Glucagon-like peptide-1 analog, liraglutide, regulates Sertoli cell energy metabolism.

Liraglutide, an analog of the incretin hormone glucagon-like peptide 1 (GLP-1), is widely used for obesity and type 2 diabetes treatment. However, there is scarce information about its effects on testicular function. Within the testis, Sertoli cells (SCs) provide nutritional support for germ cells; they metabolize glucose to lactate, which is delivered to germ cells to be used as a preferred energy substrate. Besides, SCs use fatty acids (FAs) as an energy source and store them as triacylglycerols (TAGs) within lipid droplets (LDs), which serve as an important energy reserve. In the present study, 20-day-old rat SC cultures were used to assess whether liraglutide affects their metabolic functions related to nutritional support and lipid storage. The results show that liraglutide does not modify glucose consumption or lactate production. However, it increases TAG levels and LD content. These effects are accompanied by an increase in the mRNA levels of the fatty acid transporter FAT/CD36, glycerol-3-phosphate-acyltransferase 3, and perilipins 1 and 4. The participation of the cAMP/PKA signaling pathway was explored. We observed that H89 (a PKA inhibitor) decreases the LD upregulation elicited by liraglutide, and that dibutyryl cAMP increases LD content and the expression of related genes. In summary, liraglutide promotes lipid storage in SCs through the regulation of key regulatory genes involved in FA transport, TAG synthesis, and LD formation. Considering the importance of lipid storage in SC energetic homeostasis maintenance, we postulate that liraglutide might improve the overall energetic status of the seminiferous tubule.

Role of GLP1-RA in Optimizing Weight Loss Post-Bariatric Surgery: A Systematic Review and Meta-Analysis.

Bariatric surgery is a widely used intervention for significant weight loss, yet some patients face challenges with insufficient weight loss or weight regain post-surgery. To address this issue, adjunctive treatments like glucagon-like peptide-1 receptor agonists (GLP1-RAs) are being explored for their potential to enhance weight loss outcomes. This meta-analysis was conducted to evaluate the effectiveness of GLP1-RAs in improving weight loss after bariatric surgery compared to a placebo. By systematically reviewing and analyzing data from three randomized controlled trials (RCTs) involving 130 patients, we found that GLP1-RA therapy, particularly liraglutide (1.8-3 mg), significantly reduced mean BMI and body weight percentage at six months. Future studies should explore newer GLP1-RAs with weekly dosing and include longer follow-up periods to assess the durability of these outcomes.

Liraglutide for the Treatment of Weight Regain After Bariatric Surgery: A Systematic Review and Meta-analysis.

INTRODUCTION: The efficacy of liraglutide for treating type 2 diabetes mellitus and obesity is well established, but their role in the treatment of weight regain after bariatric surgery remains unclear. METHODS: We searched PubMed, Embase, and Cochrane Library databases in January 2024. A random-effects model was employed to compute mean differences (MD) and events per 100 observations with 95% confidence intervals (CI) for continuous and binary endpoints. Statistical analysis was performed using R software. RESULTS: A total of 16 studies were included and 881 individuals. Patients were mostly female (50%), aged 36 to 55 years, with a mean body mass index (BMI) of 39.4 kg/m2, and had BS surgery 5 years prior. Over a mean follow-up time ranging from 3 months to 4 years, it was observed a statistically significant reduction in BMI (MD - 8.56 kg/m2; 95% CI 3.34 to 13.79; p < 0.01) and a mean reduction in total weight (MD - 16.03 kg; 95% CI 0.03 to 32.02; p = 0.05) after liraglutide use. Additionally, 65% of patients undertaking liraglutide showed total body weight loss (BWL) above 5% (65.8 events per 100 observations; 95% CI 54.96 to 75.20; p < 0.01), while 26% lost more than 10% of total BWL (26.77 events per 100 observations; 95% CI 19.17 to 36.02; p < 0.01). A limitation is a variability between the studies. CONCLUSIONS: Our findings support the use of liraglutide for weight management in patients who experience weight regain after BS. Liraglutide is well tolerated and promotes significant weight loss, providing clinicians with a therapeutic option for this clinical challenge.

Liraglutide for the treatment of weight regain after bariatric surgery: a systematic review and meta-analysis

INTRODUCTION: The efficacy of liraglutide for treating type 2 diabetes mellitus and obesity is well established, but their role in the treatment of weight regain after bariatric surgery remains unclear. METHODS: We searched PubMed, Embase, and Cochrane Library databases in January 2024. A random-effects model was employed to compute mean differences (MD) and events per 100 observations with 95% confidence intervals (CI) for continuous and binary endpoints. Statistical analysis was performed using R software. RESULTS: A total of 16 studies were included and 881 individuals. Patients were mostly female (50%), aged 36 to 55 years, with a mean body mass index (BMI) of 39.4 kg/m2, and had BS surgery 5 years prior. Over a mean follow-up time ranging from 3 months to 4 years, it was observed a statistically significant reduction in BMI (MD - 8.56 kg/m2; 95% CI 3.34 to 13.79; p < 0.01) and a mean reduction in total weight (MD - 16.03 kg; 95% CI 0.03 to 32.02; p = 0.05) after liraglutide use. Additionally, 65% of patients undertaking liraglutide showed total body weight loss (BWL) above 5% (65.8 events per 100 observations; 95% CI 54.96 to 75.20; p < 0.01), while 26% lost more than 10% of total BWL (26.77 events per 100 observations; 95% CI 19.17 to 36.02; p < 0.01). A limitation is a variability between the studies. CONCLUSIONS: Our findings support the use of liraglutide for weight management in patients who experience weight regain after BS. Liraglutide is well tolerated and promotes significant weight loss, providing clinicians with a therapeutic option for this clinical challenge.

Liraglutide Pretreatment Does Not Improve Acute Doxorubicin-Induced Cardiotoxicity in Rats.

Doxorubicin is an effective drug for cancer treatment; however, cardiotoxicity limits its use. Cardiotoxicity pathophysiology is multifactorial. GLP-1 analogues have been shown to reduce oxidative stress and inflammation. In this study, we evaluated the effect of pretreatment with liraglutide on doxorubicin-induced acute cardiotoxicity. A total of 60 male Wistar rats were allocated into four groups: Control (C), Doxorubicin (D), Liraglutide (L), and Doxorubicin + Liraglutide (DL). L and DL received subcutaneous injection of liraglutide 0.6 mg/kg daily, while C and D received saline for 2 weeks. Afterwards, D and DL received a single intraperitoneal injection of doxorubicin 20 mg/kg; C and L received an injection of saline. Forty-eight hours after doxorubicin administration, the rats were subjected to echocardiogram, isolated heart functional study, and euthanasia. Liraglutide-treated rats ingested significantly less food and gained less body weight than animals that did not receive the drug. Rats lost weight after doxorubicin injection. At echocardiogram and isolated heart study, doxorubicin-treated rats had systolic and diastolic function impairment. Myocardial catalase activity was statistically higher in doxorubicin-treated rats. Myocardial protein expression of tumor necrosis factor alpha (TNF-α), phosphorylated nuclear factor-κB (p-NFκB), troponin T, and B-cell lymphoma 2 (Bcl-2) was significantly lower, and the total NFκB/p-NFκB ratio and TLR-4 higher in doxorubicin-treated rats. Myocardial expression of OPA-1, MFN-2, DRP-1, and topoisomerase 2ß did not differ between groups (p > 0.05). In conclusion, doxorubicin-induced cardiotoxicity is accompanied by decreased Bcl-2 and phosphorylated NFκB and increased catalase activity and TLR-4 expression. Liraglutide failed to improve acute doxorubicin-induced cardiotoxicity in rats.

Liraglutide effectiveness in preoperative weight-loss for patients with severe obesity undergoing bariatric-metabolic surgery.

Preoperative management of patients living with severe obesity can be challenging; in this context, the preoperative weight loss may help to obtain better outcomes and less morbidity for bariatric surgery. Therefore, we evaluated the effectiveness of GLP-1 analogue Liraglutide in preoperative weight loss. We performed a single-center, quasi-experimental prospective study. Eligible participants were adults in preoperative management for bariatric-metabolic surgery with body-mass index ≥ 48 kg/m2. All patients were assigned liraglutide treatment, with an initial dose of 0.6 mg subcutaneous per day, the dose was increased each week until reaching 3.0 mg for 12 weeks. Weight loss and body composition were evaluated monthly using bioelectric impedance (BIA) (InBody 770 Scale®). We analyzed data using descriptive statistics, central tendency measures and dispersion for quantitative variables and absolute and relative frequencies for qualitative variables. A total of 37 individuals were included in this study, 28 (76%) were female and 9 (24%) were males, with an average age of 44 years. About the BMI, 19 patients (51%) had a BMI > 50 kg/m2, 10 (27%) > 40 kg/m2 and 8 (22%) > 60 kg/m2; with a total average BMI of 56.04 kg/m2. The initial weight was 147.4 ± 14.9 kg which decreased to 139.3 ± 16.8 kg; after 3 months of liraglutide administration. A total of 35 patients had some degree of weight loss (94.6%), while 2 (5.40%) had no weight changes. The total weight loss was 5.50% at 3 months of liraglutide treatment. Liraglutide could be an effective adjuvant therapy for preoperative weight loss in patients living with severe obesity.

Optimized LC-MS/MS method for quantifying insulin degludec and liraglutide in rat plasma and Tissues: Application in pharmacokinetics and biodistribution.

We present an ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous detection of insulin degludec (I-Deg) and liraglutide (LIRA) in rat plasma and tissues, characterized by its sensitivity and selectivity. Chromatographic separation was achieved using an Acquity UPLC BEH C18 column, leveraging a mobile phase of acetonitrile and water (both with 0.1 % formic acid) under gradient elution over a run time of 7.5 min. The mass spectrometer operated in positive electrospray ionization multiple reaction monitoring (MRM) mode, tracking transitions of m/z 1221.6 â†’ 641.6 for I-Deg, m/z 938.7 â†’ 1064.1 for LIRA, and m/z 1184.7 â†’ 454.4 for the internal standard. Validation ranged from 5 to 100 ng/mL, exhibiting robust linearity (r2 > 0.99) and limits of detection (LOD) of 1.63-2.02 ng/mL for I-Deg and 0.96-1.62 ng/mL for LIRA. Limits of quantification (LOQ) were 2.38-4.76 ng/mL for I-Deg and 3.22-4.40 ng/mL for LIRA. Notably, no significant matrix effects were detected. Stability was confirmed under various conditions, and precision metrics (intraday RSD 1.68-8.05 % for I-Deg and 1.11-7.69 % for LIRA; interday RSD 1.39-8.61 % for I-Deg and 1.06-8.83 % for LIRA) alongside accuracy (90.5-114.9 % for I-Deg and 92.7-113.7 % for LIRA) were within acceptable ranges. The method was successfully applied to pharmacokinetic and biodistribution studies following simultaneous subcutaneous administration of LIRA and I-Deg in rats.

Liraglutide modulates morpho-functional and inflammatory gastrointestinal responses in rats.

BACKGROUND: Obesity impairs homeostatic control of energy and is associated with chronic low-grade inflammation. Effects of glucagon-like peptide-1, the target in the gastrointestinal tract for anti-obesity drugs such as Liraglutide, were not properly associated with inflammation markers. This study investigated the effects of Liraglutide on metabolic and gastrointestinal parameters in a rat model of obesity. METHODS: Twenty-six Wistar rats with obesity were randomly distributed to receive saline (n = 10), 400 µg (n = 8), or 1200 µg of Liraglutide/kg/day (n = 8), subcutaneously for 30 consecutive days, once a day. Weight gain, feeding efficiency, caloric consumption, gastric motility, adiposity, histomorphometric, murinometric, biochemical parameters and cytokines TNF-α and TGF-ß1 in duodenal tissue were measured. Data were analysed by ANOVA, followed by Bonferroni post hoc or Kruskal-Wallis test, followed by Dunn's multiple comparison test. RESULTS: Liraglutide-treated animals had better feeding efficiency and higher caloric intake in a dose-dependent manner. Higher doses slowed gastric emptying and diminished the amplitude of gastric contractions. These effects were accompanied by decreases in intestinal muscle layer thickness and crypt depth. Liraglutide significantly reduced retroperitoneal and visceral white adipose tissue depots. High-dose treatment decreased levels of TNF-α and enhanced levels of TGF-ß1 in duodenal tissue. Liraglutide treatment provided significant reductions in total cholesterol, triglyceride and hepatic transaminases. CONCLUSIONS: Liraglutide reduced fat accumulation, improved metabolic parameters and downregulated levels of inflammatory signalling in duodenal tissue. Liraglutide at high doses controlled obesity-related outcomes, and such effects seemed to be driven by its action on glucagon-like peptide-1 receptors in the gastrointestinal tract slowing gastric motility.

The efficacy of liraglutide combined with intragastric balloon on weight loss.

OBJECTIVE: Intragastric balloon placement is an effective method for weight reduction. The aim of this study was to evaluate the efficacy of combining liraglutide with intragastric balloon. METHODS: Initially, demographic data of patients such as age, gender, comorbid diseases, adverse events, initial weight, height, body mass index, percent body fat, and waist-hip ratio were collected. Weight, body mass index, percent body fat, and waist-hip ratio were measured in the second, third, fourth, fifth, and sixth months. Then, intragastric balloon was removed and liraglutide was stopped. RESULTS: A total of 50 patients were included in the study, of whom 28 (56%) were in Group A (intragastric balloon) and 22 (44%) were in Group B (plus liraglutide). Weight change at the time of balloon removal was higher in Group B [median weight change 13.8 (7.8 min to 16.8 max) versus 7.9 (4.8 min to 11.8 max); p<0.01]. When the weight, percent body fat, body mass index, and waist-hip ratio changes were compared according to gender, no significant difference was observed in the groups. Comorbid diseases were hypertension in 7 patients (4 in Group A and 3 in Group B) and diabetes in 9 patients (5 in Group A and 4 in Group B). No statistical significance was found. CONCLUSION: Liraglutide has benefits in terms of weight, percent body fat, and body mass index reduction when administered with intragastric balloon.

Effect of liraglutide on cardiometabolic profile and on bioelectrical impedance analysis in patients with obesity and metabolic syndrome.

Metabolic syndrome (MetS) and obesity represent a public health problem worldwide. Bioelectrical impedance analysis (BIA) is a practical and effective way of evaluating body composition, especially abdominal fat. Liraglutide, a GLP-1 analog, reduces body weight and improves cardiometabolic parameters. In this prospective non-randomized intervention study, we evaluated the effect of 6 months of treatment with liraglutide (n = 57) on the clinical, laboratory and BIA findings of adult sex-stratified patients diagnosed with obesity and MetS, compared to a control group receiving sibutramine (n = 46). The groups were statistically similar with regard to the age of females (p = 0.852) and males (p = 0.657). Almost all anthropometric and BIA variables were higher in the treatment group than in the comparative group (p < 0.05). Abdominal circumference (AC) decreased significantly more in the treatment group. In males, body weight and fat mass also decreased (p < 0.05). Liraglutide treatment was associated with a greater reduction in trunk fat mass (FMT) (p < 0.05). AC and FMT were strongly correlated (rho = 0.531, p < 0.001) in the treatment group. In the multiple regression analysis, liraglutide treatment remained independently associated with FMT. Treatment with liraglutide for 6 months promoted weight loss, improved cardiometabolic and inflammatory parameters and led to a significant reduction in FMT correlated with AC in obese MetS patients of both sexes.

[Indicators of diabetes mellitus after liraglutide, sitagliptin/metformin, linagliptin, and sitagliptin]. / Indicadores de diabetes mellitus posterior a liraglutida, sitagliptina/metformina, linagliptina y sitagliptina.

Background: The control of diabetes mellitus is multifactorial, the different therapeutic options make it necessary to compare the effectiveness with previous therapeutic schemes. Objective: Analize the indicators of control of diabetes mellitus after incorporating liraglutide, sitagliptin/metformin, linagliptin, and sitagliptin. Methods: Observational, analytical, longitudinal study. Glucose, glycosylated hemoglobin, and blood pressure were compared after the inclusion of new cues in patients with diabetes mellitus; in addition to the control indicators reported in the unit in october, november, and december 2000, with those of 2021 in the same months. A descriptive analysis was performed, T for related samples and McNemar, a value of < .05 was considered significant, a confidence level of 95%, with the IBM-SPSS 24 software. Results: 352 files were analyzed, 59% women, aged 26 to 88 years, and the percentage of control decreased after the change of scheme (38.4% vs 35.8%) without a statistical difference (p .503). There was no statistical difference between the levels of glucose, glycated hemoglobin, weight, and blood pressure before and six months after the change. In the unit, the regimen glycemic control indicator improved in October, November, and December 2020 compared to the same months in 2021, it increased (from 17.2, 18.7, and 16.3, to 41.6, 47.2, and 46.5%). Blood pressure control went from 64.5, 66.7, and 67 to 82.4, 85.1, and 83.1%. Conclusions: The control indicators in the unit improved, however, the patients who used the new keys did not show any difference.

Introducción: el control de la diabetes mellitus es multifactorial, las diferentes opciones terapéuticas hacen necesario comparar la efectividad con esquemas terapéuticos previos. Objetivo: analizar los indicadores de control de diabetes mellitus posterior a incorporar liraglutida, sitagliptina/metformina, linagliptina y sitagliptina. Métodos: estudio observacional, analítico, longitudinal. Se compararon glucosa, hemoglobina glucosilada y presión arterial posterior a la inclusión de nuevas claves en pacientes con diabetes mellitus; además de los indicadores de control reportados en la unidad en los meses octubre, noviembre y diciembre 2020, con los del 2021 en los mismos meses. Se realizó un análisis descriptivo, T para muestras relacionadas y McNemar, se consideró un valor de p ≤ 0.05 como significativo, un nivel de confianza de 95%, con el programa informático IBM-SPSS 24. Resultados: se analizaron 352 expedientes, el 59% correspondía a mujeres, con edades de 26 a 88 años, el porcentaje de control disminuyó después del cambio de esquema (38.4% frente a 35.8%) sin diferencia estadística (p = 0.503). No hubo diferencia estadística entre los niveles de glucosa, hemoglobina glucosilada, peso y presión arterial previos y seis meses después del cambio de esquema. En la unidad, el indicador de control de glucemia en los meses de octubre, noviembre y diciembre 2020 comparados con los mismos meses en el 2021 incrementaron (17.2, 18.7 y 16.3, a 41.6, 47.2 y 46.5%). El control de presión arterial pasó del 64.5, 66.7 y 67 a 82.4, 85.1 y 83.1%. Conclusiones: los indicadores de control en la unidad mejoraron, sin embargo los pacientes que utilizaron las nuevas claves no mostraron diferencia.

Exogenous succinate impacts mouse brown adipose tissue mitochondrial proteome and potentiates body mass reduction induced by liraglutide.

Obesity is one of the leading noncommunicable diseases in the world. Despite intense efforts to develop strategies to prevent and treat obesity, its prevalence continues to rise worldwide. A recent study has shown that the tricarboxylic acid intermediate succinate increases body energy expenditure by promoting brown adipose tissue thermogenesis through the activation of uncoupling protein-1; this has generated interest surrounding its potential usefulness as an approach to treat obesity. It is currently unknown how succinate impacts brown adipose tissue protein expression, and how exogenous succinate impacts body mass reduction promoted by a drug approved to treat human obesity, the glucagon-like-1 receptor agonist, liraglutide. In the first part of this study, we used bottom-up shotgun proteomics to determine the acute impact of exogenous succinate on the brown adipose tissue. We show that succinate rapidly affects the expression of 177 brown adipose tissue proteins, which are mostly associated with mitochondrial structure and function. In the second part of this study, we performed a short-term preclinical pharmacological intervention, treating diet-induced obese mice with a combination of exogenous succinate and liraglutide. We show that the combination was more efficient than liraglutide alone in promoting body mass reduction, food energy efficiency reduction, food intake reduction, and an increase in body temperature. Using serum metabolomics analysis, we showed that succinate, but not liraglutide, promoted a significant increase in the blood levels of several medium and long-chain fatty acids. In conclusion, exogenous succinate promotes rapid changes in brown adipose tissue mitochondrial proteins, and when used in association with liraglutide, increases body mass reduction.NEW & NOTEWORTHY Exogenous succinate induces major changes in brown adipose tissue protein expression affecting particularly mitochondrial respiration and structural proteins. When given exogenously in drinking water, succinate mitigates body mass gain in a rodent model of diet-induced obesity; in addition, when given in association with the glucagon-like peptide-1 receptor agonist, liraglutide, succinate increases body mass reduction promoted by liraglutide alone.

Effectiveness, persistence of use, and safety of orlistat and liraglutide in a group of patients with obesity.

BACKGROUND: To determine the effectiveness, persistence of use, adverse reactions, interactions of orlistat and liraglutide taken for weight loss by a group of obese patients in Colombia. RESEARCH DESIGN AND METHODS: A retrospective follow-up study of a cohort of patients with obesity treated with orlistat or liraglutide. Sociodemographic, clinical, and pharmacological variables were identified. The effectiveness for weight loss at 12-16 and 52 weeks, persistence of use, and safety were determined. RESULTS: A total of 294 patients were followed up. At 12-16 weeks after starting orlistat and liraglutide, weight losses of -1.2kg (p=0.002) and -4.1kg (p<0.001) were observed, respectively, and at 52 weeks, reductions of -1.6kg (p=0.208) and -7.8kg (p<0.001) were observed. A total of 8.8% and 31.3% of patients treated with orlistat and liraglutide, respectively, persisted with treatment 1 year after initiation. A total of 17.3% had adverse drug reactions. Older adults with grade II or III obesity who performed physical activity and those treated with liraglutide were more likely to have lost at least 5% of their body weight at 12-16 weeks. CONCLUSION: Orlistat and liraglutide users presented weight loss at 12-16 weeks. However, this effect was greater and sustained with liraglutide, especially when combined with physical activity.

Protocolo Clínico e Diretrizes Terapêuticas (PCDT) de tratamento medicamentoso da obesidade em crianças e adolescentes com doze a vinte e um anos de idade no Estado de Goiás ­ versão janeiro de 2023 / Clinical Protocol and Therapeutic Guidelines (PCDT) for drug treatment of obesity in children and adolescents aged twelve to twenty-one years in the State of Goiás ­ January 2023 version

A obesidade é um transtorno crônico, complexo e multifatorial, envolve fatores ambientais, estilo de vida, hormonais e genéticos, acomete indivíduos de todas as idades e quanto mais cedo ocorre, maiores são os riscos à saúde. Uma criança com obesidade tem 80% chance de tornar-se um adulto com obesidade (FREEDMAN et al., 2007). Tratamento medicamentoso está aprovado a partir do IMC> 27 kg/m2 associado a comorbidades ou ≥ 30 kg/m2 mesmo na ausência de comorbidades. Liraglutida é o único medicamento aprovada para uso em adolescentes a partir dos 12 anos de idade com peso corporal maior que 60 kg e IMC correspondendo a 30 kg/m² para adultos

Liraglutida 3 mg para o tratamento de pacientes com obesidade e IMC acima de 35 kg/m², pré-diabetes e alto risco de doença cardiovascular / Liraglutide 3 mg for the treatment of patients with obesity and BMI above 35 kg/m², pre-diabetes and high risk of cardiovascular disease

INTRODUÇÃO: A obesidade é uma doença multifatorial altamente hereditária que representa um grande impacto na saúde humana. Ela pode ser definida como o acúmulo anormal ou excessivo de gordura, de forma regionalizada, generalizada ou ambas, que apresenta risco à saúde. Um índice de massa corporal (IMC) acima de 30 é considerado como obesidade, a qual pode ser classificada como leve (grau I; IMC ≥ 30 kg/m2 ), moderada (grau II; IMC ≥ 35 kg/m2 ) e grave (grau III; IMC ≥ 40 kg/m2 ). Dentre os fatores fisiológicos associados à obesidade, o Glucagon-like peptide-1 (GLP-1) se apresenta como um peptídeo chave, tendo como principais funções estimular a secreção de insulina dependente de glicose, reduzir o esvaziamento gástrico, melhorar a sensibilidade das células pancreáticas, inibir a liberação de glucagon e controlar a sensação de saciedade pela supressão da ingestão de alimentos e ingestão calórica. A liraglutida é um análogo do GLP-1 e apresenta homologia de 97% em relação à sequência de aminoácidos do GLP-1 huma

GLP-1 Agonist to Treat Obesity and Prevent Cardiovascular Disease: What Have We Achieved so Far?

PURPOSE OF REVIEW: To discuss evidence supporting the use of glucagon-like peptide 1 receptor agonists (GLP-1RA) to treat obesity and their role as a cardioprotective drug. Obesity is not just a hypertrophy of the adipose tissue because it may become dysfunctional and inflamed resulting in increased insulin resistance. Being overweight is associated with increased incidence of cardiovascular events and weight loss achieved through lifestyle changes lowers risk factors, but has no clear effect on cardiovascular outcomes. In contrast, treating obesity with GLP-1RA decreases cardiovascular risk and the possible mechanisms of cardioprotection achieved by this class of drugs are discussed. GLP-1RA were initially developed to treat type 2 diabetes patients, in whom the effects upon glycemia and, moreover, weight loss, especially with long-acting GLP-1RA, were evident. However, cardiovascular safety trials in type 2 diabetes patients, the majority presenting cardiovascular disease and excess weight, showed that GLP-1 receptor agonists were indeed capable of decreasing cardiovascular risk. RECENT FINDINGS: Type 2 diabetes treatment with GLP-1RA liraglutide and semaglutide paved way to a ground-breaking therapy specific for obesity, as shown with the SCALE 3 mg/day liraglutide program and the STEP 2.4 mg/week semaglutide program. A novel molecule with superior performance is tirzepatide, a GLP-1 and GIP (Gastric Inhibitory Peptide) receptor agonist and recent results from the SURPASS and SURMOUNT programs are briefly described. Liraglutide was approved without a CVOT (Cardiovascular Outcome Trial) because authorities accepted the results from the LEADER study, designed for superiority. The SELECT study with semaglutide will report results only in 2023 and tirzepatide is being tested in patients with diabetes in the SURPASS-CVOT. Clinical studies highlight that GLP-1RA to treat obesity, alongside their concomitant cardioprotective effects, have become a hallmark in clinical science.

Transitioning from basal-bolus or premix insulin therapy to a combination of basal insulin and glucagon-like peptide-1 receptor agonist in people with type 2 diabetes.

AIMS: Two fixed-ratio combinations (FRCs) of basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1RA) are available for once-daily use in adults with type 2 diabetes. We aimed to review the clinical evidence for the efficacy and safety of changing treatment from a basal-bolus insulin (BBI) regimen or a premix insulin to these combination treatments (fixed-ratio or loose) and provide expert opinion on the practicalities of making such a change. METHODS: Relevant clinical and trial evidence and general review articles were identified through a literature review of ProQuest (comprising BIOSIS Previews®, Current Contents® Search, Embase® and MEDLINE®) for articles published between 2009 and 2021. RESULTS: We identified nine articles reporting the results of FRCs, and seven articles reporting results of loose combinations of basal insulin and GLP-1RAs, in people who transitioned treatment from BBI or premix regimens. In most trials, combination treatment led to improved or equivalent glycaemic control, and a reduction in body weight or BMI, versus the original regimens. Some trials reported a reduction in total insulin dose. A few trials reported reduced or unchanged hypoglycaemia rates, or increased patient satisfaction, with combination therapy where these endpoints were examined. We provide guidance on transitioning of treatment and the patient types most likely to benefit. CONCLUSIONS: In people not achieving glycaemic control with BBI or premix insulin regimens, an FRC or loose combination of basal insulin and GLP-1RA may improve control, decrease the risk of body weight gain or hypoglycaemia and reduce the complexity of treatment.

Short-Term Effectiveness and Reduction in Insulin Requirements in Patients With Type 2 Diabetes Treated With IdegLira in a Real-World Setting.

Background: Type 2 diabetes mellitus (T2DM) is a chronic, highly prevalent disease with a significant impact on health. Appropriate treatment requires effective and timely escalation to achieve metabolic control. To evaluate the effectiveness and safety of IDegLira on adults with T2DM previously treated with oral antidiabetics and/or insulin in a real-life setting. Methods: An observational study in a real-world setting was conducted. Patients were selected from the outpatient clinic of two centers dedicated to specialized diabetes care. Main outcomes were HbA1c, body weight, insulin dose changes, hypoglycemia, and other adverse events. Results: 67 T2DM patients treated with IDegLira were monitored between 3 and 7 months. At the end of foll ow-up, the median change in HbA1c was -1.05% (CI95% -1.45, -0.65), and a decrease in insulin requirement was also observed (mean difference -10 TDD units (CI95% - 17 to -2.5). No treatment discontinuation was reported, hypoglycemia events were reported in 3 patients at the end of follow-up versus 8 patients at baseline. Conclusions: This real-life study shows the effectiveness in glycemic control of IDegLira use in T2DM patients who do not achieve goals with other therapies, with an adequate safety profile. The findings need to be confirmed with evaluation of therapeutic results in larger cohorts.

Liraglutida comparada a terapia padrão para o tratamento da obesidade: revisão rápida de evidências / Liraglutide compared to standard therapy for the treatment of obesity: rapid response review of evidence

Liraglutida e terapia padrão (modificação no estilo de vida, com dieta e prática regular de exercícios), como opção disponível no Sistema Único de Saúde. Indicação: Tratamento da obesidade. Pergunta: Liraglutida, comparada à terapia padrão, é mais eficaz e segura para promover redução do peso em pessoas adultas com obesidade? Métodos: Revisão rápida de evidências, revisão de revisões sistemáticas, com levantamento bibliográfico realizado na base de dados PUBMED, utilizando estratégia estruturada de busca. A qualidade metodológica das revisões sistemáticas foi avaliada com AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews version 2). Resultados: Foi selecionada uma revisão sistemática que atendeu aos critérios de inclusão. Conclusão: Liraglutida em dose ≤ 1,8 mg e em dose > 1,8 mg, comparadas a placebo (com terapia padrão) promoveram redução estatisticamente significativa de peso (-2,99 kg e -4,55 kg, respectivamente) e maior risco relativo de descontinuação do tratamento devido a efeitos adversos, com alta certeza de evidência para esses desfechos, além de maior risco relativo de náusea e de vômitos

Liraglutide and standard therapy (lifestyle modification, diet and regular exercise), as a option available in the Brazilian Public Health System. Indication: Treatment of obesity. Question: Is Liraglutide, compared to standard therapy, more effective and safer for weight reduction in obese adults? Methods: Rapid review of evidence, overview of systematic reviews, with a bibliographic search in the PUBMED database, using a structured search strategy. The methodological quality of systematic reviews was assessed with AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews version 2). Results: A unique systematic review that met the inclusion criteria was selected. Conclusion: Liraglutide at a dose ≤ 1.8 mg and at a dose > 1.8 mg, compared to placebo (and standard therapy) induced statistically significant weight reduction (-2.99 kg and -4.55 kg, respectively) and greater relative risk of treatment discontinuation due to adverse effects, with high certainty of evidence, and greater relative risk of nausea and vomiting