Glucagon-like peptide-1 analogs activate AMP kinase leading to reversal of the Warburg metabolic switch in breast cancer cells.

Breast cancer (BC) is associated with type 2 diabetes mellitus (T2DM) and obesity. Glucagon-like peptide (GLP)-1 regulates post-prandial insulin secretion, satiety, and gastric emptying. Several GLP-1 analogs have been FDA-approved for the treatment of T2DM and obesity. Moreover, GLP-1 regulates various metabolic activities across different tissues by activating metabolic signaling pathways like adenosine monophosphate (AMP) activated protein kinase (AMPK), and AKT. Rewiring metabolic pathways is a recognized hallmark of cancer, regulated by several cancer-related pathways, including AKT and AMPK. As GLP-1 regulates AKT and AMPK, we hypothesized that it alters BC cells' metabolism, thus inhibiting proliferation. The effect of the GLP-1 analogs exendin-4 (Ex4) and liraglutide on viability, AMPK signaling and metabolism of BC cell lines were assessed. Viability of BC cells was evaluated using colony formation and MTT/XTT assays. Activation of AMPK and related signaling effects were evaluated using western blot. Metabolism effects were measured for glucose, lactate and ATP. Exendin-4 and liraglutide activated AMPK in a cAMP-dependent manner. Blocking Ex4-induced activation of AMPK by inhibition of AMPK restored cell viability. Interestingly, Ex4 and liraglutide reduced the levels of glycolytic metabolites and decreased ATP production, suggesting that GLP-1 analogs impair glycolysis. Notably, inhibiting AMPK reversed the decline in ATP levels, highlighting the role of AMPK in this process. These results establish a novel signaling pathway for GLP-1 in BC cells through cAMP and AMPK modulation affecting proliferation and metabolism. This study suggests that GLP-1 analogs should be considered for diabetic patients with BC.

Emerging drugs for the treatment of short bowel syndrome.

INTRODUCTION: SBS is a rare and disabling condition. The standard management is based on diet optimization with parenteral supplementation. In addition, glucagon-like peptide-2 (GLP-2)analogs, have shown promising results as disease-modifying therapies for SBS. AREAS COVERED: Short bowel syndrome (SBS) is defined as a reduction in functional intestinal length to less than 200 cm, leading to intestinal failure (IF) leading to malnutrition and parenteral support dependency. This review discusses the current management of SBS-CIFpatients, the place of GLP-2 analog treatment in terms of efficacy, safety and availability, and the new perspectives opened by the use of enterohormones. EXPERT OPINION: Clinical trials and real-world experience demonstrated that Teduglutide   reduces dependence on parenteral support and has a place in the management of patients with SBS-CIF.  The use of Teduglutide should be discussed in patients stabilized after resection and its introduction requires the advice of an expert center capable of assessing the benefit-risk ratio. The complex, individualized management of SBS-C IF requires theexpertise of a specialized IF center which a multidisciplinary approach. The arrival of new treatments will call for new therapeutic strategies, and the question of how to introduce and monitor them will represent a new therapeutic challenge.

Effects of semaglutide-loaded lipid nanocapsules on metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent chronic liver disease that can progress to end-stage conditions with life-threatening complications, but no pharmacologic therapy has been approved. Drug delivery systems such as lipid nanocapsules (LNC) are very versatile platforms that are easy to produce and can induce the secretion of the native glucagon-like peptide 1 (GLP-1) when orally administered. GLP-1 analogs are currently being studied in clinical trials in the context of MASLD. Our nanosystem provides with increased levels of the native GLP-1 and increased plasmatic absorption of the encapsulated GLP-1 analog (semaglutide). Our goal was to use our strategy to demonstrate a better outcome and a greater impact on the metabolic syndrome associated with MASLD and on liver disease progression with our strategy compared with the oral marketed version of semaglutide, Rybelsus®. Therefore, we studied the effect of our nanocarriers on a dietary mouse model of MASLD, the Western diet model, during a daily chronic treatment of 4 weeks. Overall, the results showed a positive impact of semaglutide-loaded lipid nanocapsules towards the normalization of glucose homeostasis and insulin resistance. In the liver, there were no significant changes in lipid accumulation, but an improvement in markers related to inflammation was observed. Overall, our strategy had a positive trend on the metabolic syndrome and at reducing inflammation, mitigating the progression of the disease. Oral administration of the nanosystem was more efficient at preventing the progression of the disease to more severe states when compared to the administration of Rybelsus®, as a suspension.

Contemporary Management of Obesity: A Comparison of Bariatric Metabolic Surgery and Novel Incretin Mimetic Drugs.

The global prevalence of obesity has risen sharply during the past half-century, reaching pandemic proportions and creating a public health crisis. Obesity is a recognized risk factor for the development of diabetes, atherosclerosis, hypertension, hepatic steatosis, and many other cardiometabolic disorders with significant resultant morbidity and mortality. Though treatment of obesity can prevent or slow the progression of the aforementioned illnesses, efforts to help patients achieve reliable and sustainable weight loss have had limited success. Improving nutrition and increasing physical activity results in a host of health benefits; however, the weight loss achieved with lifestyle interventions alone is modest and difficult to sustain. Early attempts at medical and surgical treatment of obesity were plagued with adverse effects and complications. Moreover, these approaches failed to demonstrate long-term health benefits, even when weight loss was achieved. Recently, novel incretin-based therapies targeting glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors have gained popularity because of their effectiveness in achieving substantial weight loss in patients both with and without diabetes. Following many successful clinical trials, there are now multiple GLP-1 receptor agonists and one dual GLP-1-GIP receptor agonist approved by the Food and Drug Administration for chronic weight management. Advancements in laparoscopic surgical technique and refinements in procedure selection have similarly improved the safety and efficacy of bariatric metabolic surgery for patients with obesity. In this review, we discuss the advantages and disadvantages of contemporary pharmacologic and surgical weight management strategies. We review the data regarding expected weight loss, glycemic control, cardiometabolic benefits, and potential adverse effects of various treatment approaches. As obesity rates continue to rise worldwide, it is imperative that clinicians keep these considerations in mind in order to better care for patients.

Pharmacotherapy for obesity: moving towards efficacy improvement.

Obesity is a chronic, recurring, progressive disease and a major public health problem associated with several other diseases that lead to disability, morbidity, and mortality. The prevalence of obesity has increased at pandemic levels, along with increasing weight-related comorbidities and deaths worldwide. Lifestyle interventions alone provide clinically significant long-term weight loss in only a small proportion of individuals, and bariatric surgery is not suitable or desirable for all patients. Historically, anti-obesity medications achieved a mean efficacy with weight loss between 5 and 10%, which significantly impacted several comorbidities and risk factors, but the average efficacy of these medications remained lower than that expected by both patients and health care professionals and eventually curbed long-term use. Moreover, there is no direct evidence on the impact of anti-obesity medications on cardiovascular outcomes. Semaglutide is a newer anti-obesity medication that changes the overall landscape, as phase 3 studies show a mean weight loss near the 15% threshold and significant proportions of patients with a weight loss of greater than 20%. In this review, we focus on the currently available anti-obesity medications, discuss the results of semaglutide, and present perspectives on the future of obesity treatment after semaglutide.

GLP-1 Analogs, SGLT-2, and DPP-4 Inhibitors: A Triad of Hope for Alzheimer's Disease Therapy.

Alzheimer's is a prevalent, progressive neurodegenerative disease marked by cognitive decline and memory loss. The disease's development involves various pathomechanisms, including amyloid-beta accumulation, neurofibrillary tangles, oxidative stress, inflammation, and mitochondrial dysfunction. Recent research suggests that antidiabetic drugs may enhance neuronal survival and cognitive function in diabetes. Given the well-documented correlation between diabetes and Alzheimer's disease and the potential shared mechanisms, this review aimed to comprehensively assess the potential of new-generation anti-diabetic drugs, such as GLP-1 analogs, SGLT-2 inhibitors, and DPP-4 inhibitors, as promising therapeutic approaches for Alzheimer's disease. This review aims to comprehensively assess the potential therapeutic applications of novel-generation antidiabetic drugs, including GLP-1 analogs, SGLT-2 inhibitors, and DPP-4 inhibitors, in the context of Alzheimer's disease. In our considered opinion, antidiabetic drugs offer a promising avenue for groundbreaking developments and have the potential to revolutionize the landscape of Alzheimer's disease treatment.

Automated versus manual prior authorization for diabetes mellitus drugs: A retrospective study from Israel.

Introduction: Drug prior authorization (PA) imposes a bureaucratic and economic burden on healthcare service providers and payers. A novel automated PA system may improve these drawbacks. Methods: An historical cohort study from a large health maintenance organization in Israel, comparing manual versus automated PA mechanisms for diabetes mellitus (DM) drugs: sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 analogs (GLP1-A). We compared patients with DM, whose first drug applications were approved using the automated system, with similar patients whose first drug applications were approved by manual PA. The primary endpoint was the time elapsed from application approval to prescription filling (accessibility time). Secondary endpoints included the prescription filling rate at 7 and 30 days. Results: In total, 1371 automated approved prescriptions and 1240 manually approved prescriptions were included in the analysis. Median accessibility time was one day (interquartile range (IQR) 0-5) with automated PA for both GLP1-A and SGLT2i, compared with four days (IQR 1-9) and three days (IQR 1-8), respectively, with the manual PA (p < 0.001). Eighty-four percent of GLP1-A automated PA approvals were filled within seven days compared with 70% with manual PA (p < 0.001). Similar results were seen with SGLT2i (80% vs. 72%, p < 0.008). No differences were observed at 30 days post-approval. Using logistic regression, odds for GLP1-A and SGLT2i prescription filling within seven days were 2.36 and 1.53 folds higher (respectively) with automated PA (p < 0.01). Conclusions: Automated PA system improved access time to SGLT2i/GLP1-A seven days post-approval compared to manual PA.

A Visual Diagnosis: Lipodystrophy.

Lipodystrophy syndromes are rare metabolic disorders characterized by local or generalized loss of adipose tissue, resulting in insulin resistance, dyslipidemia, and cosmetic disfiguration. The lipodystrophic phenotype is highly variable, with partial lipodystrophy often missed or misdiagnosed as other diseases from a lack of a proper physical examination and low physician awareness. Correct diagnosis is important for optimal treatment and follow-up strategies in these patients. The use of GLP-1 analogs has not been systematically evaluated in lipodystrophy and could be a potential precision medicine therapy. We aim to make the reader, particularly generalists or endocrinologists outside of tertiary referral centers, aware of the presentation and clinical features of partial lipodystrophy, emphasize the role of a full physical examination in diagnosis, and discuss therapeutic options, including GLP-1-based glycemic management illustrated by our clinical case.

Effects of Hypolipidemic Drugs on Psoriasis.

Psoriasis is a chronic, systematic, inflammatory disease in which multiple metabolic and immunologic disturbances lead to lipid abnormalities, impaired glucose tolerance, metabolic syndrome, diabetes mellitus, atherosclerosis, hypertension, ischemic heart disease, and numerous metabolic disorders. In clinical practice, the most commonly used drugs in the treatment of lipid abnormalities are statins and fibrates. Statins are characterized by pleiotropic effects such as antioxidant, anti-inflammatory, anticoagulant, and antiproliferative. They work by reducing the concentrations of low-density lipoprotein (LDL), total cholesterol, and triglycerides and stabilizing atherosclerotic plaque. Fibrates are medications, which help to lower triglycerides, LDL, very low-density lipoprotein (VLDL) levels and increase lower high-density lipoprotein (HDL). In recent years, many new drugs were found to normalize the lipid profile in patients with psoriasis: glitazones (pioglitazone, troglitazone), and glucagon-like peptide-1 (GLP-1) receptor agonists. Pioglitazone improves the lipid profile, including the decrease of triglycerides, fatty acids, and LDL, as well as the increase of HDL. Glucagon-like peptide 1 (GLP-1) analogs decrease modestly low-density lipoprotein cholesterol (LDL-C), total cholesterol, and triglycerides. The purpose of this study is to assess the current state of knowledge on the effect of different hypolipidemic treatments on the course of psoriasis. The study includes literature from medical databases PubMed and Google Scholar. We were browsing PubMed and Google Scholar until the beginning of December. The systematic review includes 41 eligible original articles.

Novel LC-MS/MS analysis of the GLP-1 analog semaglutide with its application to pharmacokinetics and brain distribution studies in rats.

Semaglutide, one of the most potent glucagon-like peptide (GLP)-1 analogs, has widely been used to treat type II diabetes mellitus and obesity. Recent studies have shown that semaglutide also works on the brain, suggesting its potential utility for various diseases, including Parkinson's disease and Alzheimer's disease. This study aimed to develop a novel liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis of semaglutide in both plasma and brain to characterize the pharmacokinetics and brain distribution in rats. Semaglutide was extracted by simple protein precipitation with methanol from plasma and by solid phase extraction from brain tissue. Liraglutide was used as an internal standard. Gradient elution profiles with mobile phases comprising 0.1 % formic acid in water and acetonitrile were used for chromatographic separation. The lower limit of quantification (LLOQ) of the LC-MS/MS assay was 0.5 ng/mL for both rat plasma and brain. Intra- and inter-day accuracy ranged 89.20-109.50 % in the plasma and 92.00-105.00 % in the brain. Precision was within 8.92 % in the plasma and 7.94 % in the brain. Sprague-Dawley rats were given semaglutide by intravenous (IV, 0.02 mg/kg) and subcutaneous (SC, 0.1 and 0.2 mg/kg) injection. Plasma concentrations of semaglutide showed a multi-exponential decline with an average half-life of 7.22-9.26 hr in rats. The subcutaneous bioavailability of semaglutide was 76.65-82.85 %. The brain tissue to plasma partition coefficient (Kp) value of semaglutide was estimated as <0.01. Among the different regions of the brain, semaglutide concentrations were significantly higher in the hypothalamus. The analytical method and pharmacokinetic information may be helpful toward a better understanding of the effect of semaglutide in the brain and further development of GLP-1 analogs for various brain diseases.

Metabolically healthy obesity: Misleading phrase or healthy phenotype?

Obesity is a heterogenous condition with multiple different phenotypes. Among these a particular subtype exists named as metabolically healthy obesity (MHO). MHO has multiple definitions and its prevalence varies according to study. The potential mechanisms underlying the pathophysiology of MHO include the different types of adipose tissue and their distribution, the role of hormones, inflammation, diet, the intestinal microbiota and genetic factors. In contrast to the negative metabolic profile associated with metabolically unhealthy obesity (MUO), MHO has relatively favorable metabolic characteristics. Nevertheless, MHO is still associated with many important chronic diseases including cardiovascular disease, hypertension, type 2 diabetes, chronic kidney disease as well as certain types of cancer and has the risk of progression into the unhealthy phenotype. Therefore, it should not be considered as a benign condition. The major therapeutic alternatives include dietary modifications, exercise, bariatric surgery and certain medications including glucagon-like peptide-1 (GLP-1) analogs, sodium-glucose cotransporter-2 (SGLT-2) inhibitors and tirzepatide. In this review, we discuss the significance of MHO while comparing this phenotype with MUO.

The Future of Diabetes Therapies: New Insulins and Insulin Delivery Systems, Glucagon-Like Peptide 1 Analogs, Sodium-Glucose Cotransporter Type 2 Inhibitors, and Beta Cell Replacement Therapy.

As the prevalence of diabetes mellitus increases, so too does the number of available treatment modalities. Many diabetic therapies available in human medicine or on the horizon could hold promise in the management of small animal diabetes. However, it is important to consider how species differences in pathophysiology, management practices and goals, and lifestyle may affect the translation of such treatment modalities for veterinary use. This review article aimed to familiarize veterinarians with the more promising novel diabetic therapies and explore their possible applications in the treatment of canine and feline diabetes mellitus.

The Impact of Various Methods of Obesity Treatment on the Quality of Life and Mental Health-A Narrative Review.

Obesity, defined as body mass index (BMI) ≥ 30 kg/m2, is one of the most important public health problems. Over one billion people are obese, including 650 million adults, which is 13% of the worldwide population, according to the World Health Organization (WHO). Similar to obesity, mental disorders such as depression and anxiety are huge social problems with serious health implications. There are numerous studies proving a strong link between the prevalence of obesity and depressive disorders, and being overweight is also associated with decreased health-related quality of life (HRQoL). Due to the broad negative impact of obesity on a patient's health, proper treatment is crucial. Currently, the literature describes many methods of treatment such as dietary treatment, pharmacotherapy using glucagon-like peptide-1 (GLP-1) analogs, orlistat, naltrexone/bupropion (NB), or finally bariatric surgery. The most commonly used methods of obesity treatment significantly improve the patient's quality of life and reduce the symptoms of depression and anxiety. The aim of our study was to summarize the knowledge about the impact of known and commonly used methods of obesity treatment (e.g., dietary treatment, bariatric surgery, and pharmacological treatment) on mental health and quality of life. For this purpose, we will try to review the current scientific data, originating from international reports.

Role of Liraglutide Use in Patients With Heart Failure.

Heart failure is a clinical condition in which the heart is unable to maintain adequate cardiac output. Liraglutide is a glucagon-like peptide 1 (GLP-1) analogue that is used for the treatment of type 2 diabetes mellitus, but recent evidence suggests that it might have a beneficial role in treating heart failure. We conducted a review of existing literature and found five relevant studies. Data from these studies were extracted and then extrapolated into results following analysis. Four of the five studies found an increase in heart rate in heart failure patients. All five studies reported an increased rate of hospitalization. The five studies also showed an increased risk of adverse effects such as arrhythmia, ventricular tachycardia, atrial fibrillation, and worsening of heart failure. Given the scarcity of evidence in the available literature on liraglutide in heart failure, more research on this population is required.

Liraglutide Effect on Weight, Glycated Hemoglobin, and Blood Pressure: A Single-Center Experience in the Eastern Province of Saudi Arabia.

Background Liraglutide has pleiotropic effects beneficial to patients with cardiovascular and renal risks. These effects have been linked to weight and blood pressure reduction in type 2 diabetes (T2D) patients. However, whether this reduction is similar in all patients regardless of their ethnicity, baseline demographic, or clinical characteristics is unknown. This study aimed to identify the efficacy of liraglutide on weight, glycated hemoglobin (HbA1c), and blood pressure in Saudi patients with T2D who attended King Fahad Hospital of the University and received liraglutide as add-on therapy to other antihyperglycemic agents. The study also aimed to describe the pattern of change in these clinical parameters before and after the treatment and assess whether sex differences affect liraglutide's efficacy. Methods We conducted a retrospective longitudinal study reviewing medical records of 220 Saudi patients with T2D treated at King Fahad Hospital of the University (KFHU), in Al-Khobar city in the Eastern Province of Saudi Arabia, from December 2016 to November 2021. Patient cases were included if the patient was Saudi, aged 18 or older, and received liraglutide in a dose of at least 0.6 mg/day for at least three months in combination with other antihyperglycemic agents/diabetes medications. We recorded the effect on patient HbA1c, systolic blood pressure (SBP) and diastolic blood pressure (DBP), body mass index (BMI), and body weight at baseline, during, and after treatment. We used the paired t-test and repeated measure analysis of variance to compare the mean study parameters before and after treatment. Furthermore, an independent t-test was used to compare the mean study parameters among men and women. Results Treatment with liraglutide from 0.6 mg/day to 3 mg/day for three to 18 months had optimal results across the outcomes measured in our cohort study. There was a significant reduction in weight from baseline to 18 months from a mean weight of 97.9±20 kg to 96.51±18.45 kg with (p<0.001). Mean HbA1c at baseline was 9.34%±1.95%, dropped to 7.67%±1.11% (p<0.001) at 18 months. Moreover, mean SBP also significantly decreased from 126.61±10.4 mmHg to 122.48±7.29 mmHg by the last follow-up (p<0.001). Mean DBP was 76.54±8.37 mmHg at baseline and decreased to 74.29±6.22 mmHg at last follow-up (p<0.001). Men treated with liraglutide had greater reductions in weight than women throughout the study (p<0.05), and while men had greater reductions in SBP and DBP than women early in treatment (p<0.05), by the end of treatment, there were no significant differences in blood pressure between men and women. Likewise, we saw no significant difference between HbA1c reductions in men and women treated with liraglutide. Conclusion Liraglutide effectively reduces HbA1c, weight, BMI, SBP, and DBP in T2D patients. These study results reflect real-world liraglutide clinical practices from KFHU and can be beneficial for physicians when considering using liraglutide as add-on therapy in this population.

Efficacy of Glucagon-Like Peptide-1 Analogs in Nonalcoholic Fatty Liver Disease: A Systematic Review.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. It is believed to be the hepatic manifestation of the metabolic syndrome. Many treatment approaches have been suggested so far, and several types of studies have been done to find treatment for NAFLD, the most promising of which are those with lifestyle interventions. OBJECTIVE: The aim of this systematic review was to evaluate the efficacy and safety of glucagon-like peptide-1 (GLP-1) analogs on the management of NAFLD. METHODS: The PubMed, MEDLINE, and Cochrane Central Library were searched to identify randomized controlled trials, single arm trials, and cohorts that compared GLP-1 analogs with a control treatment or baseline values with respect to efficacy and safety in patients living with NAFLD. The key outcomes were a change in serum transaminase, resolution of disease status measured by imaging or histological techniques, improvement in insulin resistance, and reduction in body weight. RESULTS: Initial searching retrieved 201 peer-reviewed articles and abstracts. Ten studies met all inclusion criteria. The review included a total of 590 participants with NAFLD. Following administration of GLP-1 analogs, a decrease in serum transaminases, improvement in liver histology and insulin resistance, and a reduction in body weight were observed. Compared with baseline, body weight, alanine aminotransferase, aspartate aminotransferase, and gamma glutamyltransferase were decreased by 5.5%, 59.5%, 52.8%, and 44.8%, respectively, due to GLP-1. Likewise, a reduction of proinflammatory cytokines and fibrosis markers and an enhancement of protective adipokines were observed in some of the studies. CONCLUSION: The decrease in a key biochemical marker of liver injury following treatment with GLP-1 analogs, as well as improvements in imaging and histology, suggests that these agents may be effective alternatives for managing NAFLD. REGISTRATION: CRD42018087262.

GLP-1 receptor agonists in diabetes for stroke prevention: a systematic review and meta-analysis.

BACKGROUND: Randomized controlled clinical trials (RCT) have demonstrated varied efficacy of glucagon-like peptide-1 receptor (GLP-1R) agonists for cardiovascular outcomes. We sought to evaluate the efficacy and safety of GLP-1R agonists among patients with Type 2 diabetes mellitus (DM) for stroke prevention. METHODS: We conducted a systematic review and meta-analysis of RCTs reporting the following outcomes among patients with Type 2 DM treated with GLP-1R agonists (vs. placebo): nonfatal or fatal strokes, all-cause or cardiovascular mortality, myocardial infarction (MI) and major adverse cardiovascular events (MACE). The protocol of our systematic review and meta-analysis was registered to the PROSPERO database. We pooled odds ratios (OR) using random-effect models, and assessed the heterogeneity using Cochran Q and I2 statistics. RESULTS: We identified 8 RCTs, comprising 56,251 patients. In comparison to placebo, GLP-1R agonists reduced nonfatal strokes (OR 0.84; 95% CI 0.76-0.94, p = 0.002; I2 = 0%) and all strokes (OR 0.84; 95% CI 0.75-0.93, p = 0.001; I2 = 0%) by 16%. Overall, GLP-1R agonists reduced MACE by 13% (OR 0.87; 95% CI 0.81-0.94, p = 0.0003; I2 = 42%), cardiovascular mortality by 12% (OR 0.88; 95% CI 0.81-0.95; p = 0.002; I2 = 0%) and all-cause mortality by 12% (OR 0.88; 95% CI 0.82-0.95, p = 0.0007; I2 = 15%). Additional analyses demonstrated that GLP-1R agonists reduced the risk of incident MACE (OR 0.86; 95% CI 0.80-0.92; p < 0.0001; I2 = 0%) among patients with prior history of MI or nonfatal strokes. CONCLUSIONS: Among patients with type 2 DM, GLP-1R agonists are beneficial for primary stroke, MACE, and cardiovascular mortality prevention. Further RCTs are needed to evaluate their role for secondary stroke prevention.

Retinal neuroprotective effect of GLP-1 analogs liraglutide in early diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study glucagon-like peptide-1(GLP-1)analogues(liraglutide)in patients with mild to moderate nonproliferative diabetic retinopathy(NPDR)and the clinical efficacy of retinal neuroprotection.<p>METHODS: Sixty patients with type 2 diabetes mellitus with mild or moderate NPDR were treated in our department of endocrinology. They were randomly divided into two groups. Patients in the experimental group used metformin, insulin combined with liraglutide to regulate blood glucose, while the control group used metformin, insulin for hypoglycemia. Comparing the two groups of patients before and after the treatment, including HbA1c and pattern visual evoked potential(P-VEP)P100 amplitude and P100 latency, full field electroretinogram(F-ERG)oscillatory potentials(Ops)total amplitude, and light and dark adaptation 3.0 the amplitude of the a-, b-wave varies.<p>RESULTS: After 6mo treatment, the total amplitude of Ops in the experimental and control groups increased compared with that before treatment. The difference was statistically significant(all <i>P</i><0.01). And the total amplitude of Ops in the experimental group was higher than that of the control group, the difference was statistically significant(<i>P</i>=0.049). Meanwhile the b-wave amplitudes of the light and dark adaptation 3.0 in the experimental group were higher than those in the control group(<i>P</i>=0.001, <i>P</i>=0.014); however, there was no statistical significance in a-wave amplitude between the light and dark adaptation 3.0 in both groups after treatment(<i>P</i>=0.505, 0.441, 0.193, respectively). the b-wave amplitudes of the experimental group with dark and light adaptation 3.0 increased compared with that before treatment, and the difference was statistically significant(<i>P</i><0.01, <i>P</i>=0.019). The a-wave amplitude of light and dark adaptation in the experimental group increased compared with that before treatment, but the difference was not statistically significant(<i>P</i>=0.130, 0.147). <p>CONCLUSION: GLP-1 analogues can improve the function of retinal neurons in patients with mild to moderate NPDR to a certain extent, and have a positive effect on the prognosis of DR.