Glucagon-like Peptide-1 Research Articles

Potential of GLP-1 Analogs in Managing Hyperphagia and Obesity in Prader-Willi Syndrome: A Review of Efficacy and Safety

Introduction: Prader-Willi Syndrome (PWS) is a genetic disorder marked by hyperphagia, obesity, developmental delays, and behavioral challenges. Traditional treatments like dietary control and growth hormone therapy often fail to effectively manage these symptoms. Recently, glucagon-like peptide-1 (GLP-1) analogs have shown potential in treating PWS. This review assesses the efficacy, safety and mechanisms of GLP-1 analogs in PWS treatment. They improve glycemic control, cardiovascular health, and appetite regulation, contributing to better weight management and overall health in PWS patients. These analogs enhance insulin secretion, inhibit glucagon release, and slow gastric emptying, helping to reduce postprandial glucose spikes and caloric intake. Results: Several small-scale studies and case reports have shown mixed results regarding the effectiveness of GLP-1 analogs in reducing BMI and hyperphagia in PWS patients. Although the studies demonstrated varied outcomes in terms of BMI reduction, all of them reported improvement in satiety or appetite levels.Conclusions: Overall, GLP-1 analogs hold promise for addressing hyperphagia, obesity, and glycemic control in PWS patients, improving their overall health and quality of life. Continued research and long-term studies are essential to establish these benefits and optimize treatment strategies.

Cardiomodulatory Effects of Cardiometabolic and Antihyperglycemic Medications: The Roles of Oxidative and Endoplasmic Reticulum Stress.

Uncontrolled hyperglycemia in people with diabetes is an established risk of premature cardiovascular disease. Repeated hypoglycemic events are also associated with increased cardiovascular mortality. Both hyperglycemia and hypoglycemia induce cellular stress, notably endoplasmic reticulum (ER) stress, a known promoter of cardiovascular disease. Contemporary anti-hyperglycemic drugs such as glucagon-like peptide 1 (GLP-1) receptor agonists and sodium-glucose cotransporter 2 (SGLT-2) inhibitors simultaneously inhibit oxidative stress and ER stress in human coronary artery endothelial cells. Similarly, other known cardioprotective drugs, such as statins and inhibitors of the renin-angiotensin-aldosterone system (RAAS) share a common pleiotropic effect of reducing cellular stress. Antioxidants reduce oxidative stress but may aggravate ER stress. This dichotomy of antioxidant effects may underline the unfavorable outcomes of clinical trials with antioxidant vitamin use. The aim of this review is to highlight the potential role of cellular stress reduction in cardioprotective effects of contemporary diabetes drugs. Future clinical trials are needed to test the hypothesis that cellular stress is the fundamental culprit in cardiovascular disease.

Obesity Nephropathy: A Current Overview

The obesity pandemic is a public health problem that is evolving at high speed with both functional and vital outcomes. Recently, many studies have shown that obesity is a driver of chronic kidney disease onset and progression. The mechanisms underlying this fact are multiple including inflammation, oxidative stress, insuline resistance and hemodynamic change with inappropriate RAAS and SNS activation; occuring on a particularly genetic basis of individual predisposition. In this field, Obesity-related glomerulopathy is characterized by glomerulomegaly with localized and segmental glomerulosclerosis lesions. Main symptoms are non specific, dominated by microproteinuria, rarely nephrotic syndrome and a slowed decline in glomerular filtration rate. As for treatment, it starts essentially with lifestyle interventions targeting a meaningful and sustainable weight loss, accompanied by antiobesity medications (AOMS) including RAAS blockers, SGLT2inhibitors and since very recently, long-acting glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RA) which were shown to be effective in managing weight loss in non-chronic kidney disease (CKD) patients. Preliminary results of more definitive studies in CKD patients are currently being finalized. Bariatric surgery could reduce the risk of mortality in obese CKD patients; it is recommended for patients with severe morbid obesity, poor tolerance to AOMS, particularly GLP RA, or those whose long-term medication costs represent a barrier to sustainable results. In this review, we summarize epidemiological data on obesity nephropathy, its pathophysiological mechanisms, clinical features and perspectives on its treatment.

Obesity Management in Youth with Duchenne Muscular Dystrophy: A Review of Metformin and Alternative Pharmacotherapies.

Background: Individuals with Duchenne muscular dystrophy (DMD) have increased risk of obesity from prolonged glucocorticoid use and progressive muscle weakness. Over 50% have obesity by the teenage years. Objectives: The current study examines literature on obesity management in DMD and describes how obesity pharmacotherapy can be used in this high-risk cohort. Methods: This review was conducted in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. A Pubmed Database search was conducted from January 2000 to May 2024. Included terms were DMD and topiramate, phentermine, metformin, glucagon-like peptide-1 receptor agonist, semaglutide, and liraglutide. Eligible studies were cataloged to examine obesity pharmacotherapy, side effect profiles, and clinical outcomes. Results: Twenty studies met inclusion criteria, 18 on metformin. Reviewed studies varied in duration from 4 to 24 weeks, ages 6.5-44 years old, with 112 participants total (range: 1-30 participants). Included studies were: eight animal studies, six clinical trials, four reviews, one cohort study, and one case report. Primary outcomes varied among studies: muscular degeneration and function (15 articles), cardiac function (2 articles), weight loss (2 articles), and general endocrine care (1 article). Conclusions: Adjunct obesity pharmacotherapy use in youth with DMD is promising but needs to be confirmed. Large gaps include appropriate agent selection, side effect monitoring, and dose escalation. The overall quality of pediatric-specific evidence for the use of obesity pharmacotherapy in youth with DMD is low. Future research is needed to investigate how to safely utilize these agents.

Effect of glucagon-like peptide-1 receptor agonists on prostate cancer: A review.

Glucagon-like peptide-1 receptor agonist (GLP-1RA) is widely used in the treatment of type 2 diabetes mellitus (T2DM) for its significant hypoglycemic effect, weight loss and small side effects. Some studies have shown that GLP-1RA has an inhibitory effect on prostate cancer, and its application will produce adverse effects associated with an increased or decreased risk of some tumors. GLP-1R is widely expressed by various types of cells and tissues in the human body, so GLP-1RA has attracted wide clinical attention to the occurrence, development and prognosis of tumors, which brings more new directions and hopes for the treatment of prostate cancer. This paper describes the expression of glucagon-like peptide-1 receptor (GLP-1R) in prostate cancer and the effects of glucagon-like peptide-1 receptor agonist (GLP-1RA) on prostate cancer.

Limited evidence for anatomical contacts between intestinal GLP-1 cells and vagal neurons in male mice

The communication between intestinal Glucagon like peptide 1 (GLP-1)-producing cells and the peripheral nervous system has garnered renewed interest considering the availability of anti-obesity and anti-diabetic approaches targeting GLP-1 signaling. While it is well-established that intestinal GLP-1 cells can exert influence through paracrine mechanisms, recent evidence suggests the possible existence of synaptic-like connections between GLP-1 cells and peripheral neurons, including those of the vagus nerve. In this study, using a reporter Phox2b-Cre-Tomato mouse model and super-resolution confocal microscopy, we demonstrated that vagal axons made apparent contacts with less than 0.5% of GLP-1 cells. Moreover, immunohistochemistry combined with super-resolution confocal microscopy revealed abundant post-synaptic density 95 (PSD-95) immunoreactivity within the enteric plexus of the lower intestines of C57/BL6 mice, with virtually none in its mucosa. Lastly, utilizing RNAScope in situ hybridization in the lower intestines of mice, we observed that GLP-1 cells expressed generic markers of secretory cells such as Snap25 and Nefm, but neither synaptic markers such as Syn1 and Nrxn2, nor glutamatergic markers such as Slc17a7. Through theoretical considerations and a critical review of the literature, we concluded that intestinal GLP-1 cells primarily communicate with vagal neurons through paracrine mechanisms, rather than synaptic-like contacts.

Hypoglycemic effects of white hyacinth bean polysaccharide on type 2 diabetes mellitus rats involvement with entero-insular axis and GLP-1 via metabolomics study

The present study aimed to investigate the potential effects of white hyacinth bean polysaccharide (WHBP) against type 2 diabetic mellitus (T2DM) which was established by high-glucose/high-fat for 8 weeks, combined with a low-dose streptozotocin (STZ) injection. Our results showed that WHBP behaved the hypoglycemic effect by attenuating fasting blood glucose in vivo. WHBP-mediated anti-diabetic effects associated with the attenuation of insulin resistance and pancreatic impairment, as evidenced by the mitigation of pathological changes, inflammatory response and oxidative stress in the pancreas of T2DM rats. Meanwhile, gut protection was also shown during WHBP-mediated anti-diabetic effects, and glucagon-like peptide-1 (GLP-1), a mediator of the entero-insular axis, was observed to be elevated in both gut and pancreas of WHBP groups when compared to DM group, suggesting that hypoglycemic effects of WHBP were implicated in gut-pancreas interaction. Subsequently, untargeted metabolomics analysis performed by UPLC-QTOF/MS and showed that WHBP administration significantly adjusted the levels of 40 metabolites when compared to DM group. Further data concerning pathway analysis showed that WHBP administration significantly regulated the phenylalanine metabolism, tryptophan metabolism, arginine and proline, isoleucine metabolism, and glycerophospholipid metabolism in T2DM rats. Together, our results suggested that WHBP performed hypoglycemic effects and pancreatic protection linked to entero-insular axis involvement with GLP-1 and reversed metabolic disturbances in T2DM rats.

Pulmonary outcomes of incretin-based therapies in COPD patients receiving single-inhaler triple therapy

IntroductionPatients with chronic obstructive pulmonary disease (COPD) on triple therapy often face exacerbations and comorbidities. Emerging evidence suggests that glucagon-like peptide-1 (GLP-1) analogs may reduce the risk of exacerbation in patients with COPD and type 2 diabetes mellitus (T2DM). This study investigates the impact of GLP-1 analogs on pulmonary outcomes in patients with COPD on single-inhaler triple therapy (SITT) and T2DM.MethodsWe conducted a retrospective cohort study using the TriNetX database and analysed adult patients with COPD and T2DM who received SITT between April 2005 and July 2023. Patients were categorized into GLP-1 analog and dipeptidyl peptidase-4 inhibitors (DPP4i) cohorts. The primary efficacy outcome was COPD exacerbation and the secondary efficacy outcomes were pneumonia, acute respiratory distress syndrome, intubation, oxygen dependence, and all-cause mortality. The secondary outcomes were serious gastrointestinal adverse events.ResultsWe included 6898 patients, with 4184 receiving GLP-1 analogs and 2714 receiving DPP4i. After matching, 1751 GLP-1 analog users were matched with 1751 DPP4i users. GLP-1 analog users had an 18% lower risk of COPD exacerbation (hazard ratio [HR], 0.82 [95% CI: 0.71–0.94]), a 28% reduced risk of pneumonia (HR, 0.72 [95% CI: 0.61–0.85]), a 34% reduced risk of oxygen dependence (HR, 0.66 [95% CI: 0.47–0.91]), and a 40% decreased risk of all-cause mortality (HR, 0.60 [95% CI: 0.47–0.77]). No significant serious gastrointestinal adverse events were observed.ConclusionGLP-1 analogs may be associated with reduced COPD exacerbations, pulmonary comorbidities, and mortality in patients with COPD receiving SITT and T2DM, with no significant serious gastrointestinal safety concerns.

Impaired brain glucose metabolism in glucagon-like peptide-1 receptor knockout mice

BackgroundQuantitative mapping of the brain’s metabolism is a critical tool in studying and diagnosing many conditions, from obesity to neurodegenerative diseases. In particular, noninvasive approaches are urgently required. Recently, there have been promising drug development approaches for the treatment of disorders related to glucose metabolism in the brain and, therefore, against obesity-associated diseases. One of the most important drug targets to emerge has been the Glucagon-like peptide-1 (GLP-1) and its receptor (GLP-1R). GLP and GLP-1R play an important role in regulating blood sugar and maintaining energy homeostasis. However, the macroscopic effects on brain metabolism and function due to the presence of GLP-1R are unclear.MethodsTo explore the physiological role of GLP-1R in mouse brain glucose metabolism, and its relationship to brain function, we used three methods. We used deuterium magnetic resonance spectroscopy (DMRS) to provide quantitative information about metabolic flux, fluorodeoxyglucose positron emission tomography (FDG-PET) to measure brain glucose metabolism, and resting state-functional MRI (rs-fMRI) to measure brain functional connectivity. We used these methods in both mice with complete GLP-1R knockout (GLP-1R KO) and wild-type C57BL/6N (WT) mice.ResultsThe metabolic rate of GLP-1R KO mice was significantly slower than that of WT mice (p = 0.0345, WT mice 0.02335 ± 0.057 mM/min, GLP-1R KO mice 0.01998 ± 0.07 mM/min). Quantification of the mean [18F]FDG signal in the whole brain also showed significantly reduced glucose uptake in GLP-1R KO mice versus control mice (p = 0.0314). Observing rs-fMRI, the functional brain connectivity in GLP-1R KO mice was significantly lower than that in the WT group (p = 0.0032 for gFCD, p = 0.0002 for whole-brain correlation, p < 0.0001 for ALFF).ConclusionsGLP-1R KO mice exhibit impaired brain glucose metabolism to high doses of exogenous glucose, and they also have reduced functional connectivity. This suggests that the GLP-1R KO mouse model may serve as a model for correlated metabolic and functional connectivity loss.

Postprandial plasma aminoacidemia and indices of appetite regulation following pea-rice blend, pea isolate and whey protein ingestion in healthy young adults.

Plant-derived proteins are often deficient in essential amino acids and have lower rates of digestibility than animal-derived proteins. Blending different plant-derived proteins could compensate for these deficiencies and may augment postprandial aminoacidemia over single-source plant proteins. This study assessed plasma amino acids and appetite hormones, appetite sensations and ad libitum energy intake following ingestion of a pea-rice protein blend (BLEND), compared with pea-only (PEA) and whey (WHEY) protein. In a randomised, double-blind, crossover design, ten healthy adults (M n 4, F n 6; mean (sd) age 22 (sd 3) years; BMI 24 (sd 3) kg·m2) ingested 0·3 g·kg·body mass-1 of BLEND, PEA or WHEY. Arterialised venous blood samples and appetite ratings were obtained in the fasted state and over 240 min postprandially. Energy intake was measured via an ad libitum buffet-style test meal. Mean plasma essential amino acid incremental AUC was higher in WHEY, compared with PEA (P < 0·01; mean diff (95 % CI): 44218 (15806, 72631) μmol·240 min·l-1) and BLEND (P < 0·01; 14358 (16031, 101121) μmol·240 min·l-1), with no differences between PEA and BLEND (P = 0·67). Plasma ghrelin and glucagon-like peptide-1, appetite ratings and ad libitum energy intake responses did not differ between treatments (P > 0·05 for all). Ingestion of a pea-rice protein blend did not augment postprandial aminoacidemia above pea protein, perhaps attributable to marginal differences in essential amino acid composition. No between-treatment differences in appetite or energy intake responses were apparent, suggesting that the influence of protein ingestion on perceived appetite ratings and orexigenic hormonal responses may not be solely determined by postprandial plasma aminoacidemia.

Humulus lupulus L.: Evaluation of Phytochemical Profile and Activation of Bitter Taste Receptors to Regulate Appetite and Satiety in Intestinal Secretin Tumor Cell Line (STC-1 Cells).

Inflorescences of the female hop plant (Humulus lupulus L.) contain biologically active compounds, most of which have a bitter taste. Given the rising global obesity rates, there is much increasing interest in bitter taste receptors (TAS2Rs). Intestinal TAS2Rs can have beneficial effects on obesity when activated by bitter agonists. This study aims to investigate the mechanism of action of a hydroalcoholic hop extract in promoting hormone secretion that reduces the sense of hunger at the intestinal level through the interaction with TAS2Rs. The results demonstrate that the hop extract is a rich source of bitter compounds (mainly α-, β-acids) that stimulate the secretion of anorexigenic peptides (glucagon-like peptide 1 [GLP-1], cholecystokinin [CCK]) in a calcium-dependent manner while reducing levels of hunger-related hormones like ghrelin. This effect is mediated through interaction with TAS2Rs, particularly Tas2r138 and Tas2r120, and through the activation of downstream signaling cascades. Knockdown of these receptors using siRNA transfection and inhibition of Trpm5, Plcβ-2, and other calcium channels significantly reduces the hop-induced calcium response as well as GLP-1 and CCK secretion. This study provides a potential application of H. lupulus extract for the formulation of food supplements with satiating activity capable of preventing or combating obesity.

Weight Loss Therapies and Hypertension Benefits.

Obesity and hypertension have become an international health issue, with detrimental consequences on patients. Obesity and hypertension share common pathophysiological mechanisms, such as overactivity of the renin-angiotensin-aldosterone and the sympathetic nervous systems, insulin resistance, and disruption of the leptin pathway. Approved therapies for obesity and overweight include phentermine/topiramate, orlistat, naltrexone/bupropion, the glucagon-like peptide-1 receptor agonists liraglutide and semaglutide, tirzepatide, and bariatric surgery. This review gives the clinical data in a thorough manner and explains in detail how each of the previously mentioned therapies affects blood pressure levels.

Glucagon-like peptide-1 receptor agonists improve outcomes in individuals with type 2 diabetes with and without heart failure

BackgroundThe effectiveness of glucagon-like peptide-1 receptor agonists (GLP1Ras) for prevention of heart failure (HF) in patients with type 2 diabetes (T2DM) without HF and for risk of death in patients with T2DM with HF has not been fully elucidated in routine clinical practice. MethodsUsing the real-world global electronic medical record TriNetX database, individuals with T2DM and with or without HF who initiated either GLP1Ras or sitagliptin from 2017 to 2020 were retrospectively analyzed. In individuals with T2DM without HF, the primary outcome was a composite of all-cause mortality and a new diagnosis of HF within three years. In individuals with T2DM with HF, the primary outcome was all-cause mortality within three years. Propensity-score (PS) matching was used to adjust for over 100 baseline characteristics. ResultsA total of 65,598 individuals with T2DM without HF starting a GLP1Ras were PS matched with 65,598 starting sitagliptin. GLP1Ras were associated with a lower incidence of the composite endpoint (10.5 % versus 11.8 %, hazard ratio [HR] 0.82, [0.80–0.85], p < 0.001), mortality (HR 0.66 [0.63–0.69]) and new diagnosis of HF (HR 0.92 [0.88–0.96]). There were 6002 individuals in each group matched for T2DM and HF. Mortality was lower in the GLP1Ras group (17.6 % versus 22.8 %, HR 0.70 [0.65–0.76], p < 0.001). Results were consistent across subgroups. ConclusionsIn this global real-world data analysis, GLP1Ra use was associated with a lower risk of death and HF in individuals with T2DM without HF, and lower risk of death in those with HF.

A retrospective evaluation of glucagon-like peptide-1 receptor agonists in systemic lupus erythematosus patients.

Glucagon-like peptide-1 receptor agonists (GLP1-RA) are an emerging class of medications with demonstrated promise in improving cardiometabolic outcomes. Whether these drugs may be useful in mitigating the cardiac risk associated with SLE remains unknown, and a recent case of drug induced lupus secondary to GLP1-RA use calls the safety of GLP1-RAs in SLE patients into question. Accordingly, this retrospective analysis was initiated to evaluate outcomes of GLP1-RAs in SLE. All patients in the NYU Lupus Cohort who had used a GLP1-RA were eligible for inclusion. Patient characteristics were assessed at baseline (most recent rheumatology visit prior to starting GLP1-RA), 1-4 months, and 6-10 months after GLP1-RA initiation. Of the 1211 patients in the cohort, only 24 had received a GLP1-RA. Six were excluded due to insufficient documentation regarding duration of medication use. Of the remaining 18 (median age 50), 17 (94%) were female and 9 (50%) were white. There was one mild-to-moderate flare at 6-10 months, but no patients accumulated new SLE criteria during the follow up period. Compared with baseline, median BMI was reduced by 3% at 1-4 months (p= 0.002) and 13% at 6-10 months (p= 0.001). Nine (50%) patients were initially denied insurance coverage for a GLP1-RA. While limited by a small sample size, this descriptive study showed that GLP1-RAs did not trigger flares above expected background rates and were associated with significantly decreased BMI. Future studies exploring the potential benefits of GLP1-RAs in patients with SLE are warranted.

Glucagon-like peptide-1 receptor agonists significantly affect the quality of bowel preparation for colonoscopy.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) affect gastrointestinal motility, slowing gastric emptying and colonic transit. GLP-1RAs have an impact on gastric residue before endoscopy, but only limited data are available regarding its effect on the adequacy of colonic preparation. We investigated the association between GLP-1RA use and inadequate bowel preparation (IBP) for colonoscopy. We performed a multicenter retrospective study with GLP-1RA cases matched with controls (using propensity scores for age, sex, diabetes mellitus [DM], obesity, and co-morbidities). Data on demographics, medication use, procedural indications, and colonoscopy findings were collected. IBP ("poor preparation" on Aronchik scale or Boston Bowel preparation scale <5) was the primary outcome. 4876 patients treated with GLP-1RAs were included in the analysis and compared with 4876 controls selected from 333 648 patients without GLP-1RA use. Among the GLP-1RA patients, 10% (n = 487) had IBP compared with 197 (4%) of the control group (P<0.001). Subgroup analysis showed a higher rate of IBP among diabetic patients treated with GLP-1RA (284/2364 [12%]) than among diabetic patients without GLP-1RA treatment (118/2364 [5%]; P<0.001). Additionally, 203/2512 nondiabetic patients treated with GLP-1RAs had IBP (8%) compared with 79 of the nondiabetic non-GLP-1RA group (3%; P<0.001). On multivariate analysis, diabetes and GLP-1RA use were both found to be independent risk factors for IBP (odds ratio [OR] 1.4 and OR 2.7, respectively; both P<0.001). Our findings highlight the necessity for special attention and tailored recommendations for both diabetic and nondiabetic patients treated with GLP-1RAs in terms of colonic preparation prior to colonoscopy.

The Cardiometabolic Risk in Women with Polycystic Ovarian Syndrome (PCOS): From Pathophysiology to Diagnosis and Treatment.

Polycystic Ovarian Syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age, with significant variations in presentation characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. Beyond reproductive health, it may also pose crucial long-term cardiometabolic risks, especially for women with specific types of PCOS, contributing to early subclinical cardiovascular atherosclerotic alterations such as endothelial dysfunction, increased arterial stiffness, and coronary artery calcium levels, respectively. Moreover, the precise relationship between clinical cardiovascular disease (CVD) and PCOS remains debated, with studies demonstrating an elevated risk while others report no significant association. This review investigates the pathophysiology of PCOS, focusing on insulin resistance and its link to subclinical and clinical cardiovascular disease. Diagnostic challenges and novel management strategies, including lifestyle interventions, medications like metformin and glucagon-like peptide-1 receptor agonists (GLP-1RAs), hormonal contraceptives, and bariatric surgery, are further discussed. Recognizing the cardiometabolic risks associated with PCOS, a comprehensive approach and early intervention should address both the reproductive and cardiometabolic dimensions of the syndrome.

In adults with type 2 diabetes, what are the comparative benefits and risks of sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors versus glucagon-like peptide-1 (GLP-1) receptor agonists?

In adults with type 2 diabetes, what are the comparative benefits and risks of sodium-glucose cotransporter protein-2 (SGLT-2) inhibitors versus glucagon-like peptide-1 (GLP-1) receptor agonists?

Kidney Outcomes with GLP-1RAs, SGLT2 Inhibitors, DPP-4 Inhibitors, and Sulfonylureas in Type 2 Diabetes and Moderate Cardiovascular Risk

Background: Chronic kidney disease (CKD) is a serious diabetes-related complication. While guidelines recommend use of sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists to mitigate cardiorenal risk in high-risk patients, the benefit of early initiation of these agents relative to other commonly prescribed glucose-lowering agents in patients at lower baseline cardiovascular disease (CVD) risk remains less clear. Methods: This retrospective observational study emulated an idealized target trial using claims data from OptumLabs® Data Warehouse to test the comparative association of treatment with a dipeptidyl peptidase-4 (DPP-4) inhibitor, SGLT2 inhibitor, GLP-1 receptor agonist, or sulfonylurea on a primary kidney composite outcome of incident CKD stages 3-5, kidney failure, or need for kidney replacement therapy (KRT) in patients with type 2 diabetes (T2D) and moderate CVD risk. A secondary composite outcome included all components of the primary composite outcome plus death. Results: A total of 364,714 adults ≥21 years of age initiating treatment with a DPP-4 inhibitor (N=78,843), GLP-1 receptor agonist (N=42,049), SGLT2 inhibitor (N=45,466), or sulfonylurea (N=198,356) were identified. Relative to DPP-4 inhibitor, SGLT2 inhibitor (HR: 0.71; 95% CI: 0.67-0.74; P˂0.001) and GLP-1 receptor agonist (HR: 0.87; 95% CI: 0.83-0.92; P˂0.001) treatment was superior for the primary composite outcome. Similarly, SGLT2 inhibitor (HR: 0.69; CI: 0.66-0.73) and GLP-1 receptor agonist (HR: 0.86; CI: 0.82-0.91) treatment was associated with risk reductions for the primary outcome relative to sulfonylurea treatment. When comparing SGLT2 inhibitor to GLP-1 receptor agonist therapy, SGLT2 inhibitors were superior for the primary composite outcome (HR: 0.81; 95% CI: 0.75-0.76; P˂0.001). Similar findings were observed for the secondary composite outcome across all comparisons. Conclusions: SGLT2 inhibitors and GLP-1 receptor agonists were superior to DPP-4 inhibitors and sulfonylurea for preventing kidney complications in a T2D population with moderate baseline CVD risk.

How Would You Manage This Patient With Obesity? Grand Rounds Discussion From Beth Israel Deaconess Medical Center.

In 2022, 1 in 8 people in the world were living with obesity, and lifestyle interventions that include diet, exercise, and behavioral modification have been the foundation for management of obesity. Recently, pharmacologic therapies have been developed for management of obesity, the newest of these being glucagon-like peptide 1 receptor agonists. With the development of new pharmacologic options, the American Gastroenterological Association developed a guideline in 2022 to provide evidence-based recommendations for the pharmacologic management of obesity in adults and recommended, for adults with obesity or overweight with weight-related complications who have had an inadequate response to lifestyle interventions, adding pharmacologic agents to lifestyle interventions over continuing lifestyle interventions alone. In this article, 2 experts review the available evidence to answer the following questions: How effective are lifestyle interventions for the treatment of obesity? How effective are pharmacologic interventions for the treatment of obesity? Given these options, how do you engage in a shared decision-making discussion to develop a mutually agreed-on treatment plan?

Retrospective Analysis Comparing the Efficacy of GLP-1 Receptor Agonists Dulaglutide and Semaglutide

Background: Glucagon-like peptide-1 receptor agonists have gained popularity in recent years because of their well-established benefits of increased glycemic control, weight loss, cardiovascular protection, and renal protection, with minimal adverse effects, and low risk for hypoglycemia in patients with type 2 diabetes. This study explored the effectiveness of the GLP-1 receptor agonist semaglutide and dulaglutide on body weight and hemoglobin A1c in patients with type 2 diabetes. Methods: In this retrospective cohort study, 244 patients diagnosed with type 2 diabetes and prescribed semaglutide or dulaglutide were identified through Lourdes Hospital electronic medical records. Over a 12-month period, in set intervals every 3 months, patients were assessed for changes in their hemoglobin A1c and body weight measured as a reduction in their body mass index (BMI). These primary outcomes were compared using linear mixed models from the lme4 package in R (v. 4.2.2). Results: Semaglutide and dulaglutide showed comparable effectiveness in reducing hemoglobin A1c compared with baseline. Both medications also led to a reduction in BMI. However, semaglutide showed statistically significant improvements in weight loss compared with dulaglutide at 3-6 months ( P = 0.01), 6-9 months ( P = 0.01), and 9-12 months ( P = 0.01). Conclusions: These findings suggest that in type 2 diabetes, semaglutide and dulaglutide show comparable effectiveness in reducing hemoglobin A1c. However, semaglutide was shown to be more effective in promoting weight loss. While these findings may be beneficial when treating patients with type 2 diabetes and obesity, treatment should be individualized to the patient, considering all factors before treatment choice.