Safety Of Liraglutide Research Articles

The Efficacy and Safety of Liraglutide in Patients Remaining Obese 6 Months after Metabolic Surgery.

The safety and efficacy of liraglutide as a weight loss intervention in individuals who remain obese within 1year post-metabolic surgery remain unclear. This study aimed to evaluate the effects and safety of liraglutide (1.8mg) in patients with persistent obesity at 6months postoperatively. This retrospective cohort study included 61 patients who remained obese (body mass index [BMI] ≥ 28.0kg/m2) at 6months postoperatively. Among these patients, 27 were treated with 1.8mg of liraglutide for 12weeks, whereas 34 served as controls. The primary endpoint was the change in total weight loss (%TWL) after 24weeks. Changes in weight, BMI, complications, and adverse events were also assessed. The liraglutide group showed a greater reduction in %TWL than the control group (11.6% ± 1.1% vs. 4.9% ± 1.0%), with an estimated treatment difference of 6.6% (95% confidence interval [CI], 3.7-9.6%, P < 0.01). The adjusted mean differences in the reduction of weight and BMI between the liraglutide and control groups were -6.2kg (95% CI -8.9 to -3.4, P < 0.01) and -3.0kg/m2 (95% CI -4.2 to -1.7, P < 0.01), respectively. The liraglutide group exhibited increased rates of remission in non-alcoholic fatty liver disease and hypertension. No serious adverse reactions were observed. For patients who remained obese at 6months postoperatively, 12-week liraglutide treatment resulted in increased weight loss, improved metabolic control, and high rate of remission for obesity-related metabolic diseases after 24weeks. Earlier and more timely adjuvant weight loss medication intervention based on BMI within 1year postoperatively may enhance weight loss after metabolic surgery. Graphical abstract available for this article.

GLP-1 and GIP analogues in the treatment of obesity

Obesity is a chronic disease and a significant public health problem. It is estimated that more than 650 million adults, 340 million adolescents, and 39 million children are obese. Obesity leads to organ complications including type 2 diabetes, hypertension and heart diseases. The management of obesity is based on nutritional therapy combined with lifestyle changes and increased physical activity. Pharmacotherapy is also crucial, and incretin analogues are a relatively new group of drugs. Glucose-independent insulinotropic peptide and glucagon-like peptide-1 are natural incretins. These short half-life hormones are degraded by the enzyme dipeptidyl peptidase-4. Glucose-independent insulinotropic peptide and glucagon-like peptide-1 receptor agonists increase blood glucose-dependent insulin secretion while inhibiting glucagon secretion and delaying gastric emptying, thus enabling the treatment of both type 2 diabetes and obesity. Glucagon-like peptide-1 also exhibits cardioprotective and neuroprotective effects. This study aimed to review the literature on the use of glucagon-like peptide-1 analogues and verify reports on the use of glucose-dependent insulinotropic polypeptide for weight reduction. An analysis of the available literature on the efficacy and safety of liraglutide, semaglutide and tirzepatide was conducted. The potential role of these drugs in weight reduction and possible adverse effects are discussed. Attention was also paid to the pharmacokinetics of the drugs and the mechanism of incretin action in the body.

Efficacy and Safety of Liraglutide in Patients With an Ileal Pouch-Anal Anastomosis and Chronic High Bowel Frequency: A Placebo-Controlled, Crossover, Proof-of-Concept Study.

After colectomy with ileoanal pouch anastomosis (IPAA), many patients develop high bowel frequency (BF) refractory to antimotility agents, despite normal IPAA morphology. Low circulating levels of glucagon-like protein-1 (GLP-1), a modulator of gastroduodenal motility, have been reported after colectomy. Double-blind crossover study of 8 IPAA patients with refractory high BF treated with daily administration of the GLP-1 receptor agonist liraglutide or placebo. Liraglutide, but not placebo, reduced daily BF by more than 35% ( P < 0.03). Larger randomized controlled studies are warranted to delineate the treatment potential of GLP-1 receptor agonists in IPAA patients suffering from noninflammatory high BF.

FRI075 Single Center Retrospective Matched Cohort Study Of glp1ra-induced Weight Loss In Patients With Post-bariatric Weight Regain Vs Non-surgical Controls

Abstract Disclosure: A. Rivadeneira: None. M. Walker: None. R. Gallop: None. A. Amaro: Advisory Board Member; Self; Novo Nordisk. Research Investigator; Self; Eli Lilly &amp; Company, Novo Nordisk. Background: Obesity prevalence worldwide is increasing. By 2030, almost one-fourth of US population will have severe obesity (BMI &amp;gt;35 mg/kg2). Bariatric surgery (BS) is an effective intervention for weight loss (WL) in patients with severe obesity; weight regain (WR) remains a concern. Over one-third of patients will regain more than 25% of total WL. GLP-1 receptor agonists (GLP1RA) have been effective for WL in patients with obesity. Effectiveness and safety of liraglutide and semaglutide in patients with WR after BS were observed in several retrospective studies. The difference in response to GLP1RA in patients with and without a history of bariatric surgery has not been assessed. Objectives: We aimed to retrospectively compare amount of WL and time to nadir in BMI matched individuals with history of WR following BS and without history of surgery treated with GLP1RA. Methods: Retrospective matched cohort study of the patients referred to Penn Metabolic Medicine (PMM) clinic for non-surgical weight management. We analyzed 63 patients with history of RYGB or VSG seen between 8/2015-8/2021 for WR and who received GLP1RA. BMI matched non-surgical (NS) cohort (N=60) treated with GLP1RA was built from the PMM patients of the same period for comparison. Results: Mean weight on presentation at PMM in surgical group (SG) was 273.1 lbs, (BMI 43.5 kg/m2), and in non-surgical one (NS) 264.9 lbs (BMI 43.3 kg/m2). Nadir weight after initiation of GLP1RA in SG 241.1 lbs and controls 244 lbs, with percentage WL of 11.8% in SG and 7.86% in NS controls (p-value 0.0081). Mean time to nadir weight after initiation of GLP1RA was 17.2 months for SG, and 9.2 months in NS controls (p-value &amp;lt;0.0001). Discussion: When treated with GLP1RA, patients with post-bariatric WR lost on average 12% of their weight and achieved nadir around 17 months. Weight matched NS controls lost less weight and entered a plateau phase faster, suggesting enhanced GLP1RA efficacy after bariatric surgery. Significant WL response to GLP1RA was similar in RYGB and VSG groups, supporting previously demonstrated GLP1RA efficacy for post-bariatric WR. Larger prospective trials are needed for confirmation. Reports suggest both RYGB and VSG increase postprandial GLP-1. Proposed WR mechanisms include hormonal changes, nutritional non-adherence, physical inactivity and maladaptive eating. Hormonal mechanisms include increase in ghrelin, decrease in GLP-1 and peptide YY, post-bariatric hypoglycemia and other pathways. Further studies are needed to elucidate the mechanism of enhanced GLP-1 RA efficacy in patients with WR after BS. The limitations of our study include a retrospective nature, modest sample size and the choice of GLP1RA limited to liraglutide, exenatide and semaglutide and guided by the subjects’ insurance plans. In the future, dual incretins will need to be studied in patients with WR after bariatric surgery. Presentation: Friday, June 16, 2023

Laparoscopic adjustable gastric banding with liraglutide in adults with obesity and type 2 diabetes (GLIDE): a pilot randomised placebo controlled trial

IntroductionObesity drives type 2 diabetes (T2DM) development. Laparoscopic adjustable gastric banding (LAGB) has lower weight reduction than other bariatric procedures. Liraglutide, a GLP-1 receptor agonist, improves weight and glycaemic control in patients with T2DM. This study aimed to determine the efficacy and safety of liraglutide 1.8 mg in participants undergoing LAGB.MethodsGLIDE, a pilot randomised, double-blind, placebo-controlled trial, evaluated LAGB with either liraglutide 1.8 mg or placebo in participants with T2DM and obesity. Participants were randomised (1:1) to 6-months therapy post-LAGB, with further 6 months off-treatment follow-up. The primary outcome was change in HbA1c from randomisation to the end of treatment, secondary outcomes included body weight change. A sample size of 58 (29 per group) had 80% power to detect a 0.6% difference in HbA1c between groups.ResultsTwenty-seven participants were randomised to liraglutide (n = 13) or placebo (n = 14). Multivariate analysis showed no difference between placebo and liraglutide arms in HbA1c at 6 months (HbA1c:0.2 mmol/mol, −11.3, 11.6, p = 0.98) however, at 12 months HbA1c was significantly higher in the liraglutide arm (HbA1c:10.9 mmol/mol, 1.1, 20.6, p = 0.032). There was no difference between arms in weight at 6 months (BW:2.0 kg, −4.2, 8.1, p = 0.50), however, at 12 months weight was significantly higher in the liraglutide arm (BW:8.2 kg, 1.6, 14.9, p = 0.02). There were no significant differences in adverse events between groups.ConclusionsOur pilot data suggest no additional improvement in glycaemic control or BW with LAGB and liraglutide therapy. However, this trial was significantly underpowered to detect a significant change in the primary or secondary outcomes. Further trials are needed to investigate whether GLP-1 agonists, and particularly with more effective weekly agents (i.e. semaglutide or tirzepatide), are of benefit following metabolic surgery.Clinical trial registrationEudraCT number 2015-005402-11.

Use of liraglutide in the patient with obesity and type 2 diabetes mellitus: a literature review

Obesity and type 2 diabetes mellitus represent two of the most pressing public health challenges globally. In recent decades, an alarming increase in the prevalence of both conditions has been observed, which has led to a significant increase in the burden of disease and an increased search for effective therapeutic strategies. As evidence accumulates on the efficacy and safety of Liraglutide in this patient population, a comprehensive review of the available scientific literature is necessary. The objective of this literature review is to analyze and synthesize relevant studies investigating the use of liraglutide in patients with obesity and type 2 diabetes mellitus, in order to provide a comprehensive view on its effectiveness, indications, complications and management. In conclusion, the use of liraglutide in patients with obesity and type 2 diabetes mellitus has been shown to be an effective therapeutic option to improve glycemic control, promote weight loss and reduce cardiovascular risk. This drug, as a GLP-1 receptor agonist, stimulates insulin secretion, suppresses excessive glucagon release and delays gastric emptying, which contributes to the improvement in glycemic control.

Effectiveness and tolerability of liraglutide for the management of weight regain following sleeve gastrectomy.

There is currently very little research evidence on the benefits and safety of liraglutide in the management of weight regain or inadequate weight loss following metabolic and bariatric surgery. This study aimed to determine the clinical effectiveness and tolerability of liraglutide as an adjunct therapy for managing weight regain and inadequate weight loss following sleeve gastrectomy (SG). This was a retrospective analysis of medical records conducted at a private clinic in Kuwait. Data of 57 post-SG patients were included in the analysis. The mean (±SD) pre-treatment weight was 96.12 (29.26) kg. Following a median liraglutide treatment duration of approximately 3months, the mean post-treatment weight was 90.19 (26.82) kg. This represents a statistically significant mean weight loss of 5.94 (6.31) kg (p<0.001), corresponding to a loss of 6.20% of pre-treatment weight. Patients aged 31-40years achieved a greater post-treatment weight loss of 7.63 (7.41) kg, a loss of 7.80%, relative to age groups after treatment (p=0.047). Patients who tolerated ≥2.4mg of liraglutide recorded a higher mean weight loss of 8.42 (7.63) kg, a loss of 8.10% (p=0.010). The use of liraglutide may be an effective adjunct treatment for weight optimization following SG. Maximizing the tolerable dose may yield greater weight reduction.

New Insights into the Use of Liraglutide-Impact on Cardiovascular Risk and Microvascular Outcomes.

Despite the availability of many glucose-lowering drugs, patients with type 2 diabetes mellitus (T2DM) often do not achieve the desired effect, and cardiovascular complications remain the leading cause of death in this group of patients. Recently, more and more attention has been paid to the properties of drugs, with particular emphasis on the possibility of reducing cardiovascular risk. One of them is liraglutide, which belongs to long-acting analogs of glucagon-like peptides-1 (GLP-1); it imitates incretins and causes an increase in insulin secretion. The current study focused on analyzing the efficacy and safety of liraglutide, as well as its impact on microvascular and cardiovascular outcomes in the treatment of patients with T2DM. Hyperglycemia-induced endothelial dysfunction, which is known to play a key role in maintaining cardiovascular homeostasis, is common in diabetes. Liraglutide reduces endothelial dysfunction by reversing damage to endothelial cells. By reducing the generation of reactive oxygen species (ROS), thereby affecting Bax, Bcl-2 protein levels, and restoring signaling pathways, Liraglutide reduces oxidative stress, inflammation, and prevents endothelial cell apoptosis. Liraglutide has beneficial effects on the cardiovascular system; patients with high cardiovascular risk particularly benefit from treatment, as it reduces their major adverse cardiovascular event (MACE) rate, which takes into account cardiovascular death, stroke, and non-fatal myocardial infarction. Liraglutide reduces the occurrence and progression of nephropathy, which is one of the most common microvascular complications of diabetes.

Comparing the bioequivalence and safety of liraglutide in healthy Chinese subjects: an open, single-dose, randomized, repeated, two-sequence, two-cycle phase I clinical trial

ABSTRACT Background Glucagon-like peptide-1 (GLP-1) is an endogenous incretin hormone. Liraglutide, a GLP-1 receptor agonist, can lower blood sugar by increasing insulin production and inhibiting the production of glucagon. This study researched the bioequivalence and safety of the test and reference drugs in healthy Chinese subjects. Research design and methods Subjects (N = 28) were randomly divided into group A and group B at a ratio of 1:1 for a two-cycle cross-over study. There was single dose per cycle with subcutaneous injection of the test and reference drugs, respectively. The washout was set at 14 days. Plasma drug concentrations were detected by specific liquid chromatography and tandem mass spectrometry (LC-MS/MS) assays. Statistical analysis of major pharmacokinetic (PK) parameters was conducted to assess drug bioequivalence. In addition, we evaluated the safety of the drugs throughout the trial. Results The geometric mean ratios (GMRs) of Cmax, AUC0-t, and AUC0-∞ for the test and reference drugs were 107.11%, 106.56%, 106.09%, respectively. The 90% confidence intervals (CIs) were all within 80%-125%, meeting the bioequivalence standards. In addition, both had good safety in this study. Conclusion The study shows that the two drugs had similar bioequivalence and safety. Clinical trial registration DCTR: CTR20190914; ClinicalTrials.gov: NCT05029076

Efficacy and safety of liraglutide in patients with type 2 diabetes mellitus and severe obstructive sleep apnea

ObjectivesTo observe the efficacy and side effects of liraglutide in the treatment of type 2 diabetes mellitus (T2DM) patients with severe obstructive sleep apnea (OSA).MethodsThe study conducted in an outpatient setting was a two-center, prospective randomized controlled study. T2DM patients with severe OSA were randomized to the control group (continuous positive airway pressure [CPAP] and drug treatment without liraglutide) or the liraglutide group (CPAP and drug treatment including liraglutide). Demographic and clinical characteristics, sleep-disordered breathing indices, cardiac function indices, and side effects were evaluated and compared between the two groups before and after 3 months.ResultsOf 90 patients, 45 were randomized to the intervention arm (with liraglutide) and 45 to the control arm (without liraglutide). One patient in the liraglutide group dropped out of the study on day 8 after enrollment due to obvious gastrointestinal symptoms. No significant differences were found between the two groups in baseline demographics, clinical characteristics, cardiac function indicators, or sleep disorder respiratory indices (P > 0.05). After 3 months, the body mass index (BMI), apnea hypopnea index (AHI), and mean systolic blood pressure in the liraglutide treatment group were significantly lower than those in the control group (P < 0.05). The minimum oxygen saturation was significantly higher in the liraglutide group compared with that in the control group after 3 months of follow-up (P < 0.05). No difference was found between the two groups in the summary of side effects (P > 0.05).ConclusionsLiraglutide combined with CPAP can effectively reduce BMI, lower mean systolic blood pressure, and improve AHI scores and hypoxia in T2DM patients with severe OSA. Liraglutide did not increase side effects.

Efficacy and Safety of Liraglutide and Semaglutide on Weight Loss in People with Obesity or Overweight: A Systematic Review.

The effect and safety of Semaglutide and Liraglutide on weight loss in people with obesity or overweight were evaluated by a Network Meta-Analysis system to provide an evidence-based reference for clinical treatment. Computer searched PubMed, Embase, and Cochrane Library databases to collect Liraglutide and Semaglutide injection monotherapy RCTs until April 2022, using Stata 16 software for Network Meta-Analysis. Twenty-three RCTs study with 11,545 patients and 4 interventions (semaglutide 2.4mg, semaglutide 1.0mg, liraglutide 3.0mg and liraglutide 1.8 mg) were finally included. In terms of efficacy, semaglutide 2.4mg (-12.47 kg) had the best weight loss, followed by liraglutide 3.0mg (-5.24 kg), semaglutide 1.0mg (-3.74 kg) and liraglutide 1.8mg (-3.29 kg). In terms of decreased HbA1c, semaglutide 2.4mg (MD=-1.48%, 95% CI [-1.93, -1.04]), semaglutide 1.0mg (MD=-1.36%, 95% CI [-1.72, -1.01]), liraglutide 1.8mg (MD=-1.23%, 95%Cl [-1.66, -0.80]) more effective than placebo. In terms of safety, the total incidence of adverse events was semaglutide 2.4mg > liraglutide 3.0mg > liraglutide 1.8mg > semaglutide 1.0mg compare to placebo, the incidence of serious adverse events was liraglutide 3.0mg > liraglutide 1.8mg > semaglutide 2.4mg > semaglutide 1.0mg, the incidence of hypoglycemic events was semaglutide 2.4mg > liraglutide 3.0mg > semaglutide 1.0mg > liraglutide 1.8mg. This meta-analysis indicates that all GLP-1RAs were more efficacious than placebo in people with obesity or overweight on efficacy. Semaglutide 2.4mg has an absolute advantage in weight loss and decreased HbA1c, but the incidence of total adverse events is also the highest and can cause hypoglycemia. In addition, although liraglutide 3.0mg was less effective than semaglutide 2.4mg, serious adverse events were still the most elevated.

Efficacy and Safety of Liraglutide 3.0 mg in Patients with Overweight and Obese with or without Diabetes: A Systematic Review and Meta-Analysis.

Background Liraglutide in a 3.0 mg subcutaneous dose daily is approved for weight reduction. Objectives Objectives are to evaluate the efficacy and safety of liraglutide 3.0 mg in patients with overweight and obesity irrespective of diabetic status. Methods We conducted an electronic database search in PubMed, Embase, and https://ClinicalTrial.gov to identify all randomized control trials (RCTs) that evaluated the efficacy and safety of liraglutide 3.0 mg dose compared to placebo in overweight (≥27 kg/m2) and obese (≥30 kg/m2) patients above 18 years of age. Results We compared the pooled estimate of the study results between liraglutide 3.0 mg groups and placebo groups both in diabetic and nondiabetic patients. The efficacy outcomes that were found to be significant among respective studies involving nondiabetic patients vs. diabetic patients were mean change in body weight from baseline: 12 studies [MD = −5.04 kg (95% CI = −5.60, −4.49), P < 0.001, I2 = 92.95%] vs. 2 studies [MD = −4.14 kg (95% CI = −4.95, −3.32), P < 0.001, I2 = 0%], reduction in waist circumference from baseline: 8 studies [MD = −3.64 cm (95% CI = −4.43, −2.85), P < 0.001, I2 = 96.5%] vs. 2 studies [MD = −3.11 cm (95% CI = −3.88, −2.34), P < 0.001, I2 = 0%], BMI reduction from baseline: 5 studies [MD = −1.95 kg/m2 (95% CI = −2.22, −1.68) vs. 1 study [MD = −1.86 kg/m2 (95% CI = −2.14, −1.57), P < 0.001, I2 = 0%, P < 0.001, I2 = 95.6%], proportion of patients losing more than 5% of weight loss from baseline: 8 studies [RR = 2.21, (95% CI = 1.89, 2.58), P=0.03, I2 = 59.02%] vs. 2 studies [RR = 2.34, (95% CI = 1.93, 2.85), P=0.39, I2 = 0.00%], and 10% weight loss from baseline: 7 studies [RR = 3.36, (95% CI = 1.92, 5.91), P=0.00, I2 = 87.03%] vs. 2 studies [RR = 3.64, (95% CI = 2.46, 5.40), P=0.81, I2 = 0.00%]. Safety outcome assessment with use of liraglutide 3.0 mg compared with placebo in respective nondiabetic vs. diabetic patients revealed significant proportion of patients experiencing the adverse events: 9 studies [RR = 1.11, (95% CI = 1.04, 1.18), P=0.00I2 = 79.15%] vs. 2 studies [RR = 1.06, (95% CI = 1.01, 1.11), P=0.42, I2 = 0.03%] but similar risk of serious adverse events: 9 studies [RR = 1.03, (95% CI = 0.70, 1.51), P=0.26, I2 = 18.54%] vs. 2 studies [RR = 1.11, (95% CI = 0.67, 1.84), P=0.25, I2 = 23.77%] and TDAEs: 4 studies [RR = 0.89, (95% CI = 0.35, 2.28), P=0.03, I2 = 61.89%] vs. 1 study [RR = 2.53, (95% CI = 1.00, 6.37)]. However, the pooled estimates irrespective of the glycaemic status were mean change in body weight from baseline: 14 RCT [MD = −4.91 kg (95% CI = −5.43, −4.39), P < 0.001, I2 = 92.35%], reduction in waist circumference from baseline: 10 studies [MD = −3.55 cm, (95% CI = −4.21, −2.89), P < 0.001, I2 = 94.99%], BMI reduction from baseline: 6 studies [MD = −1.86 kg/m2, (95% CI = −2.14, −1.57), P < 0.001, I2 = 96.14%], and proportion of patients losing more than 5% and 10% of weight from baseline: [RR = 2.23, (95% CI = 1.98, 2.52), P < 0.001, I2 = 48.87%] and [RR = 3.28, (95% CI = 2.23, 4.83), P < 0.001, I2 = 78.98%], respectively. Also, the proportion of patients experiencing the adverse event was more with liraglutide 3.0 mg compared with placebo 11 study [RR = 1.09, (95% CI = 1.04, 1.15), P < 0.01, I2 = 76.60%] and similar risk for both serious adverse events: 11 studies [RR = 1.09, (95% CI = 1.04, 1.15), P < 0.01, I2 = 76.60%] and TDAEs: 5 studies [RR = 1.14, (95% CI = 0.50, 2.60), P < 0.01, I2 = 64.93%] with liraglutide compared with placebo. Conclusions Liraglutide in 3.0 mg subcutaneous dose demonstrated significant weight reduction with a reasonable safety profile for patients with overweight or obesity regardless of diabetic status compared to placebo.

Efficacy of liraglutide 3.0 mg treatment on weight loss in patients with weight regain after bariatric surgery

PurposeBariatric surgery, as Roux-en-Y gastric bypass (RYGB), laparoscopic gastric banding (LGB), and laparoscopic sleeve gastrectomy (LSG), is considered the gold standard treatment to achieve long-term weight loss in severe obesity. In patients who fail to maintain the achieved weight, pharmacological treatment may be required. Here, we reported our real-life experience on the efficacy of liraglutide therapy in 62 patients who regained weight after bariatric surgery.MethodsWe retrospectively evaluated 62 (60 F-2 M; mean age: 43.6 ± 9.9 years) patients received liraglutide for weight loss after bariatric surgery (17 RYGB, 22 LGB, and 23 LSG). Body mass index (BMI) before and after surgery was, respectively, of 45.4 ± 5.5 kg/m2 and 29.5 ± 4.9 kg/m2. Patients were followed up from 2016 until 2021. Liraglutide was administered after weight regain once-daily subcutaneously at starting dose of 0.6 mg and with weekly increases up to 3.0 mg. Treatments were administered when a weight regain of 10–15% occurred after reaching a minimum weight loss from bariatric surgery or if weight loss after bariatric surgery was unsatisfactory.ResultsAfter a mean of 70.7 ± 43.7 months from any bariatric surgery, all patients started liraglutide therapy. At this time, mean BMI was 34.2 ± 4.8 kg/m2 (mean increased BMI: 4.7 ± 2.8 kg/m2). After a mean of 10.5 ± 4.4 months from the beginning of liraglutide, 9 patients achieved normal weight (BMI 24.1 ± 0.9 kg/m2), and 28 were overweight (BMI 26.9 ± 1.6 kg/m2). Twenty patients achieved grade I (BMI 32.1 ± 1.5 kg/m2), 5 grade II (BMI 37.3 ± 2.0 kg/m2) obesity, and none had grade III obesity (mean BMI change: − 5.1 ± 2.5 kg/m2). The treatment was well tolerated, and no serious adverse events were recorded.ConclusionThese data confirm the efficacy and safety of liraglutide in patients who experienced weight regain after bariatric surgery. Considering the long-term follow-up, patients should be followed up regularly and the pharmacological treatment should be adapted to the weight fluctuations observed during the clinical history.Level of evidenceV. Opinions of authorities, based on descriptive studies, narrative reviews, clinical experience, or reports of expert committees.

Effectiveness and Safety of Liraglutide in Managing Inadequate Weight Loss and Weight Regain after Primary and Revisional Bariatric Surgery: Anthropometric and Cardiometabolic Outcomes.

No study appraised the effectiveness and safety of liraglutide in managing inadequate weight loss or weight regain (IWL/ WR) after primary versus revisional bariatric surgery (BS). Retrospective study of all eligible adults who completed liraglutide 3mg therapy for IWL/WR after primary or revisional BS at our institution between May 2016 and June 2019 (N = 145; 119 primary, 82%; 26 revisional, 18%). Changes in anthropometric and cardiometabolic parameters were assessed before the start of liraglutide and at 6 and 12months after treatment. The mean age was 43.32 ± 10.49years, and 83% were females. Patients received liraglutide at a meanof 54.10 ± 31.75months after their BS, for WR (74.3%) or IWL (25.6%). Liraglutide significantly reduced weight and BMI among primary and revisional patients (P < 0.0001 for all) and was equally effective in these reductions for both groups. Primary patients achieved total weight loss percentage (TWL%) of 5.97% and 6.93% at 6 and 12months. Additionally, 52.3% and 60% of the patients lost ≥ 5% of their total weight (TW) at 6 and 12 months after primary BS. Revisional patients achieved TWL% of 6.41% and 4.99% at 6 and 12months, and 60% and 48% of patients lost ≥ 5% TW at the two time points. Liraglutide did not improve cardiometabolic outcome for primary patients; for revisional patients, only the systolic blood pressure decreased after treatment. Liraglutide was well tolerated, and the most common side effect was nausea. Liraglutide is useful as an adjunct weight loss medication for patients achieving unsatisfactory outcomes with BS.

Withdrawal: "Efficacy and safety of liraglutide 3.0 mg in obese diabetic and non-diabetic patients-A systematic review and meta-analysis of randomised controlled trials" Mahanjit Konwar, Renju Ravi, Miteshkumar Maurya, Debdipta Bose, Sanjeet kumar Jaiswal.

"This article was published whilst it was still in peer review due to a technical error at the publisher and has been temporarily removed."

The Efficacy and Safety of Liraglutide 3.0 mg for Weight Management in Obese Non-Diabetic Saudi Outpatients.

BackgroundUnmanaged cases of obesity might lead to serious conditions and complications, which impair patients’ lives. The aim of this study was to assess the effectiveness and safety of daily 3 mg subcutaneous (s/c) Liraglutide amongst obese non-diabetic patients in Eastern Province, Saudi Arabia.MethodsA retrospective cohort study of obese non-diabetic Saudi patients with obesity managed with s/c Liraglutide 3.0 mg who visited the outpatient clinic in Al Mashfa Hospital, Al Khobar, KSA during 2019–2021. We collected patient data from the electronic reporting system for different parameters. Body weight, hemoglobin A1c %, systolic and diastolic blood pressure mmHg were obtained at baseline and after the intervention.ResultsRecords of 258 patients who were using a daily dose of Liraglutide 3.0 mg s/c for at least four months have been reviewed. The body weight loss of patients who used Liraglutide for four months was 8.1±0.8 kg. Moreover, around 204 patients continued for up to six months. Meanwhile, the mean body weight loss was 13 kg. There was a significant reduction of hemoglobin A1c (HbA1c) % by 0.43%. The majority of patients (94.5%) reported satisfaction with the treatment, while adverse events were mainly nausea, vomiting and constipation.ConclusionDaily s/c Liraglutide of 3.0 mg is effective in producing significant body weight reduction in obese non-diabetic Saudi patients with tolerable minimal side effects and may provide health benefits in terms of reduced risk of obesity and its related outcomes.

Liraglutide changes body composition and lowers added sugar intake in overweight persons with insulin pump-treated type 1 diabetes.

To present secondary outcome analyses of liraglutide treatment in overweight adults with insulin pump-treated type 1 diabetes (T1D), focusing on changes in body composition and dimensions, and to evaluate changes in food intake to identify potential dietary drivers of liraglutide-associated weight loss. A 26-week randomized placebo-controlled study was conducted to investigate the efficacy and safety of liraglutide 1.8mg daily in 44 overweight adults with insulin pump-treated T1D and glucose levels above target, and demonstrated significant glycated haemoglobin (HbA1c)- and body weight-reducing effects. For secondary outcome analysis, dual X-ray absorptiometry scans were completed at Weeks 0 and 26, and questionnaire-based food frequency recordings were obtained at Weeks 0, 13 and 26 to characterize liraglutide-induced changes in body composition and food intake. Total fat and lean body mass decreased in liraglutide-treated participants (fat mass -4.6kg [95% confidence interval {CI} -5.7; -3.5], P< 0.001; lean mass -2.5kg [95% CI -3.2;-1.7], P< 0.001), but remained stable in placebo-treated participants (fat mass -0.3kg [95% CI -1.3;0.8], P= 0.604; lean mass 0.0kg [95% CI -0.7;0.7]; P= 0.965 [between-group P values <0.001]). Participants reduced their energy intake numerically more in the liraglutide arm (-1.1MJ [95% CI -2.0;-0.02], P= 0.02) than in the placebo arm (-0.9MJ [95% CI -2.0;0.1], P= 0.22), but the between-group difference was statistically insignificant (P= 0.42). However, energy derived from added sugars decreased by 27% in the liraglutide arm compared with an increase of 14% in the placebo arm (P= 0.004). Liraglutide lowered fat and lean body mass compared with placebo. Further, liraglutide reduced intake of added sugars. However, no significant difference in total daily energy intake was detected between liraglutide- and placebo-treated participants.

The effectiveness and safety of liraglutide in treating overweight/obese patients with polycystic ovary syndrome: a meta-analysis.

The purpose of this study is to evaluate the effectiveness and safety of liraglutide/liraglutide + metformin in overweight/obese women with polycystic ovary syndrome (PCOS). The related literatures published until April 2021 were searched in PubMed, Cochrane Library, MEDLINE and EmBase. Six randomized controlled trials of 127 related articles were obtained through searching. Three articles compared liraglutide with metformin, and four articles compared liraglutide combined with metformin with metformin. Our meta-analysis suggests that liraglutide was superior to metformin only in weight loss [MD = -2.74, 95% CI (-4.29, -1.18), P = 0.0006]. Compared with metformin group, the combination group had significant advantages in weight loss [MD = -3.81, 95% CI (-5.16, -2.46), P < 0.001], BMI [MD = -2.59, 95% CI (-3.12, -2.07), P < 0.001], waist circumference [MD = -6.26, 95% CI (-7.79, -4.72), P < 0.001], fasting blood glucose [MD = -0.59, 95% CI (-0.74, -0.44), P < 0.001] and fasting insulin [MD = -1.52, 95% CI (-2.69, -0.35), P = 0.01], while the incidence of adverse reactions was relatively high [RR = 2.91, 95% CI (1.55, 5.46), P = 0.00009]. The present results indicate that liraglutide and metformin have the similar effects in the treatment of overweight/obese PCOS patients. Liraglutide combined with metformin is more effective than metformin in improving PCOS, but it is necessary to master the correct medication method to reduce the occurrence of adverse reactions.

675-P: Effects of Liraglutide in T1D by Baseline Anthropometrics in ADJUNCT One and Two

We re-evaluated the efficacy and safety of liraglutide, a GLP-1 analog, for use as adjunctive therapy in people with type 1 diabetes (T1D). Results from the two ADJUNCT trials suggested that residual beta-cell function is associated with more pronounced benefits and less risk of hypoglycemia. Here we analyze results of the two trials according to other baseline anthropometrics. ADJUNCT ONE (NCT01836523) and TWO (NCT02098395) were randomized controlled phase 3 trials in broad T1D populations (1398 and 835 participants, respectively) treated with liraglutide (1.8, 1.2 or 0.6 mg) or placebo. ADJUNCT ONE was a 52-week trial with a treat-to-target design and no limits on insulin titration; ADJUNCT TWO was a 26-week trial with an individual maximal insulin dose. In a post hoc analysis, we evaluated certain estimated placebo-adjusted treatment effects across clinically relevant participant subgroups. At week 26 in ADJUNCT ONE, placebo-adjusted reductions in HbA1c, body weight (BW) and daily insulin dose (up to -0.30 %-points, -5.0 kg and -12%, respectively, with liraglutide 1.8 mg) were significant (p&amp;lt;0.05) and greater than at week 52. In both trials, the placebo-adjusted reductions in HbA1c, BW and daily insulin dose with liraglutide did not depend (p&amp;gt;0.05) on baseline HbA1c or BMI at neither week 26 nor 52. The risk of clinically significant hypoglycemia (symptomatic episodes with blood glucose &amp;lt;3.1 mmol/L) or hyperglycemia with ketosis did not differ significantly (p&amp;gt;0.05 vs. placebo) by baseline HbA1c, BMI or insulin regimen. In ADJUNCT ONE and TWO, the efficacy and glycemic safety of liraglutide did not depend on key baseline anthropometrics. This leaves residual beta-cell function the only identified parameter impacting the treatment effect of the GLP-1 analog used as an adjunct to insulin in T1D. Together with recent progress in the understanding of T1D and of the benefits of GLP-1 receptor agonism, these findings suggest a role for GLP-1 receptor agonists in T1D, warranting further study. Disclosure T. F. Dejgaard: Advisory Panel; Self; Novo Nordisk, Consultant; Self; Boehringer Ingelheim International GmbH, Research Support; Self; AstraZeneca, Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Novo Nordisk. L. Bardtrum: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. E. Christiansen: None. F. Kreiner: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. S. Madsbad: Advisory Panel; Self; AstraZeneca; Boehringer Ingelheim; Eli Lilly; Merck Sharp &amp; Dohme; Novo Nordisk; Sanofi, Research Support; Self; Novo Nordisk, Boehringer Ingelheim, Speaker’s Bureau; Self; AstraZeneca; Boehringer Ingelheim; Merck Sharp &amp; Dohme; Novo Nordisk; Sanofi. M. G. Von herrath: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. B. Von scholten: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. C. Mathieu: Advisory Panel; Self; Novo Nordisk, Sanofi, Merck Sharp and Dohme Ltd., Eli Lilly and Company, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Medtronic, ActoBio Therapeutics, Pfizer, Insulet and Zealand Pharma, Research Support; Self; Medtronic, Novo Nordisk, Sanofi and ActoBio Therapeutics, Speaker’s Bureau; Self; Novo Nordisk, Sanofi, Eli Lilly and Company, Boehringer Ingelheim, AstraZeneca and Novartis. Funding Novo Nordisk A/S

Liraglutide after diet-induced weight loss for pain and weight control in knee osteoarthritis: a randomized controlled trial

Weight loss is critical for preventing and managing obesity-related diseases. There is a notable lack of valid and reliable means to manage patients with overweight/obesity and knee osteoarthritis (KOA). To determine the efficacy and safety of liraglutide in a 30 mg/d dosing in patients with overweight/obesity and KOA. The trial was designed as a randomized controlled trial including patients between the age of 18 and 74 y with KOA and a BMI ≥27 (measured in kg/m2).Patients underwent a pre-random assignment diet intervention (week -8 to 0). At week 0, patients having lost >5% of their body weight were randomly assigned to liraglutide 3 mg/d or placebo for 52 wk. The coprimary outcomes were changes in body weight and the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale from week 0 to 52. In total, 168 patients enrolled and 156 were randomly assigned to receive liraglutide or placebo. Patients experienced a significant reduction in body weight and KOOS pain during the pre-random assignment dietary intervention period (week -8 to 0). From week 0 to 52 there was a significant difference in body weight between the liraglutide and placebo group (mean changes: -2.8 and +1.2 kg, respectively; group difference, 3.9 kg; 95% CI: -6.9, -1.0; P=0.008). There was, however, no group difference in KOOS pain (mean changes: 0.4 and -0.6 points, respectively; group difference, 0.9 points; 95% CI: -3.9, 5.7; P=0.71). Treatment-emergent adverse events related to the gastrointestinal system were experienced by 50.2% and 39.2% of patients in the liraglutide and placebo groups, respectively. In patients with KOA and overweight/obesity liraglutide added after an 8-wk pre-random assignment diet induced a significant weight loss at >52 wk but did not reduce knee pain compared to placebo. This trial was registered at clinicaltrials.gov as NCT02905864.