GLP-1RA Use Research Articles

Glucagon-like peptide-1 receptor agonists use and associations with outcomes in heart failure and type 2 diabetes: data from the Swedish Heart Failure and Swedish National Diabetes Registries.

To assess the use and associations with outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RA) in a real-world population with heart failure (HF) and type 2 diabetes mellitus (T2DM). The Swedish HF Registry was linked with the National Diabetes Registry and other national registries. Independent predictors of GLP-1 RA use were assessed by multivariable logistic regressions and associations with outcomes were assessed by Cox regressions in a 1:1 propensity score-matched cohort. Of 8188 patients enrolled in 2017-21, 9% received a GLP-1 RA. Independent predictors of GLP-1 RA use were age <75 years, worse glycaemic control, impaired renal function, obesity, and reduced ejection fraction (EF). GLP-1 RA use was not significantly associated with a composite of HF hospitalization (HHF) or cardiovascular (CV) death regardless of EF, but was associated with a lower risk of major adverse CV events (CV death, non-fatal stroke/transient ischaemic attack, or myocardial infarction), and CV and all-cause death. In patients with body mass index ≥30 kg/m2, GLP-1 RA use was also associated with a lower risk of HHF/CV death and HHF alone. In patients with HF and T2DM, GLP-1 RA use was independently associated with more severe T2DM, reduced EF, and obesity and was not associated with a higher risk of HHF/CV death but with longer survival and less major CV adverse events. An association with lower HHF/CV death and HHF was observed in obese patients. Our findings provide new insights into GLP-1 RA use and its safety in HF and T2DM.

Glucagon-like Peptide-1 analogues and delipidation of coronary atheroma in statin-treated type 2 diabetic patients with coronary artery disease: The prespecified sub-analysis of the OPTIMAL randomized clinical trial

Background and aimsRandomized clinical trials have demonstrated the ability of glucagon-like peptide-1 analogues (GLP-1RAs) to reduce atherosclerotic cardiovascular disease events in patients with type 2 diabetes (T2D). How GLP-1RAs modulate diabetic atherosclerosis remains to be determined yet. MethodsThe OPTIMAL study was a prospective randomized controlled study to compare the efficacy of 48-week continuous glucose monitoring- and HbA1c-guided glycemic control on near infrared spectroscopty (NIRS)/intravascular ultrasound (IVUS)-derived plaque measures in 94 statin-treated patients with T2D (jRCT1052180152, UMIN000036721). Of these, 78 patients with evaluable serial NIRS/IVUS images were analyzed to compare plaque measures between those treated with (n = 16) and without GLP-1RAs (n = 72). ResultsAll patients received a statin, and on-treatment LDL-C levels were similar between the groups (66.9 ± 11.6 vs. 68.1 ± 23.2 mg/dL, p = 0.84). Patients receiving GLP-1RAs demonstrated a greater reduction of HbA1c [-1.0 (-1.4 to −0.5) vs. −0.4 (-0.6 to −0.2)%, p = 0.02] and were less likely to demonstrate a glucose level >180 mg/dL [-7.5 (-14.9 to −0.1) vs. 1.1 (-2.0 - 4.2)%, p = 0.04], accompanied by a significant decrease in remnant cholesterol levels [-3.8 (-6.3 to −1.3) vs. −0.1 (-0.8 - 1.1)mg/dL, p = 0.008]. On NIRS/IVUS imaging analysis, the change in percent atheroma volume did not differ between the groups (−0.9 ± 0.25 vs. −0.2 ± 0.2%, p = 0.23). However, GLP-1RA treated patients demonstrated a greater frequency of maxLCBI4mm regression (85.6 ± 0.1 vs. 42.0 ± 0.6%, p = 0.01). Multivariate analysis demonstrated that the GLP-1RA use was independently associated with maxLCBI4mm regression (odds ratio = 4.41, 95%CI = 1.19–16.30, p = 0.02). ConclusionsIn statin-treated patients with T2D and CAD, GLP-1RAs produced favourable changes in lipidic plaque materials, consistent with its stabilization.

Effects of glucagon-like peptide-1 receptor agonists on upper endoscopy in diabetic and nondiabetic patients

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) promote weight loss by suppressing appetite, enhancing satiety, regulating glucose metabolism, and delaying gastric motility. We sought to determine whether GLP-1 RA use could affect medical procedures such as EGD. We conducted a retrospective study of 35,183 patients who underwent EGD between 2019 and 2023, 922 of whom were using a GLP-1 RAs. Data were collected regarding demographics, diabetes status, retained gastric contents during EGD, incidence of aborted EGD, and necessity for repeat EGD. GLP-1 RA use was associated with a 4-fold increase in the retention of gastric contents (P< .0001), 4-fold higher rates of aborted EGD (P< .0001), and twice the likelihood of requiring repeat EGD (P= .0001), even after stratifying for the presence of diabetes. GLP-1 RA use can lead to delayed gastric emptying, affecting EGD adequacy regardless of the presence of diabetes, and may warrant dose adjustment to improve the safety and efficacy of these procedures.

The effect of GLP-1 receptor agonist use on negative evaluations of women with higher and lower body weight.

GLP-1 receptor agonists (GLP-1 RAs) have dramatically altered obesity treatment. Media reports suggest that GLP-1 RAs users often report feeling judged for taking a "shortcut" to lose weight, which may be related to negative stereotypes toward people with larger bodies. Media reports also describe negative attitudes about lean people who take GLP-1 RAs to enhance their appearance. The present research used a 2 × 2 experimental design to test the effects of GLP-1 RA use and body size on attitudes and egocentric impressions. A sample of 357 U.S. adults (Mage = 37.8, SD = 13) were randomly assigned to read about a woman, who either was lean or had obesity, and who lost 15% of her body weight either with diet/exercise or a GLP-1 RA. Participants answered questions measuring endorsement of negative weight-related stereotypes and egocentric attitudes toward the woman, as well as beliefs that she took a shortcut to lose weight and beliefs that biogenetic factors caused her baseline weight. Negative evaluations and egocentric impressions were stronger toward a woman who lost weight with a GLP-1 RA compared to diet/exercise. Losing weight with a GLP-1 RA led to stronger negative evaluations through higher weight loss shortcut beliefs irrespective of body size. Losing weight with a GLP-1 RA also led to higher egocentric impressions through higher shortcut beliefs, and this effect was stronger for a lean woman. Finally, losing weight with a GLP-1 RA led to more negative evaluations through stronger endorsement of biogenetic causal beliefs for a lean woman only. This timely study provides evidence that people with larger and smaller bodies alike are at-risk for being judged for using GLP-1 RAs due to beliefs that these medications are a shortcut. Findings also demonstrate novel reactions related to egotism when weight loss is achieved with pharmacological interventions. PRE-REGISTRATION AND DATA: osf.io/xme4w.

Association of Premorbid GLP-1RA and SGLT-2i Prescription Alone and in Combination with COVID-19 Severity.

People with type 2 diabetes are at heightened risk for severe outcomes related to COVID-19 infection, including hospitalization, intensive care unit admission, and mortality. This study was designed to examine the impact of premorbid use of glucagon-like peptide-1 receptor agonist (GLP-1RA) monotherapy, sodium-glucose cotransporter-2 inhibitor (SGLT-2i) monotherapy, and concomitant GLP1-RA/SGLT-2i therapy on the severity of outcomes in individuals with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Utilizing observational data from the National COVID Cohort Collaborative through September 2022, we compared outcomes in 78,806 individuals with a prescription of GLP-1RA and SGLT-2i versus a prescription of dipeptidyl peptidase 4 inhibitors (DPP-4i) within 24months of a positive SARS-CoV-2 PCR test. We also compared concomitant GLP-1RA/SGLT-2i therapy to GLP-1RA and SGLT-2i monotherapy. The primary outcome was 60-day mortality, measured from the positive test date. Secondary outcomes included emergency room (ER) visits, hospitalization, and mechanical ventilation within 14days. Using a super learner approach and accounting for baseline characteristics, associations were quantified with odds ratios (OR) estimated with targeted maximum likelihood estimation (TMLE). Use of GLP-1RA (OR 0.64, 95% confidence interval [CI] 0.56-0.72) and SGLT-2i (OR 0.62, 95% CI 0.57-0.68) were associated with lower odds of 60-day mortality compared to DPP-4i use. Additionally, the OR of ER visits and hospitalizations were similarly reduced with GLP1-RA and SGLT-2i use. Concomitant GLP-1RA/SGLT-2i use showed similar odds of 60-day mortality when compared to GLP-1RA or SGLT-2i use alone (OR 0.92, 95% CI 0.81-1.05 and OR 0.88, 95% CI 0.76-1.01, respectively). However, lower OR of all secondary outcomes were associated with concomitant GLP-1RA/SGLT-2i use when compared to SGLT-2i use alone. Among adults who tested positive for SARS-CoV-2, premorbid use of either GLP-1RA or SGLT-2i is associated with lower odds of mortality compared to DPP-4i. Furthermore, concomitant use of GLP-1RA and SGLT-2i is linked to lower odds of other severe COVID-19 outcomes, including ER visits, hospitalizations, and mechanical ventilation, compared to SGLT-2i use alone. Graphical abstract available for this article.

Glucagon-Like Peptide-1 Receptor Agonists and Thyroid Cancer: A Narrative Review.

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are highly effective medications for the treatment of type 2 diabetes and obesity. Pharmacological studies in rodents support an association between the use of GLP-1 RAs and the development of medullary thyroid cancer (MTC) resulting in a black box warning for these agents in patients at risk for this condition. Yet, the association between GLP-1 RAs and non-MTC remains controversial. Excessive worry about unproven thyroid cancer risk might lead to underutilizing GLP-1 RAs in patients who could otherwise experience substantial benefits. Unwarranted concerns about thyroid cancer could lead to unnecessary thyroid cancer screening and harms from overdiagnosis. Summary: The body of evidence assessing the association between GLP-1 RA use and thyroid cancer spans a wide range of methodologies, including basic and translational research investigating biological plausibility; randomized trials assessing clinical efficacy and providing the strongest evidence for causality; observational studies providing real-life outcome evaluation in larger populations but with limited evaluation of covariates or dependable outcome definitions; and pharmacovigilance studies that provide postmarketing assessments of a safety signal but do not address causality. There is biological plausibility supporting an association between GLP-1 RA and MTC in rodents, which is less clear for non-MTC in humans. Clinical evidence from randomized trials and associated meta-analysis suggest thyroid cancer as a rare event making effect estimates imprecise but without conclusive and consistent evidence of increase risk in those receiving GLP-1 RA. Observational studies at higher risk of bias also show low event rates for thyroid cancer, with effect estimates that are inconsistent among different studies. Pharmacovigilance studies consistently show a signal of increased reporting of thyroid cancer in patients treated with GLP-1 RA. Conclusions: Evidence from randomized controlled trials indicates occurrence of thyroid cancer is infrequent in individuals exposed to GLP-1 RA. Observational studies at higher risk of bias yield inconsistent results. Overall there is no conclusive evidence of elevated thyroid cancer risk. These findings can help clinicians when addressing patient's concerns about a potential yet unproven link between GLP-1 RA therapy and thyroid cancer.

Glucagon-Like Peptide-1 Receptor Agonist Use and Residual Gastric Content Before Anesthesia

Glucagon-like peptide-1 receptor agonist (GLP-1 RA) use is rapidly increasing in the US, driven by its expanded approval for weight management in addition to hyperglycemia management in patients with type 2 diabetes. The perioperative safety of these medications, particularly with aspiration risk under anesthesia, is uncertain. To assess the association between GLP-1 RA use and prevalence of increased residual gastric content (RGC), a major risk factor for aspiration under anesthesia, using gastric ultrasonography. This cross-sectional study prospectively enrolled patients from a large, tertiary, university-affiliated hospital from June 6 through July 12, 2023. Participants followed preprocedural fasting guidelines before an elective procedure under anesthesia. Patients with altered gastric anatomy (eg, from previous gastric surgery), pregnancy, recent trauma (<1 month), or an inability to lie in the right lateral decubitus position for gastric ultrasonography were excluded. Use of a once-weekly GLP-1 RA. The primary outcome was the presence of increased RGC, defined by the presence of solids, thick liquids, or more than 1.5 mL/kg of clear liquids on gastric ultrasonography. Analysis was adjusted for confounders using augmented inverse probability of treatment weighting, a propensity score-based technique. Secondarily, the association between the duration of drug interruption and the prevalence of increased RGC was explored. Among the 124 participants (median age, 56 years [IQR, 46-65 years]; 75 [60%] female), the prevalence of increased RGC was 56% (35 of 62) in patients with GLP-1 RA use (exposure group) compared with 19% (12 of 62) in patients who were not taking a GLP-1 RA drug (control group). After adjustment for confounding, GLP-1 RA use was associated with a 30.5% (95% CI, 9.9%-51.2%) higher prevalence of increased RGC (adjusted prevalence ratio, 2.48; 95% CI, 1.23-4.97). There was no association between the duration of GLP-1 RA interruption and the prevalence of increased RGC (adjusted odds ratio, 0.86; 95% CI, 0.65-1.14). Use of a GLP-1 RA was independently associated with increased RGC on preprocedural gastric ultrasonography. The findings suggest that the preprocedural fasting duration suggested by current guidelines may be inadequate in this group of patients at increased risk of aspiration under anesthesia.

Relationship between Glucagon-like Peptide-1 Receptor Agonists and Cardiovascular Disease in Chronic Respiratory Disease and Diabetes.

The purpose of this paper is to assess the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on stroke or heart disease in patients having chronic respiratory disease and diabetes (CD) with underlying diseases related to COVID-19. From 1998 to 2019, we adjusted competing risk by assessing the effect of GLP-1RAs on stroke or heart disease in a CD cohort after propensity matching based on the Taiwan National Health Insurance Research Database. We also used the time-dependent method to examine the results. GLP-1 RA and non-GLP-1 RA user groups included 15,801 patients (53% women and 46% men with a mean age of 52.6 ± 12.8 years). The time between the diagnoses of DM and the initial use of the GLP-1 RA among the stroke subcohort (<2000 days) was shorter than that of the heart disease subcohort (>2000 days) (all p-values < 0.05). The overall risks of stroke, ischemic, and hemorrhagic stroke were significantly lower in GLP-1 RA users than nonusers. The adjusted subhazard ratio (aSHR) was 0.76 [95% CI 0.65-0.90], 0.77 [95% CI 0.64-0.92], and 0.69 [95% CI 0.54-0.88] (p < 0.05 for all). Furthermore, a ≥351-day use had a significantly lower stroke risk than GLP-1 RA nonusers (aSHR 0.35 [95% CI 0.26-0.49]). The time-dependent method revealed the same result, such as lower stroke, and ischemic or hemorrhagic stroke risk. In contrast, the cardiac arrhythmia incidence was higher in GLP-1 RA users with an aSHR of 1.36 [95% CI 1.16-1.59]. However, this risk disappeared after the ≥351-day use with 1.21 (0.98, 1.68) aSHR. Longer GLP-1 RA use was associated with a decreased risk of ischemic or hemorrhagic stroke and the risk of cardiac arrhythmia disappears in a CD cohort. Both a shorter lag time use of the GLP-1 RA and a longer time use of GLP-1 RA were associated with a decreased risk of ischemic or hemorrhagic stroke in the CD cohort. The GLP-1 RA use in the early stage and optimal time use in the CD cohort may avoid the stroke risk.

Sodium-Glucose Cotransporter 2 Inhibitors Reduce the Risk of Hospitalization for Heart Failure and Amputation Rate Compared With Incretin-Based Therapy in Patients With Diabetic Foot Disease: A Nationwide Population-Based Study

ObjectiveMajor adverse cardiovascular event (MACE) outcomes associated with sodium-glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapies remain unclear in patients with type 2 diabetes and newly diagnosed diabetic foot complications (DFCs). This study examined the impact of SGLT2i and GLP-1 RA use on the rates of MACEs and amputations in patients with type 2 diabetes and without cardiovascular disease. MethodsData from the Taiwan National Health Insurance Research Database (2004-2017) were analyzed, focusing on patients with type 2 diabetes without previous MACE and newly diagnosed DFCs. The primary outcome was the first MACE occurrence, and the secondary outcomes included MACE components, all-cause mortality, and lower extremity amputation (LEA) rates. ResultsSGLT2i users showed a significant decrease in the MACE (hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.46-0.88) and hospitalization for heart failure (HR, 0.54; 95% CI, 0.35-0.83) rates compared with dipeptidyl peptidase-4 inhibitor users. The amputation rates were also lower in SGLT2i users without LEA at the first DFC diagnosis (HR, 0.28; 95% CI, 0.10-0.75) and did not increase in those with a history of peripheral artery disease or LEA. No significant differences were observed between dipeptidyl peptidase-4 inhibitor and GLP-1 RA users in terms of the primary or secondary outcomes. ConclusionIn patients with type 2 diabetes initially diagnosed with DFC, SGLT2i are effective in significantly reducing the hospitalization for heart failure and MACE rates. SGLT2i lower the amputation rates, especially in patients who have not previously had a LEA, than the dipeptidyl peptidase-4 inhibitor therapy.

Abstract WP278: Trends in GLP1RA and SGLT2i Use in Ischemic Stroke Patients With Diabetes

Background: The current AHA stroke prevention guidelines give Class 1 recommendations that patients with AIS and diabetes should receive glucose-lowering agents with cardiovascular benefit to reduce risk of MACE. The ADA recommends in patients with ASCVD, when prevention of further vascular events is the priority, a GLP1RA should be added; and when concern for heart failure or chronic kidney disease is the priority, a SGLT2i should be added. Objective: Among a cohort of patients with diabetes presenting with AIS, we analyzed rates of GLP1RA and SGLT2i use during hospitalization and/or outpatient follow-up. Methods: A retrospective review of AIS patients at a comprehensive stroke center between May 2016 and October 2022 was conducted using an institutional registry. Patients were identified to have diabetes as derived by the Charlson Comorbidity Index ICD 10 codes E10 through E14. We then identified patients receiving GLP1RA or SGLT2i and evaluated trends over time. Results: 4131 patients were identified of which 2045 (49.4%) had a diagnosis of diabetes. Of these patients 60/2045 (2.9%) were on GLP1RA while 35/2045 (1.7%) were on SGTLi for total of 4.6%. Annual trends were 2016 6/220 (2.7%) and 1/220 (0.4%), in 2017 6/347 (1.7%) and 3/347 (0.8%), in 2018 6/377 (1.6%) and 5/377 (1.3%), in 2019 3/240 (1.2%) and 1/240 (0.4%), in 2020 9/335 (2.7%) and 10/335 (3.0%), in 2021 11/322 (3.4%) and 10/322 (3.1%), in 2022 19/205 (9.2%) and 5/205 (2.4%) for GLP1RA and SGLT2i, respectively. Conclusions: In this retrospective analysis of 4131 AIS cases, use of GLP1RA and SGLT2i prior to 2019 remained around 2-3%. Following publication of the 2021 stroke prevention guidelines, GLP1RA use increased in 2022 to 9%. However, the study highlights the still-low rates of use of secondary MACE prevention despite Class 1 recommendations. This analysis serves as a call to attention that improving treatment of diabetes with ASCVD risk-reduction is a potential area of improvement.

Abstract TP51: Improving Prescriptions of Cardiovascular-Effective Anti-Diabetic Medications in Patients With Stroke and Type 2 Diabetes

Background and Issue: Type 2 diabetes (DM2) and cardiovascular (CV) disease pose significant risks for ischemic stroke, with a heightened impact on marginalized and under-resourced communities. Despite known CV benefits of newer anti-diabetic medications like glucagonlike peptide 1 receptor agonists (GLP-1 RA) and sodium-glucose co-transporter-2 (SGLT2) inhibitors, these medications are under prescribed. To improve utilization, we conducted a quality improvement (QI) project to enhance prescription rates for these medications. The QI initiative focused on improving diabetes education and ensuring appropriate hypoglycemic medications were provided at discharge, with an aim of reducing the incidence of recurrent strokes. Purpose: The goal of this QI initiative was to improve prescription rates of GLP-1 R or SGLT2 inhibitors in eligible patients with stroke. Method: An assessment of current diabetic referral practices and medical therapy management were conducted, and an algorithm aimed at streamlining referrals for diabetic consults for patients with stroke developed. A diabetic educator or advanced practice nurse was consulted for patients with stroke and elevated A1c. Patients were then evaluated for qualification and use of GLP-1 RA or SGLT2 inhibitors, and discharge recommendations provided. A stroke registry was used to conduct a retrospective analysis of cases with stroke and DM2 for discharged prescriptions of GLP-1 R or SGLT2 inhibitors. Pre-implementation data from October 2021 to March 2022 were compared to post-implementation data from October 2022 to March 2023. Results: A review of 273 cases was completed. Prior to the QI implementation, 14.2% (19 of 134) of cases admitted for stroke with a secondary diagnosis of DM2 and elevated A1c were discharged home on a GLP-1 RA or SGLT2 inhibitor compared with 28.8% (40 of 139) of cases post implementation. Conclusion: Implementation of a QI process aimed at increasing the number of written discharge prescriptions for DM2 medications with proven CV benefits demonstrated a substantial increase in the number of written prescriptions for these medications at discharge.

Effects of glucagon-like peptide-1 receptor agonists on liver-related and cardiovascular mortality in patients with type 2 diabetes

BackgroundPatients with type 2 diabetes (T2D) tend to have nonalcoholic fatty liver disease (NAFLD) with poorer prognosis. We performed this research to compare the risks of cardiovascular diseases, cirrhosis, liver-related mortality, and cardiovascular mortality between glucagon-like peptide-1 receptor agonist (GLP-1 RA) use and no-use in patients with T2D without viral hepatitis.MethodsFrom January 1, 2008, to December 31, 2018, we used propensity-score matching to identify 31,183 pairs of GLP-1 RA users and nonusers from Taiwan’s National Health Insurance Research Database. Multivariable-adjusted Cox proportional hazards models were used to examine the outcomes between the study and control groups.ResultsThe median (Q1, Q3) follow-up time for GLP-1 RA users and nonusers were 2.19 (1.35, 3.52) and 2.14 (1.19, 3.68) years, respectively. The all-cause mortality incidence rate was 5.67 and 13.06 per 1000 person-years for GLP-1 RA users and nonusers, respectively. Multivariable-adjusted analysis showed that GLP-1 RA use had significantly lower risks of all-cause mortality (aHR 0.48, 95%CI 0.43–0.53), cardiovascular events (aHR 0.92, 95%CI 0.86–0.99), cardiovascular death (aHR 0.57, 95%CI 0.45–0.72), and liver-related death (aHR 0.32, 95%CI 0.13–0.75). However, there was no significant difference in the risk of liver cirrhosis development, hepatic failure, and hepatocellular carcinoma compared to GLP-1 RA no-use.ConclusionsThis nationwide cohort study showed that GLP-1 RA use was associated with a significantly lower risk of all-cause mortality, cardiovascular events, and cardiovascular death in patients with T2D among Taiwan population. More prospective studies are warranted to verify our results.

In-Home Management of Diabetes and Obesity.

The prevalence of type 2 diabetes and obesity is increasing. Research has demonstrated the use of GLP-1 RA and SGLT-2i medications to be safe and effective for the long-term management of T2DM and obesity. As continued research supports the use of GLP-1 RA and SGLT-2i medications for additional indications, home care clinicians will increasingly care for patients on these medications. It is imperative that home care clinicians are aware of patient indications, adverse effects, and potential safety considerations related to these drugs to ensure patient goals are met.

Comparison of GLP-1 Receptor Agonists, SGLT-2 Inhibitors, and DPP-4 Inhibitors as an Add-On Drug to Insulin Combined With Oral Hypoglycemic Drugs: Umbrella Review.

Background: The objective was to evaluate the efficacy of the combination of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase-4 inhibitors (DPP-4i), and sodium-glucose cotransporter 2 inhibitor (SGLT-2i) in the treatment of Type 2 diabetes with poor efficacy of basic insulin and metformin/sulfonylurea by umbrella review. Materials and Methods: Forming the data of publication of each database through 13 September 2022, PubMed, EMBASE, and Cochrane Library were surveyed. Results: A total of seven meta-analyses were included in the umbrella review. The combination of GLP-1 RA (WMD -3.41 [-5.61, -1.21], p = 0.002), SGLT-2i (WMD -5.34 [-9.56, -1.13], p = 0.013), and DPP-4i (WMD -5.56 [-7.39, -3.73], p ≤ 0.001) can significantly reduce HbA1c levels, respectively. The combination of GLP-1 RA (WMD -1.55 [-2.92, -0.18], p = 0.027), SGLT-2i (WMD -2.96 [-6.68, 0.77], p = 0.12), and DPP-4i (WMD -2.05 [-2.82, -1.28], p ≤ 0.001) can significantly reduce fasting plasma glucose (FPG) levels, respectively. The combination of GLP-1 RA (WMD -3.24 [-5.14, -1.34], p < 0.001) can significantly reduce body weight of Type 2 diabetes mellitus (T2DM). The dose of basic insulin in diabetes patients after combined use of GLP-1 RA (WMD -2.74 [-4.26, -1.22], p ≤ 0.001) was significantly reduced. The combination use of GLP-1 RAs (OR 1.28 [1.05, 1.56], p = 0.017) increases the risk of hypoglycemia. Conclusions: The combination of GLP-1 RAs, DPP-4i, and SGLT-2i can effectively lower HbA1c and FPG in T2DM patients who have poor therapeutic effects on basic insulin combined with metformin/sulfonylureas, respectively. Compared to placebo, GLP-1 RAs can significantly reduce body weight and basic insulin dosage, while DPP-4i and SGLT-2i have a lower risk of hypoglycemia. Trial Registration: CRD42023410345.

Impact of GLP-1 Agonists on Male Reproductive Health-A Narrative Review.

Background and objective-Obesity is a prevalent health concern that notably impairs male fertility through hormonal disruptions and other pathophysiological alterations. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can significantly reduce weight. This narrative review synthesizes the existing literature discussing the impact of glucagon-like peptide-GLP-1 RAs on the male reproductive system, particularly on the hypothalamic-pituitary-gonadal axis and spermatogenesis, highlighting their potential impact on male fertility. Material and methods-PubMed database was used for the retrieval of English-language articles published up to November 2023. This non-systematic literature review predominantly concentrates on both pre-clinical and clinical studies pertaining to GLP-1 RAs, specifically exploring their impact on male reproductive hormones and sperm parameters. Results-GLP-1 receptors have been identified within the male reproductive system according to the existing literature. While the exact mechanisms are not well understood, they appear to be involved in glucose homeostasis and energy metabolism, both vital processes in spermatogenesis. Multiple clinical trials have demonstrated the efficacy of GLP-1 RAs for promoting weight loss. Recent studies show that the use of GLP-1 RAs in obese males may enhance sperm metabolism, motility, and insulin secretion in vitro, along with positive effects on the human Sertoli cells. Recent clinical trials discussed in this review demonstrate weight loss associated with GLP-1 RAs is correlated with improvements in sperm count, concentration, and motility. However, the direct impact of GLP-1 RAs on male reproductive hormones remains unclear, necessitating further research to confirm their potential role in treating male infertility. Conclusions-This narrative review summarizes the existing literature discussing the potential impact of GLP-1 RA on the male reproductive system, emphasizing their potential therapeutic role in addressing idiopathic infertility in obese men. Despite numerous studies exploring the influence of GLP-1 and GLP-1 RAs on reproductive hormones, testicular function, and spermatogenesis, further clinical trials are crucial to validate initial evidence. Longer follow-up periods are essential to address uncertainties regarding the long-term repercussions and outcomes of GLP-1 RA use. While this holds true, the current literature suggests that GLP-1RAs show promise as a potential therapeutic approach for improving sperm parameters in obese men.

Second-year results from CINEMA: A novel, patient-centered, team-based intervention for patients with Type 2 diabetes or prediabetes at high cardiovascular risk

BackgroundThe care for patients with type 2 diabetes mellitus (T2DM) necessitates a multidisciplinary team approach to reduce cardiovascular (CV) risk but implementation of effective integrated strategies has been limited. Methods and ResultsWe report 2-year results from a patient-centered, team-based intervention called CINEMA at University Hospitals Cleveland Medical Center. Patients with T2DM or prediabetes at high-risk for CV events, including those with established atherosclerotic CVD, elevated coronary artery calcium score ≥100, chronic heart failure with reduced ejection fraction, chronic kidney disease (CKD) stages 2–4, and/or prevalent metabolic syndrome were included. From May 2020 through September 2022, 426 patients were enrolled in the CINEMA program. A total of 227 (54%) completed ≥1 follow-up visit after an initial baseline visit with median (IQR) follow-up time 4 [3–7] months with maximum follow-up time 19 months. Mean age was 60 years, 47 % were women, and 37 % were Black and 85% had prevalent T2DM, 48 % had established ASCVD, 29% had chronic HF, 27% had CKD and mean baseline 10-year ASCVD risk estimate was 25.1 %; baseline use of a SGLT2i or GLP-1RA was 21 % and 18 %, respectively. Patients had significant reductions from baseline in body weight (-5.5 lbs), body mass index (-0.9 kg/m2), systolic (-3.6 mmHg) and diastolic (-1.2 mmHg) blood pressure, Hb A1c (-0.5 %), total (-10.7 mg/dL) and low-density lipoprotein (-9.0 mg/dL) cholesterol, and triglycerides (-13.5 mg/dL) (p<0.05 for all). Absolute 10-year predicted ASCVD risk decreased by ∼2.4 % (p<0.001) with the intervention. In addition, rates of guideline-directed cardiometabolic medication prescriptions significantly increased during follow-up with the most substantive changes seen in rates of SGLT2i and GLP-1RA use which approximately tripled from baseline (21 % to 57 % for SGLT2i and 18 % to 65 % for GLP-1RA, p<0.001 for both). ConclusionsThe CINEMA program, an integrated, patient-centered, team-based intervention for patients with T2DM or prediabetes at high risk for cardiovascular disease has continued to demonstrate effectiveness with significant improvements in ASCVD risk factors and improved use of evidence-based therapies. Successful implementation and dissemination of this care delivery paradigm remains a key priority.

1982. GLP-1 Receptor Agonists Promote Weight Loss Among People with HIV

Abstract 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

Glucagon-like peptide-1 receptor agonist and sodium-glucose cotransporter 2 inhibitor use among adults with diabetes mellitus by cardiovascular-kidney disease risk: National Health and Nutrition Examination Surveys, 2015–2020

ObjectiveGlucagon-like peptide-1 receptor agonists (GLP1-RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2Is) lower adverse cardiac and kidney events among high-risk patients with diabetes mellitus (DM) and are now guideline-recommended as first-line therapy alongside metformin. However, the adoption of these new treatments from 2015 to 2020 among the highest-risk adults with DM remains unclear. MethodsWe performed a cross-sectional analysis of the National Health and Nutrition Examination Surveys (NHANES) 2015–2020 to estimate the use of GLP1-RAs and SGLT2Is among adults with DM overall and by level of cardiovascular and kidney risk (CKR). We defined high CKR by history of atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), heart failure, or age ≥55 years with at least 2 ASCVD risk factors (i.e., obesity, hypertension, hyperlipidemia, or current smoker). ResultsOverall, 2,432 participants with DM (mean age 60.6 years, 46.8 % female, 58.8 % Non-Hispanic White) were included, of which 1,869 and 563 were with and without high CKR, respectively. Participants with vs. without high CKR were more likely to be older, have higher systolic blood pressure, lower estimated glomerular filtration rate, use oral antidiabetic agents, and have health insurance. Overall, the weighted prevalence of GLP1-RA or SGLT2I was 9.0 % (95 % confidence interval [CI] 6.9–11.0): 4.8 % (95 % CI 3.6–6.1) took GLP1-RAs, and 5.1 % (95 % CI 3.3–7.0) took SGLT2Is. Use of GLP1-RAs or SGLT2Is did not differ between participants with vs. without high CKR (adjusted prevalence ratio [aPR] 1.00; 95 % CI 0.98–1.02). Participants with ASCVD were more likely to be on a GLP1-RA or SGLT2I (aPR 1.28; 95 % CI 1.25–1.31), while adults with CKD were less likely (aPR 0.84; 95 % CI 0.82–0.86). ConclusionAmong US adults with DM, GLP1-RA and SGLT2I use was low regardless of CKR. Data since 2020 analyzing the utilization of GLP1-RAs and SGLT2Is among high-CKR patients with DM is needed to identify implementation strategies for increased utilization.

Trends and site-level variation of novel cardiovascular medication utilization among patients admitted for heart failure or coronary artery disease in the US Veterans Affairs System: 2017-2021

We assessed trends in novel cardiovascular medication utilization in US Veterans Affairs (VA) for angiotensin receptor-neprilysin inhibitors (ARNI), sodium-glucose cotransporter-2 Inhibitors (SGLT2i), and glucagon-like peptide-1 receptor agonists (GLP-1 RA). We retrospectively identified cohorts from 114 VA hospitals with admission for prevalent 1) systolic heart failure (HF, N=82,375) or 2) coronary artery disease and diabetes (CAD+T2D, N=74,209). Site-level data for prevalent filled prescriptions were assessed at hospital admission, discharge, or within 6 months of discharge. Variability among sites was estimated with median odds ratios (mOR), and within-site Pearson correlations of utilization of each medication class were calculated. Site- and patient-level characteristics were compared by high-, mixed-, and low-utilizing sites. ARNI and SGTL2i use for HF increased from <5% to 20% and 21%, respectively, while SGTL2i or GLP-1 RA use for CAD+T2D increased from <5% to 30% from 2017 to 2021. Adjusted mOR and 95% confidence intervals for ARNI, SGTL2i for HF, and SGTL2i or GLP-1 RA for CAD+T2D were 1.73 (1.64-1.91), 1.72 (1.59-1.81), and 1.53 (1.45-1.62), respectively. Utilization of each medication class correlated poorly with use of other novel classes (Pearson <0.38 for all). Higher patient volume, number of beds, and hospital complexity correlated with high-utilizing sites. Utilization of novel medications has increased over time but remains suboptimal for US Veterans with HF and CAD+T2D, with substantial site-level heterogeneity despite a universal medication formulary and low out-of-pocket costs for patients. Future work should include further characterization of hospital- and clinician-level practice patterns to serve as targets to increase implementation.

GLP1-RA versus metformin as first-line therapy for achieving glycemic control and risk-factor management - a one-year nationwide cohort study

Abstract Background Glucagon-like peptide 1 receptor agonist (GLP1-RA) reduces cardiovascular events in patients with long standing diabetes. We hypothesized that treatment early during diabetes could be beneficial. Purpose The aim was to compare one-year effects of GLP1-RA and metformin as first-line glucose-lowering therapy on glycemic control, adherence, kidney function, and cholesterol levels. Methods Using the Danish nationwide registers, we included all first-line users of monotherapy with GLP1-RA or metformin between 2018-2021, who had information on glycated hemoglobin (HbA1c) maximum one year prior to baseline and a measured HbA1c level above 41 mmol/mol. The outcomes were one-year change in HbA1c category, adherence to therapy, avoidance of add-on glucose lowering drugs, as well as absolute change in HbA1c, creatinine, and cholesterol levels. Targeted likelihood maximum estimation with ensemble Superlearning was used to estimate the average treatment effects. Results A total of 40,987 individuals were included, of which 870 were prescribed GLP1-RA and 40,117 were prescribed metformin. After adjusting for age, sex, income, education, degree of urbanization, baseline HbA1c levels, comorbidities, and concomitant medication, GLP1-RA users had an one-year absolute decrease in HbA1c (ATE: -3.84 mmol/mol, 95% CI: -5.36;.-2.33), and HDL (ATE: -0.03 mmol/L, 95% CI: -0.06;-0.01), an absolute increase in creatinine (ATE: 2.89 μmol/L, 95% CI: 0.07;4.82), and no difference in low-density lipoprotein cholesterol (ATE: 0.11 mmol/L [95% CI: -0.03;0.24]), total lipoprotein cholesterol (ATE: 0.13 mmol/L [95% CI: -0.03;0.29]), triglycerides (ATE: 0.02 mmol/L [95% CI: -0.25;0.30]), non-adherence (RR: 1.05 [95% CI: 0.75;1.46]), and add-on therapy (RR: 1.04 [95% CI: 0.75;1.44]), compared to metformin users. Conclusion First line use of GLP1-RA was associated with a clear one-year reduction of HbA1c and a very small increase in creatinine. Future studies are needed to show whether this translates to a clinical benefit.