Geriatric Pharmacotherapy Case Series: GLP-1 RA for Weight Management in Older Adults.

Since the initial scientific statement on Secondary Prevention of Coronary Heart Disease (CHD) in the Elderly was published in 2002,1 several trends have continued that make an update highly appropriate. First, the graying of the US population and those of other industrialized countries has progressed unabated because more adults are surviving into their senior years. The number of Americans aged ≥75 years was estimated at 18.6 million in 2010, representing ≈6% of the population,2 and it is expected to double by 2050. The population aged ≥85 years is growing the most rapidly, with numbers expected to reach 19.5 million by 2040. In 2008, 67% of the 811 940 cardiovascular deaths in the United States occurred in people aged ≥75 years.3 In parallel to this increase in the older adult demographic, the number of Americans with CHD has increased to an estimated 16.3 million, more than half of whom are >65 years of age.3 Similarly, 7 million have had a stroke, the incidence of which approximately doubles with successive age decades after 45 to 54 years.3 Peripheral artery disease (PAD) affects 8 to 10 million Americans, the majority of whom are >65 years of age. Between 2015 and 2030, annual US costs related to atherosclerotic cardiovascular disease (ASCVD) are projected to increase from $84.8 billion to $202 billion.3 Moreover, given that ASCVD often undermines functional capacity and independence and increases reliance on long-term care, indirect expenses related to ASCVD are also expected to increase. Thus, the need for effective secondary prevention measures in the older adult population with known ASCVD has never been greater. Notably, the 2011 American Heart Association (AHA)/American College of Cardiology Foundation (ACCF) updated guidelines for secondary prevention of CHD broadened …

792-P: GLP-1 RA Therapy Increases Circulating Vascular Regenerative Cell Content and Decreases Inflammatory Burden in People with T2D

The cardiovascular (CV) benefits of glucagon-like-peptide-1 receptor agonist (GLP-1 RA) therapies are not well-established in women with breast cancer and type 2 diabetes (T2D). The primary objective of this study was to compare the incidence of major adverse cardiovascular events (MACE) in women with T2D and breast cancer receiving GLP-1 RA therapy versus non-GLP-1 RA diabetes medications. This retrospective study included women with T2D, diagnosed with breast cancer at ≥ 40 years old from December 16, 2014 to December 16, 2024 and having exposure to diabetes medications of interest (either GLP-1 RA or non-GLP-1 RA) within 5 years of these diagnoses. The primary end point, MACE, was a composite of myocardial infarction, ischemic stroke, coronary revascularization, cardiac arrest, or heart failure, within 5 years of the index date. Propensity score matching was performed. Participants were excluded from each individual outcome analysis if they had the outcome prior to the index date. Incidence rates, risk ratio (RR), 95% confidence interval (CI), and p-value were reported for each outcome. After matching, 19,608 patients were included in each cohort (mean age 64 years). Obesity and alkylating agents were more commonly reported in the GLP-1 RA cohort. Semaglutide was the most prescribed GLP-1 RA at index (45.1%). MACE occurred in 10.6% of the GLP-1 RA cohort and 13.4% of the non-GLP-1 cohort (RR 0.80, 95% CI 0.75-0.85, p < 0.001). Individual MACE end points, ischemic heart disease, and end-stage renal disease were significantly lower in the GLP-1 RA-treated cohort. GLP-1 RA use was also associated with a 61.6% relative risk reduction in all-cause mortality (RR 0.38, 95% CI 0.36-0.41, p < 0.001). Pancreatitis incidence was similar between groups (p = 0.057), whereas cholelithiasis was significantly lower with GLP-1 RA therapy (p < 0.001). This study demonstrated the potential CV benefit of GLP-1 RA therapies among a population of female breast cancer survivors with T2D. Randomized trial data are needed to confirm these findings.

Background: The evidence regarding the effect of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in patients with heart failure with reduced ejection fraction (HFrEF) is limited and conflicting, with some studies suggesting a favorable effect and some not. The aim of the study was to examine the safety and efficacy of GLP-1 RA therapy in a large national database of patients with HFrEF. Methods: In this observational retrospective cohort, data was obtained from the electronic medical records of Clalit Health Services, the largest health care organization in Israel. Between the years 2014 -2024, using a 1:1 matching, patients with HFrEF who were treated with GLP-1 RA were compared with those who were not. Outcomes included heart failure (HF) hospitalization and death. A subgroup analysis by body mass index (BMI), age, sex, HbA1C level and concomitant medications was conducted as well. Results: Out of 22,411 patients with HFrEF, 3023 initiated GLP-1 RA therapy after the diagnosis of HF was made. After a 1:1 nearest-neighbor matching, 3858 patients were matched and included in the study, with 1939 and 1919 patients in the GLP-1 RA group and the control group, respectively. Mean age of the cohort was 69, 33% female, and mean BMI was 29.9 kg/m2. While therapy with beta blockers and ACEI/ARB/ARNI was common within the cohort, only a third of the cohort was treated with SGLT2 inhibitors or mineralocorticoid receptor antagonists. Median follow-up time of the study was 30 months (17.06, 43.0). In a multivariable model which included multiple demographic and clinical variables, patients who were treated with GLP-1 RA were less likely to experience the primary outcome of death or HF hospitalization (HR 0.6, 0.53 – 0.68, p&lt;0.001) compared with the control group. The subgroup analysis revealed a robust favorable effect of GLP-1 RA across the entire spectrum of patients with HFrEF. Conclusion: In this large cohort study of patients with HFrEF, GLP-1 RA therapy in addition to standard guideline directed medical therapy was associated with a lower rate of death and HF hospitalization. Future randomized trials are needed to confirm these results.

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1 RA) have transformed the management of obesity and type 2 diabetes. Emerging reports describe accelerated facial soft-tissue deflation and periorbital changes among treated patients, often referred to as "Ozempic face." Given the thin skin and minimal subcutaneous tissue of the upper eyelid, rapid weight loss may exacerbate dermatochalasis and increase demand for surgical correction. This study evaluates whether GLP-1 RA therapy is associated with an increased rate of upper eyelid blepharoplasty.MethodsA retrospective cohort study was conducted using the TriNetX Research Network. Female adults aged 18 or older with diabetes mellitus and essential hypertension between January 2015 and January 2020 were identified. Patients prescribed GLP-1 RA comprised the exposure cohort; patients without GLP-1 RA served as controls. Follow-up extended up to five years. The primary outcome was upper eyelid blepharoplasty. Propensity score matching (1:1 nearest neighbor) was performed for age, race, BMI, and comorbidities. Kaplan–Meier survival analysis and Cox proportional hazards modeling were performed. A secondary analysis compared patients achieving weight loss without GLP-1 RA to matched controls with stable BMI.ResultsA total of 821,792 eligible female patients were identified, of whom 28,970 received GLP-1 RA therapy. After propensity score matching, 23,349 patients remained in each cohort. At five-year follow-up, 96 GLP-1 RA users (0.41%) underwent blepharoplasty compared with 36 controls (0.15%). GLP-1 RA use was associated with an increased hazard of blepharoplasty (hazard ratio 2.22; 95% confidence interval 1.51–3.26; p < 0.001). Kaplan–Meier analysis demonstrated shorter time to surgery among GLP-1 RA users. In the secondary analysis, non-GLP-1 RA weight loss was not associated with increased blepharoplasty incidence (hazard ratio 1.31; 95% confidence interval 0.89–1.93; p = 0.56).ConclusionsGLP-1 receptor agonist use is associated with a significantly increased rate and earlier timing of upper eyelid blepharoplasty compared with matched controls. Weight loss alone did not demonstrate the same association, suggesting a distinct pattern of facial remodeling related to GLP-1 RA therapy. As pharmacologic weight loss expands, plastic surgeons should anticipate increased demand for periorbital rejuvenation and counsel patients accordingly.

This meta-analysis evaluates the safety and efficacy of glucagon-like peptide-1 receptor agonists(GLP-1 RA) for the treatment of older adults with obesity compared to younger individuals. A systematic review was conducted following PRISMA guidelines (PROSPERO CRD420251074381). PubMed, Embase, and Scopus were searched until May 17, 2025, for randomized controlled trials and observational studies assessing GLP-1 RA in adults ≥ 65 years with obesity with or without type 2 diabetes. Random effects meta-analyses calculated the log odds ratios (LOR) for dichotomous outcomes and the mean differences (MD) for continuous outcomes, with equivalence testing via two one-sided tests (TOST) and meta-regression for baseline adjustments. Five studies involving 1229 participants were included. No significant difference in serious adverse events was found between older and younger adults (pooled LOR: 0.06, p = 0.9). Older adults had a trend toward lower frequency of nausea (LOR: -0.44, p = 0.06) but higher incidence of constipation (LOR: 0.72, p = 0.02) and hypoglycemia (LOR: 0.97, p < 0.001). Efficacy in metabolic and weight control was comparable. Additionally, one study suggested that liraglutide could reduce fat mass without worsening sarcopenia. GLP-1 RA therapy seems to be safe and effective in older adults with obesity, achieving similar effects on weight loss and glycemic control as in younger individuals.

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell disorder with potential progression to multiple myeloma (MM). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated potential anti-neoplastic properties. This study evaluated the association between GLP-1 RA use and clinical outcomes in individuals with MGUS and concurrent DM, overweight or obesity. A retrospective cohort study was conducted using the TriNetX global health research network. Adults with MGUS and either DM or overweight/obesity were identified. Propensity score matching (1:1) was performed, resulting in two balanced cohorts. The primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS), time to progression to multiple myeloma (MM) and major cardiovascular events, including myocardial infarction (MI), ischemic stroke, ischemic heart disease and heart failure (HF). Among 30,034 matched patients, 823 patients in the GLP-1 RA group and 2317 in the control group progressed to symptomatic MM or died. GLP-1 RA use was associated with significantly improved PFS [HR (95% CI): .63 (.58-.68)] and OS [HR (95% CI): .61 (.56-.66)]. A reduced risk of progression to symptomatic MM was also observed [HR (95% CI): .82 (.69-.98)]. GLP-1 RA users had lower cumulative incidence of MI, HF, ischemic heart disease, and stroke; however, these differences were not confirmed in time-to-event analyses. GLP-1 RA therapy was associated with significantly improved PFS and OS in MGUS patients with metabolic comorbidities. While fewer cardiovascular events were observed, these findings were not statistically confirmed over time.

The prevalence of obesity in older adults (people aged >60 years) is increasing in line with the demographic shift in global populations. Despite knowledge of obesity-related complications in younger adults (increased risk of type 2 diabetes, liver and cardiovascular disease and malignancy), these considerations may be outweighed, in older adults, by concerns regarding weight-loss induced reduction in skeletal muscle and bone mass, and the awareness of the ‘obesity paradox’. Obesity in the elderly contributes to various obesity-related complications from cardiometabolic disease and cancer, to functional decline, worsening cognition, and quality of life, that will have already suffered an age-related decline. Lifestyle interventions remain the cornerstone of obesity management in older adults, with emphasis on resistance training for muscle strength and bone mineral density preservation. However, in older adults with obesity refractory to lifestyle strategies, pharmacotherapy, using anti-obesity medicines (AOMs), can be a useful adjunct. Recent evidence suggests that intentional weight loss in older adults with overweight and obesity is effective and safe, hence a diminishing reluctance to use AOMs in this more vulnerable population. Despite nine AOMs being currently approved for the treatment of obesity, limited clinical trial evidence in older adults predominantly focuses on incretin therapy with glucagon-like peptide-1 receptor agonists (liraglutide, semaglutide, and tirzepatide). AOMs enhance weight loss and reduce cardiometabolic events, while maintaining muscle mass. Future randomised controlled trials should specifically evaluate the effectiveness of novel AOMs for long-term weight management in older adults with obesity, carefully considering the impact on body composition and functional ability, as well as health economics.

Background Weight gain and associated metabolic complications are increasingly prevalent among people with HIV (PWH), especially those initiating second-generation integrase strand transfer inhibitors (INSTIs). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are incretin-based therapies for diabetes that have been shown to result in substantial weight loss; however, studies of their efficacy in PWH are limited. We aimed to describe the prescribing practices and clinical outcomes of GLP-1 RA use among PWH. Methods We conducted a retrospective cohort study among PWH who were prescribed GLP-1 RAs at University of California, San Diego between 2/1/2021and 2/1/2023. Patients who were prescribed but never took GLP-1 RAs or those for whom weight data were not available after GLP-1 RA initiation were excluded. We collected baseline clinical data and calculated changes in weight, body mass index (BMI), and hemoglobin A1C (A1C) before and during receipt of GLP-1 RA. We conducted logistic regression to identify variables associated with more than 5% of total body weight loss. Results 227 patients met our inclusion criteria. Baseline characteristics are shown in Table 1. Ninety-nine patients (43%) were prescribed GLP-1 RAs for weight management alone without concurrent diabetes. Patients had received on average 15.2 months of GLP-1 RA therapy, with 92 (40.5%) achieving the maximum GLP-1 RA dose. On average, GLP-1 RA therapy resulted in a loss of 12 pounds, decrease in BMI by 1.8, and decrease in A1C by 0.5 among all patients and by 1.2 among patients with an A1C &amp;gt; 6.5 at baseline. In the multivariable analysis, higher baseline BMI [OR 1.07 (1.02-1.3)] and longer treatment duration of GLP-1 RA therapy [OR 1.04 (1.01-1.07)] were significantly more likely to be associated with &amp;gt;5% weight loss, whereas receipt of dulaglutide significantly decreased the likelihood of &amp;gt;5% weight loss compared to other GLP-1 RAs [OR 0.33 (0.17-0.66)]. Age, sex assigned at birth, race, ethnicity, ART regimen, baseline CD4 cell count, HIV viral load, and presence of diabetes were not predictive of weight change.Table 1.Baseline Patient Characteristics (N = 227)Table 2.Mean weight, BMI, and A1C before and during GLP-1 RA therapy for PWH Conclusion Use of GLP-1 RAs led to improvements in weight, BMI, and hemoglobin A1C among PWH and offers an additional strategy to address weight gain and related metabolic complications. Disclosures All Authors: No reported disclosures

Intensive glucose lowering in older adults with diabetes leads to increased risks with minimal benefits. Surveys indicate that clinician confidence for individualizing glycemic goals and regimens remains low. We created an interactive workshop and clinical tool kit to improve clinician knowledge of safe diabetes management in older adults. Finding the Sweet Spot was a 1-hour workshop taught by pharmacists to medical and pharmacy learners that introduced a five-step framework for diabetes management in older adults. The interactive presentation included cases and a clinical tool kit based on current recommendations from the American Diabetes Association and American Geriatrics Society. Pilot workshops were held for 6 months, allowing for real-time revisions based on feedback; final implementation occurred for 6 months thereafter. We evaluated learner self-efficacy (via a 5-point Likert scale) and knowledge (via multiple-choice questions) of diabetes management in older adults before and after the workshop. Thirty learners participated in Finding the Sweet Spot (70% medicine, 30% pharmacy). The percentage of confident learners increased from 55% to 97% (p < .05) after the workshop. All learners demonstrated improvements in knowledge, with the mean score on the knowledge assessment increasing from 61% to 80% (p < .05). Via open-ended feedback, learners expressed satisfaction and found the clinical tool kit especially helpful. Our Finding the Sweet Spot workshop demonstrated statistically significant changes in self-efficacy and knowledge among learners, indicating that this interactive workshop improves medical and pharmacy provider confidence and skills in caring for older adults with diabetes.

Insulin sensitizers and polycystic ovary syndrome: can a diabetes medication treat infertility?

Current treatment options for idiopathic intracranial hypertension (IIH) are limited by efficacy, safety, and sustainability concerns. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs), known for promoting weight loss and metabolic regulation, may offer a novel therapeutic approach. To assess whether GLP-1 RA therapy is associated with improved clinical outcomes in patients with IIH compared with conventional therapies. This retrospective cohort study was conducted using data from the TriNetX US Collaborative Network between 2005 and 2024, with a follow-up duration of 1 year. Electronic health records from 67 health care organizations across the United States were examined. Participants were patients 18 years and older who had IIH. Initiation of GLP-1 RA therapy within 6 months of IIH diagnosis. The control group included patients managed with conventional treatments, such as acetazolamide, topiramate, and dietary counseling, without GLP-1 RA exposure. Outcomes included use of non-GLP-1 RA medication, symptoms and signs, procedures, and mortality over 1 year. Outcomes were expressed as risk ratios (RRs) with 95% CI. A total of 44 373 patients with IIH were identified. Before propensity score matching, the cohort included 603 GLP-1 RA users and 43 770 nonusers. The GLP-1 RA group was older (mean [SD] age, 43.2 [13.0] vs 35.5 [14.3] years; P < .001) with fewer male patients (n = 60 [10.0%] vs n = 5879 [13.5%]; P = .01) and a similar number of female patients (n = 522 [86.6%] vs n = 36 796 [84.3%]; P = .13). After matching, 555 GLP-1 RAs users were compared with 555 nonusers. GLP-1 RA use was associated with lower medication use (RR, 0.53; 95% CI, 0.46-0.61; P < .001) and reduced headaches (RR, 0.45; 95% CI, 0.35-0.58; P < .001), visual disturbances or blindness (RR, 0.60; 95% CI, 0.41-0.88; P = .007), and papilledema (RR, 0.19; 95% CI, 0.10-0.34; P < .001). Procedures (RR, 0.44; 95% CI, 0.30-0.63; P < .001) and mortality (RR, 0.36; 95% CI, 0.18-0.73; P = .003) were lower in the GLP-1 RA group, but mean (SD) body mass index (BMI) did not differ at follow-up (40.6 [9.2] vs 39.5 [8.7]; P = .10). Sensitivity analysis stratified by BMI (≥40 vs <40) showed similar associations. Bariatric surgery was associated with greater weight loss, but GLP-1 RA therapy was associated with better outcomes. GLP-1 RA therapy in IIH is associated with significant reductions in medication use, symptoms/signs, and procedural interventions, suggesting its potential as a management strategy. Further prospective studies are warranted to confirm these findings.

Both glucagon-like peptide-1 receptor agonists (GLP-1 RA) and continuous glucose monitoring (CGM) improve glycemia in patients with type 2 diabetes (T2D). However, it is unknown whether adding CGM to GLP-1 RA therapy further improves A1c. We evaluated changes in A1c levels 6months after initiation of FreeStyle Libre (FSL) in adults with sub-optimally controlled T2D already on GLP-1 RA therapy. This retrospective, observational study used Optum's de-identified Market Clarity Data, a linked electronic health record-claims database to assess changes in A1c after FSL acquisition. Inclusion criteria were T2D diagnosis, ≥ 18years, baseline A1c ≥ 8%, with the first FSL acquisition between 2018 and 2022. Patients were required to be on GLP-1 RA prior to FSL with at least one GLP-1 RA prescription within 90days of FSL acquisition. GLP-1 RA initiation was defined as the earliest GLP-1 RA prescription from 2017 onwards. Paired changes in A1c were assessed at 6months after initial FSL acquisition. The study cohort included 1454 adults with T2D (age 55 ± 10years, 52% male, 38% with intensive insulin therapy, median 471days from GLP-1 RA initiation to FSL, and baseline A1c 9.8 ± 1.5%). After FSL acquisition, patients experienced an A1c decrease of 1.5 ± 1.9% (p < 0.001). Patients with a baseline A1c > 10% had the largest reduction (n = 497, - 2.7 ± 2.2%, p < 0.001). Significant improvements were observed in subgroups based on insulin therapy and GLP-1 RA formulation. Those initiating GLP-1 RA therapy > 24months before FSL acquisition also showed improvements in A1c (n = 478; - 1.3 ± 1.7%, p < 0.001). In a large, real-world study of adults with T2D, those on prior GLP-1 RA therapy experienced significant A1c improvements after acquiring FSL, irrespective of GLP-1 RA duration, GLP-1 RA formulation, or insulin therapy type. These findings support the use of FSL in adults with T2D treated with GLP-1 RA.

Strategies for weight management in older adults remain controversial as overweight may protect them against mortality whereas weight loss may have harmful effects by promoting sarcopenia and bone loss. It has been suggested that weight management for obese older adults should focus more on maintaining weight and improving physical function than promoting weight loss. This review aims to specify whether intentional weight loss in older adults is a useful or a wasting disease generating strategy. Recent randomized controlled studies have shown that a supervised, moderate caloric restriction coupled with regular exercise (both aerobic and resistance) in obese older adults do not increase mortality risk and may conversely reduce insulin resistance, metabolic complications, and disabilities without exacerbating lean mass and bone mineral density loss. In obese older adults, moderate weight loss may have beneficial effects on comorbidities, functional performances, and quality of life provided that regular physical activity can be associated. An individual approach considering life expectancy, chronic comorbidities, functional status, personal motivation, and social support should be preferred. More research is needed to define the circumstances in which cautious dietary restrictions are reasonably justified in older adults. In any case, in the oldest (≥80 years) as in frail individuals, it seems reasonable to abstain from recommending weight loss.

Studying long-term changes in neighborhood socioeconomic status (SES) may help to better understand the associations between neighborhood exposure and weight outcomes and provide evidence supporting neighborhood interventions. Little previous research has been done to examine associations between neighborhood SES and weight loss, a risk factor associated with poor health outcomes in the older population. To determine whether improvements in neighborhood SES are associated with reduced likelihoods of excessive weight gain and excessive weight loss and whether declines are associated with increased likelihoods of these weight outcomes. This cohort study was conducted using data from the National Institutes of Health-AARP (formerly known as the American Association of Retired Persons) Diet and Health study (1995-2006). The analysis included a cohort of 126 179 adults (aged 50-71 years) whose neighborhoods at baseline (1995-1996) were the same as at follow-up (2004-2006). All analyses were performed from December 2018 through December 2020. Living in a neighborhood that experienced 1 of 8 neighborhood SES trajectories defined based on a national neighborhood SES index created using data from the US Census and American Community Survey. The 8 trajectory groups, in which high, or H, indicated rankings at or above the sample median of a specific year and low, or L, indicated rankings below the median, were HHH (ie, high in 1990 to high in 2000 to high in 2010), or stable high; HLL, or early decline; HHL, or late decline; HLH, or transient decline; LLL, or stable low; LHH, or early improvement; LLH, or late improvement; and LHL, or transient improvement. Excessive weight gain and loss were defined as gaining or losing 10% or more of baseline weight. Among 126 179 adults, 76 225 (60.4%) were men and the mean (SD) age was 62.1 (5.3) years. Improvements in neighborhood SES were associated with lower likelihoods of excessive weight gain and weight loss over follow-up, while declines in neighborhood SES were associated with higher likelihoods of excessive weight gain and weight loss. Compared with the stable low group, the risk was significantly reduced for excessive weight gain in the early improvement group (odds ratio [OR], 0.87; 95% CI, 0.79-0.95) and for excessive weight loss in the late improvement group (OR, 0.89; 95% CI, 0.80-1.00). Compared with the stable high group, the risk of excessive weight gain was significantly increased for the early decline group (OR, 1.19; 95% CI, 1.08-1.31) and late decline group (OR, 1.13; 95% CI, 1.04-1.24) and for excessive weight loss in the early decline group (OR, 1.15; 95% CI, 1.02-1.28). The increases in likelihood were greater when the improvement or decline in neighborhood SES occurred early in the study period (ie, 1990-2000) and was substantiated throughout the follow-up (ie, the early decline and early improvement groups). Overall, we found a linear association between changes in neighborhood SES and weight outcomes, in which every 5 percentile decline in neighborhood SES was associated with a 1.2% to 2.4% increase in the risk of excessive weight gain or loss (excessive weight gain: OR, 1.01; 95% CI, 1.00-1.02 for women; OR, 1.02; 95% CI, 1.01-1.03 for men; excessive weight loss: OR, 1.02; 95% CI, 1.01-1.03 for women; OR, 1.02; 95% CI, 1.01-1.03 for men; P for- trend < .0001). These findings suggest that changing neighborhood environment was associated with changes in weight status in older adults.