due to the lower adherence of patients, discontinuation of the therapy, and the lack of representativeness in participating in clinical trials. Yet, numerous antiobesity medications have noticeably fallen short due to their mediocre therapeutic impact and inferior performance over prolonged usage, coupled with intolerable side effects . Müller says that tirzepatide might be a more potent activator of the GLP-1 receptor, and that GIP might help to make GLP-1’s side effects more tolerable, allowing for higher doses.When compared to group A, these differences, however, were not clinically significant .Nonetheless, acarbose’s impact on individuals who were overweight and obese but did not have diabetes was recently investigated in a meta-analysis .One in three spousal dementia caregivers are “not at all prepared” for hospitalization.662 When people with dementia also have depression, behavioral disturbances or low functional status, their caregivers face a higher risk of emergency department visits and hospitalization compared with caregivers of people with dementia without these challenges.663, 664 Increased depressive symptoms among caregivers are linked to more frequent caregiver doctor visits, increased outpatient tests and procedures, and greater use of over‐the‐counter and prescription medications.664EMP 16 is a brand-new weight-loss combination product that was created as a prospective weight-loss product containing orlistat and acarbose .Rainbow diet pills, potent mixtures of multiple prescription medications with complex pharmacodynamic interactions, have been prescribed by physicians for more than 70 years.Between 2002 and 2022, the proportion of individuals with Alzheimer's who died in a nursing home decreased from 67% to 41%, and the proportion who died in a medical facility decreased from 14% to 5%.Records from Ancient Egyptian and Biblical eras through Greco‐Roman to Medieval times indicate that obesity was present throughout the major periods of history, although peoples of previous centuries would probably have experienced overweight and obesity as exceptional rather than normal. “We really need a variety of drugs … so that we can match the right treatment to the right patient.” The drug seems to cause even more weight loss than semaglutide, Yanovski says. Weekly injections of the drug lowered the risk of heart attacks, strokes and death due to cardiovascular disease in some adults, Cleveland Clinic cardiologist A. Companies are also exploring alternatives to once-a-week injections, which can be difficult to incorporate into people’s routines and come with manufacturing challenges.The global market for weight-loss medications could reach $150 billion by 2035.In their research, they demonstrated how selective deletion of Glp1r located within visceral nerves coupled with the administration of liraglutide increased body mass or escalated food consumption among organisms consuming standard or high-fat diets.What’s the full range of side effects?One group of researchers found that individuals with Alzheimer's or another dementia seen in the emergency department are more likely to be admitted to the hospital or a nursing home from the emergency department than are Medicare beneficiaries without Alzheimer's or other dementias.956 Additionally, individuals with Alzheimer's or other dementias are more likely to have at least one hospitalization, have at least one subsequent emergency department visit and be admitted to hospice in the 12 months following the initial emergency department visit.More innovative weight-loss pills may just be around the corner.The magnitude of weight loss achieved with semaglutide was unprecedented among pharmacologic interventions for obesity, making it a game-changer in the field of obesity management. The once-monthly injection entered phase 3 clinical trials for weight loss and type 2 diabetes in March 2025. Phase 3 trials for steatotic liver disease and weight loss are underway. We are likely to continue to see clinical trials include treatment of adiposity-related diseases as a component of obesity medication investigations. With fervent consumer demand for weight loss medications, combined with rising obesity rates, more medications are bound for the market in the coming years. Because obesity is a chronic disease, obesity medications should be used long term in combination with a healthy diet and exercise. For instance, GLP-1s may aid in the management of cardiovascular disease and heart failure, which around 9 mn obese patients suffer from. This could lead to a paradigm shift in health care and also impact other sectors, from biotech to food. J.P. Morgan Research forecasts the GLP-1 market will exceed $100 bn by 2030, fueled equally by diabetes and obesity usage. While used as an herbicide, photo developer, and in munitions production, a researcher at Stanford realized in 1933 that consuming the substance would also induce weight loss.Although there are no RCTs that specifically examined the efficacy ofphentermine/topiramate in patients with obesity and hypertension, data from thesubset of patients with hypertension support its use in this patient population.Other drugs are currently under consideration in clinical trials.Other benefits in addition to weight loss were also observed including improvements in glycaemic control, blood pressure and lipids.Interestingly, physicians often underestimate the impact of side effects on patients.Fucoxanthin, a marine carotenoid, is a potent antioxidant compound, and has potential application as anti-diabetic and anti-obesity effects in several animal models, including diabetic mice, Wistar rats, and diet-induced obese C57BL/6J mice 82, 83.The Global Burden of Disease study reports that overweight and obesity are the fourth leading risk for global deaths, and more than 4.7 million adults die each year as a result of overweight or obesity (6).In addition, DNP at doses that do not affect weight is being explored for its potential use in neurodegenerative disease where mitochondrial dysfunction is often observed. There are other dementia‐friendly efforts that encompass both medical and non‐medical professionals who work in a range of settings and contexts, including dementia‐friendly care for people living in hospitals;907, 908, 909 dementia‐friendly design for nursing homes, senior centers and similar settings;878, 910, 911 and dementia‐friendly neighborhoods to improve quality of life for local residents.912, 913 More research is needed on the effectiveness of these dementia‐friendly efforts as well as their implications for workforce development. As one example of collaborative dementia care, the Alzheimer's and Dementia Care Program is a health systems‐based model in which nurse practitioners with extensive training in dementia care, known as dementia care specialists (DCSs), co‐manage care with PCPs and community‐based partners. A major barrier to improving dementia care is fragmentation of care delivery, which occurs when patients receive care from many providers, but no single provider accounts for a substantial proportion of visits.887 Although seeing multiple providers may be clinically appropriate, providers do not often communicate or coordinate with each other in the care of their common patients. In the context of Alzheimer's disease and other dementias, CHWs can help dispel misconceptions and stigma, encourage earlier screening and clinical trial participation, and improve access and navigation to support services for members within their communities. Nursing assistants in various care settings and home health aides employed by Medicare‐certified home health agencies are required by federal regulations to complete at least 75 hours of entry‐level training and 12 hours of annual continuing education (although many states have set higher training requirements).862 Care for individuals with cognitive impairment is among the requisite training topics for nursing assistants, but not for home health aides. Related: Ozempic will give way to another quick-fix diet drug, then another and another, Northeastern expert predicts We know that the 24-h average BP per ABPM predicts hypertension outcome better than office BP – the standard used in almost all the trials cited above. Thus, we have to continue to strive to expand our knowledge of the physiology and epidemiology of hypertension and related diseases. Without understanding the disease (or possibly the complex of diseases that manifest as high BP), we cannot achieve true control over it. The similarly designed EQUIP trial comprised two phentermine/ER topiramate treatment arms (15 mg and 3.75 mg) and a placebo arm 75. CONQUER was a 56‐week, randomised, double‐blind, placebo‐controlled, phase III trial in which two phentermine/ER topiramate treatment arms (15 mg and 7.5 mg) and one placebo arm were initiated in conjunction with a 500 kcal/day dietary deficit 74. Weight loss was significantly greater in patients receiving the high‐dose combination treatment compared with high doses of both compounds alone. These authors concluded that intermittent phentermine was preferable because it was cheaper, gave equivalent weight loss, and reduced exposure to medication; although this runs counter to current concepts of chronic disease management in which continuous use is recommended. The group treated intermittently showed the effect of stopping and starting an active drug to placebo relative to continuous treatment. In one older study (118), a group of patients received a placebo, the second group received phentermine resin 30 mg/day, while the third group was treated with phentermine resin alternating with placebo at 1-month intervals. Serotonin suppresses appetite, ultimately resulting in weight loss. In the early 1990s, some doctors began prescribing a combination of fenfluramine and phentermine, known as “fen-phen,” for weight loss. At the same time, we should be mindful of the fact that the outlook for patients with diabetes today is much better than what they would have encountered in the 1920s or even in the 1970s. Can you stop taking GLP-1 medications without side effects? These medications treat obesity as a chronic condition requiring ongoing management. Most people discontinue within the first year, with only 40-63% remaining on treatment at 12 months depending on the medication and when they started. Will cessation of GLP-1RA after 2 years permanently impact regulating food intake and reduced body weight?It also poses adverse side effects like higher blood pressure, over stimulation, dryness of mouth, and urticaria.The ketogenic diet has become a popular trend in recent years, with many people turning to this low-carb, high-fat diet to help them lose weight and improve their overall health.In comparison to the multiple daily insulin group, which experienced an average gain of 0.8 kg, the lixisenatide/basal insulin combination group experienced a mean body weight reduction from baseline of 2.5 kg .Of note, insulin pumps and CGMS are expensive and primarily used in patients with type 1 diabetes mellitus (T1DM).As stated, saxagliptin, when administered alone has a weight-neutral effect on T2DM patients’ weight, or may even produce weight loss when administered in conjunction with metforminIn patients receiving beta-adrenergic receptor blockers, showing verified resistance to dietary therapy. Some, such as fluoxetine, were found to promote weight loss for up to six months, but not longer-term.60Bupropion, a norepinephrine and dopamine reuptake inhibitor, was tested as monotherapy for up to one year as a weight loss medication. In addition, there was a significantly lower incidence of progression to type 2 diabetes in the top-dose group (0.9%) vs. placebo (3.7%). In addition, 62% (recommended dose) and 70% (top dose) lost ≥5% of initial weight vs. 21% for placebo, with 37%, 48%, and 7% respectively losing ≥10% of initial weight. All underwent dose titration over 4 weeks to assigned dose followed by 52 weeks on drug or placebo. A recent study found that domestic partners of WW participants, who did not directly participate, also lost weight (20). Interestingly, weight loss benefits of participating in WW may extend beyond the individual taking part in the program. Of particular relevance to clinicians, one RCT found that WW participants lost more weight than subjects who received counseling from a primary care physician (19). In a small-scale clinical trial with 161 participants, people who received either 0.5 or 1.0 mg of tesofensine for 24 weeks experienced weight reductions of 11.3 and 12.8 kg, respectively.The proportion of patients with weight loss of at least 5% is 3.4, 2.3, and 1.7 times higher for phentermine/topiramate CR than for orlistat, naltrexone ER/bupropion ER, and liraglutide, respectively.Instead, the rainbow colors suggested personalized attention, a treatment uniquely crafted for the patient's individual weight loss requirements; a clearly insidious version of what might otherwise be termed “personalized medicine” today.Whey, which is protein derived from milk, is used in many meal replacement products, and patients with lactose intolerance may be unable to tolerate these dairy-containing products.The liraglutide group lost an additional 6.1% bodyweight compared to 0.2% additional body weight in the placebo group over 56weeks, and all subjects were given diet, exercise and weight counseling duringthe trial.This perception linked weight to behaviors and values, just as often happened with race, gender and class.Nothing is more valuable than the perspective of somebody who has excelled while being deep in the belly of the beast.Olestra can also interfere with the absorption of fat-soluble vitamins such as vitamins A, D, E, and K, raising concerns about the potential for nutrient deficiencies in people who consume olestra regularly. In clinical stage 0, individuals do not have symptoms of Alzheimer's disease, but have a deterministic gene that virtually guarantees that they will develop Alzheimer's. The Alzheimer's disease continuum represents the progression of Alzheimer's disease from brain changes that are unnoticeable by the person affected to brain changes and symptoms that severely impair daily function.53 How long individuals spend in each part of the continuum varies and is influenced by age, genetics and other factors.54 In 2024, revised criteria for diagnosing Alzheimer's and identifying where it is on this continuum (called staging) were published.53 These criteria incorporate recent advances in biomarkers to provide objective data for making a diagnosis and assigning a clinical stage (0 to 6) to the progression of the disease (Table 3A). Aspiration pneumonia is a contributing cause of death among many individuals with Alzheimer's dementia (see Mortality and Morbidity section). Contrave has a warning label addressing the risk of suicidal thoughts and behaviors, which DiCristina says is known as a “black box” warning because the alert has a black box around it to capture the user’s attention. They work by slowing the movement of food from the stomach into the small intestine, which appears to curb hunger so people eat less. Qsymia is known to cause birth defects, while Contrave comes with a “black box” warning label for the risk of suicidal thoughts and behaviors. Amphetamines also had noted appetite suppressant effects. One can think of the molecules of the body are sped up to the point that they cause actual thermogenic malfunctions. Dinitrophenol did indeed increase people’s metabolism, but it sped it up too much and caused nerve damage. This was also effective but to the detriment of the people who took it. In addition to dual activators, such as tirzepatide, there are also drug candidates such as MariTide (produced by the biopharmaceutical company Amgen in Thousand Oaks, California) that instead block GIP signalling while still activating GLP-1. At least five tirzepatide-like therapies are progressing through clinical trials, with the first expected to hit the market by 2028. Tirzepatide’s dual action is thought to contribute to its superior weight-loss results. This hormone further revs up energy metabolism and affects how the body stores and burns nutrients. An oral, small-molecule drug that activates the glucagon-like peptide 1 (GLP-1) receptor. These treatment schemes could be considered by physicians in other countries. This safety profile is in line with those reported in other studies 11, 22, 26. These results highlight the importance of a close clinical monitoring in the first weeks of treatment to reduce the attrition rates 27, 28, 29. Many religious orders prescribed fasting as a way to maintain discipline, which inadvertently led to weight loss. The Egyptians, for instance, used a mixture of herbs and spices, such as cumin and coriander, believed to aid digestion and promote weight loss. However, those who sought to lose weight relied on natural remedies and herbal treatments.