Safety Of Semaglutide Research Articles

EFICÁCIA E SEGURANÇA DA SEMAGLUTIDA NO TRATAMENTO DA OBESIDADE

Obesity is a chronic disease that affects millions of people worldwide. It is a multifactorial condition involving genetic, social, environmental, and behavioral factors. The treatment of obesity is complex and may involve lifestyle changes, medication, and surgery. In this sense, the general objective of this work is to investigate the efficacy and safety of semaglutide in the treatment of obesity in patients who are not diabetic. The methodology used will be an integrative literature review, which consists of the identification, synthesis, and critical analysis of published studies on the subject. The research will be carried out in books and scientific articles available on digital platforms. The results of this study may contribute to a better understanding of obesity, as well as correlating the effects of semaglutide, its efficacy, and safety in the treatment of obesity.

SEMAGLUTIDE: Weight loss, glycaemic control and safety profile in obese patients with and without type-II diabetes-An experience from Karachi, Pakistan

ABSTRACT Objective: To assess the efficacy and safety of Semaglutide (a GLP-1 receptor agonist) in obese patients with and without Type-II Diabetes Mellitus. Methods: This observational analytic cohort study was conducted in a private medical institute in Karachi Pakistan; from August 2022 to January 2023. A total of 65 obese individuals >18 years of age, with or without T2D were included. Semaglutide was started with an initial dose of 0.25 mg with an increase in dose to 0.5 mg, 1 mg and 2 mg with gap of 4 weeks between each dose escalation. Patients were kept on the maximally tolerated dose, not exceeding 2 mg/week. Patients were evaluated on the first and second follow-up at 3 and 6 months respectively, for the same parameters as noted at the initial visit, along with documentation of any adverse effect. Results: Out of 65 patients, 49.2% were female and 50.8% were male. Mean age was 49.16 ± 14.20 years. 47.7% of the patients had hypertension, 46.2% had diabetes mellitus, 35.4% had dyslipidemia and 13.8% had ischemic heart disease. All patients were using 0.5 mg of semaglutide after three months, however by six months 33.8% were using 1 mg, and 24.6% were on 2 mg, whereas 40% decided to adhere to 0.5 mg and only 1.5% decided to reduce the dose to 0.25 mg due to adverse effects. Patients reported start of the first adverse effect by 3.44 ± 2.27 weeks of starting the drug. By the end of three months, 55.4% of patients in our study reported adverse effect, which declined to 34.5% by the end of six months, and the majority being mild to moderate and the most frequent side effects were gastrointestinal in origin. There was no significant difference in side effect profile in between those with and without diabetes mellitus. The average weight loss was 5.81 ± 2.64 kg and 9.86 ± 3.54 kg after three and six months respectively and the amount of weight loss was almost equal in those with and without T2D. A significant decline was observed in the average HbA1c levels, body mass index (p = <0.001), systolic blood pressure (p = <0.001), diastolic blood pressure (p = <0.001), total cholesterol (p = <0.001), high-density lipoprotein (p = <0.001), low-density lipoprotein (p = <0.001), triglycerides (p = <0.001) and alanine transaminase levels (p = <0.001). Conclusion: Semaglutide showed substantial weight, HbA1c and cholesterol reductions in those with or without type-II diabetes.

Semaglutide: A revolution in the treatment of obesity and prevention of cardiovascular disease

Introduction and Objective: Obesity represents a significant public health concern in the 21st century, with a substantial burden of disease attributable to its complications, including type 2 diabetes, hypertension, and cardiovascular disease. The objective of this review is to evaluate the efficacy and safety of semaglutide, a GLP-1 receptor agonist, in the treatment of obesity and its impact on cardiometabolic risk factors. The Review and Methods: This review is based on an analysis of the scientific literature, including meta-analyses and clinical trials. The PubMed, Scopus and Web of Science databases were searched for publications up to 2023. Abridged Description of the State of Knowledge: The efficacy of semaglutide in reducing body weight in patients with obesity is supported by evidence from clinical trials. Its mechanism of action includes the delay of gastric emptying and the reduction of hunger. The drug has been demonstrated to exert a beneficial effect on the lipid profile and blood pressure, thereby reducing the risk of cardiovascular disease. The adverse effects, which are primarily gastrointestinal in nature, are typically mild and resolve with treatment. Summary: Semaglutide represents a promising therapeutic option for obese patients, offering an effective means of reducing body weight and improving cardiometabolic parameters. However, further studies are required to evaluate the long-term effects of this therapy and its application in different patient populations. Keywords: Semaglutide, obesity, weight reduction, GLP-1, cardiometabolic risk factors, drug treatment.

Effectiveness and safety of semaglutide in overweight/obese adults with or without type 2 diabetes: A systematic review and meta-analysis

Background: The objective of the study was to systematically evaluate the efficacy and safety of semaglutide in overweight or obese adults with or without type 2 diabetes. Materials and Methods: The study, registered with PROSPERO (CRD42023450979), was designed as a systematic review and meta-analysis. Using a combination of subject matter and free words, a comprehensive search of Embase, PubMed, and Cochrane Library databases was performed to identify randomized controlled trials of semaglutide in overweight or obese adults with or without Type 2 diabetes mellitus from January 1, 2020, to July 14, 2023. The primary outcomes were the changes in body weight and adverse drug reaction (ADR). Random or fixed effects models were used in meta-analysis, pooling data as relative risks (RRs) or mean difference (MD) with 95% confidence intervals (CIs). Cochrane Collaboration’s Risk of Bias tool was used to assess quality. Meta-analysis was performed using RevMan 5.3. Results: A total of 2490 publications were retrieved. Fifteen publications were finally included, totaling 6984 overweight or obese adult patients. Meta-analysis showed that compared with the control group, the semaglutide group was reduced more significantly in body weight (MD = −7.49, 95% CI [−9.92, −5.07], P < 0.001), body mass index (MD = −3.35, 95% CI [−4.79, −1.92], P < 0.001), waist circumference (MD = −7.26, 95% CI [−9.94, −4.58], P < 0.001), as well as glycosylated hemoglobin (RR = −0.66, 95% CI [−1.07, −0.25], P = 0.002), fasting blood glucose values (RR = −4.81, 95% CI [−7.03, −2.60], P < 0.001), and systolic blood pressure (RR = −3.37, 95% CI [−5.32, −1.42], P < 0.001), and the proportion of patients who lost > 5%, 10%, 15%, and 20% of their overall body weight, respectively (RR = 3.19, 95% CI [1.89, 5.36], P < 0.001), (RR = 4.74, 95% CI [2.78, 8.11], P < 0.001), (RR = 6.17, 95% CI [3.88, 9.82], P < 0.001), and (RR = 9.14, 95% CI [6.05, 13.80], P < 0.001) were also superior to the control group. Regarding safety, the incidence of total ADR in the semaglutide group was close to the placebo group. Still, gastrointestinal adverse effects such as nausea, vomiting, abdominal pain, and diarrhea were higher than those in the control group. Conclusion: Semaglutide can effectively lose weight in overweight or obese adults with or without diabetes, potentially providing cardiovascular benefits; however, gastrointestinal adverse should be closely monitored.

Effect of Semaglutide in Individuals With Obesity or Overweight Without Diabetes.

This systematic review evaluates the efficacy and safety of semaglutide in individuals with obesity or overweight without diabetes. Obesity is a significant public health concern, associated with various comorbidities and reduced quality of life. Semaglutide, a glucagon-like peptide-1 receptor agonist, has emerged as a promising pharmacological intervention for weight management. This review synthesizes findings from multiple clinical trials, highlighting the impact of semaglutide on weight loss, metabolic parameters, and overall health outcomes in non-diabetic populations. The review also addresses methodological considerations, including study design, participant selection, and outcome measures, to assess the robustness of the evidence. Ethical considerations and potential conflicts of interest are discussed to ensure transparency in the research process. The findings indicate that semaglutide is associated with significant weight reduction and improvement in obesity-related health markers, suggesting its potential as a valuable treatment option for individuals struggling with obesity. Limitations of the current literature and recommendations for future research directions are also presented, emphasizing the need for further studies to explore the long-term effects and generalizability of semaglutide treatment in diverse populations.

Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. Novo Nordisk.

Efficacy and safety of once-weekly semaglutide 2·4 mg versus placebo in people with obesity and prediabetes (STEP 10): a randomised, double-blind, placebo-controlled, multicentre phase 3 trial

There are currently limited data regarding the effect of semaglutide 2·4 mg in individuals with obesity and prediabetes in clinical trials. We aimed to assess the efficacy and safety of semaglutide 2·4 mg for weight management and glycaemic control in participants with obesity and prediabetes. STEP 10 was a randomised, double-blind, parallel-group, phase 3 trial done across 30 trial sites in Canada, Denmark, Finland, Spain, and the UK and included participants aged 18 years or older with a BMI of 30 kg/m2 or higher and prediabetes according to UK National Institute for Health and Care Excellence criteria (defined as having at least one of the following at screening: HbA1c of 6·0-6·4% [42-47 mmol/mol] or fasting plasma glucose [FPG] of 5·5-6·9 mmol/L). Participants were randomly assigned (2:1) to once-weekly subcutaneous semaglutide 2·4 mg or placebo with diet and physical activity counselling for 52 weeks, followed by a 28-week off-treatment period. Primary endpoints were percentage change in bodyweight and proportion of participants reverting to normoglycaemia (HbA1c <6·0% [<42 mmol/mol] and FPG <5·5 mmol/L) at week 52 (assessed in all randomly assigned participants by intention to treat). Selective safety data were collected for participants who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT05040971, and is complete. Between Sept 16 and Dec 29, 2021, 138 participants were randomly assigned to semaglutide 2·4 mg and 69 to placebo. 147 (71%) were female and 60 (29%) were male; 183 (88%) were White. All randomly assigned participants received at least one dose of study drug. Baseline mean age was 53 years (SD 11), bodyweight 111·6 kg (22·2), BMI 40·1 kg/m2 (6·9), waist circumference 120·1 cm (14·7), HbA1c 5·9% (0·3; 41·3 mmol/mol [3·0]), and FPG 5·9 mmol/L (0·6). There was a significantly greater reduction in bodyweight with semaglutide 2·4 mg than with placebo at week 52 (-13·9% [SD 0·7] vs -2·7% [0·6]; estimated treatment difference -11·2% [95% CI -13·0 to -9·4]; p<0·0001). Greater proportions of participants reverted to normoglycaemia at week 52 with semaglutide 2·4 mg than with placebo (103 [81%] of 127 vs nine [14%] of 64; odds ratio 19·8 [95% CI 8·7 to 45·2]; p<0·0001). Serious adverse events occurred in 12 (9%) participants receiving semaglutide 2·4 mg versus six (9%) receiving placebo. Adverse events leading to treatment discontinuation occurred in eight (6%) participants in the semaglutide 2·4 mg group versus one (1%) participant in the placebo group. No new safety signals were reported. Semaglutide 2·4 mg provided superior reduction in bodyweight and reversion to normoglycaemia versus placebo in participants with obesity and prediabetes. The safety and tolerability profile was consistent with previous studies and with the GLP-1 receptor agonist class. These findings support the potential use of semaglutide 2·4 mg as a treatment option for individuals with obesity and prediabetes to achieve reversion to normoglycaemia. Novo Nordisk. For the Spanish translation of the abstract see Supplementary Materials section.

Efficacy and safety of semaglutide 2.4 mg by race and ethnicity: A post hoc analysis of three randomized controlled trials.

The objective of this study was to evaluate the efficacy and safety of semaglutide 2.4 mg, a glucagon-like peptide-1 receptor agonist, by race and ethnicity, across three phase 3 trials. The Semaglutide Treatment Effect in People with Obesity (STEP) clinical trials evaluated the efficacy and safety of once-weekly subcutaneous semaglutide 2.4 mg. Here, STEP 1 and 3 data were pooled for analysis; STEP 2 data were examined separately. All analyses were conducted using data from racial and ethnic subgroups. The primary outcome was the estimated treatment difference in percent body weight change for semaglutide 2.4 mg versus placebo. Participants reported race as White (STEP 1 and 3, 75.3%; STEP 2, 59.4%), Black (8.8%; 8.9%), Asian (10.6%; 27.3%), or other racial group (5.3%; 4.4%); and ethnicity as Hispanic or Latino (13.9%; 11.9%) or not Hispanic or Latino (83.9%; 88.1%). There were no significant interactions between treatment effect and race (STEP 1 and 3: p ≥ 0.07; STEP 2: p ≥ 0.15) or ethnicity (p ≥ 0.40; p ≥ 0.85). The safety of semaglutide 2.4 mg was consistent across subgroups. The treatment effect of semaglutide was statistically significant versus placebo and clinically relevant across all racial and ethnic subgroups in STEP 1 and 3 and STEP 2. All subgroups across both samples demonstrated good tolerability.

Efficacy and Safety of Semaglutide in Weight Loss of Non-diabetic People.

The study aimed to investigate the efficacy and safety of semaglutide in weight loss in non-diabetic people. In this study, 84 non-diabetic people who used semaglutide to lose weight in the outpatient department of our hospital from January 1, 2022, to June 30, 2022, were enrolled and compared for changes in body weight, waist circumference, Body Mass Index (BMI), fasting blood glucose, blood pressure, pulse, and body composition (body fat ratio, visceral fat area, and skeletal muscle) before treatment and 12 weeks after the treatment to analyze the weight loss efficacy and safety. After administering semaglutide 0.25 mg, 0.5 mg, 0.75 mg, or 1 mg subcutaneously once a week for 12 weeks, 84 participants in this study obtained an average weight loss of 5.91 ± 3.37 kg, equivalent to 6.15 ± 4.28% of baseline body weight, and there was also a significant reduction in visceral fat area and a slight reduction in blood pressure. The most common adverse reactions included gastrointestinal reactions (nausea, vomiting, and diarrhea), which were mild and subsided within 1-2 days. No severe adverse reaction, such as hypoglycemia and hypotension, was observed. Low-dose semaglutide has been found to be effective and safe for short-term weight loss in non-diabetic people.

Semaglutide combined with empagliflozin vs. monotherapy for non-alcoholic fatty liver disease in type 2 diabetes: Study protocol for a randomized clinical trial.

Nonalcoholic fatty liver disease (NAFLD) is strongly associated with type 2 diabetes mellitus (T2DM). Lifestyle intervention remains a preferred treatment modality for NAFLD. The glucagon-like peptide (GLP-1) receptor agonists and sodium-glucose cotransporter-2 (SGLT-2) inhibitors have been developed as new glucose-lowering drugs, which can improve fatty liver via an insulin-independent glucose-lowering effect. However, studies exploring the efficacy of GLP-1 receptor agonists combined with SGLT-2 inhibitors in patients with NAFLD and T2DM are scanty. Thus, the present randomised controlled trial aims at comparing the efficacy and safety of semaglutide plus empagliflozin with each treatment alone in patients with NAFLD and T2DM. This 52-week double-blinded, randomised, parallel-group, active-controlled trial evaluates the effects of semaglutide, empagliflozin and semaglutide + empagliflozin in 105 eligible overweight/obese subjects with NAFLD and T2DM. The primary outcome will be a change from baseline to week 52 in the controlled attenuation parameter, free fatty acid and glucagon. Secondary endpoints include changes in liver stiffness measurement, liver enzymes, blood glucose, lipid levels, renal function, electrolyte balances, minerals and bone metabolism, cytokines, high-sensitivity C-reactive protein, ferritin, anthropometric indicators, nonalcoholic fatty liver fibrosis score, fibrosis 4 score and homeostatic model assessment for insulin resistance. In addition, intention-to-treat, interim analysis and safety analysis will be performed. This double-blinded, randomised, clinical trial involves a multi-disciplinary approach and aims to explore the synergistic effects of the combination of semaglutide and empagliflozin. The results can provide important insights into mechanisms of GLP-1 receptor agonists and/or SGLT-2 inhibitors in patients with NAFLD and T2DM. This study has been registered with Chinese Clinical Trial Registry (ChiCTR2300070674).

Effect of semaglutide 2.4 mg on physical functioning and weight- and health-related quality of life in adults with overweight or obesity: Patient-reported outcomes from the STEP 1-4 trials.

To summarize the effects of semaglutide 2.4 mg on weight-related quality of life (WRQOL) and health-related quality of life (HRQOL), focusing on the confirmatory secondary endpoint of physical functioning. The STEP 1-4 Phase 3a, 68-week, double-blind, randomized controlled trials assessed the efficacy and safety of semaglutide 2.4 mg versus placebo in individuals with overweight/obesity. WRQOL and HRQOL were assessed by change from baseline to Week 68 in two different but complementary measures, the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT; STEP 1 and 2) and the SF-36v2 Health Survey Acute (SF-36v2; STEP 1-4). Superiority for semaglutide 2.4 mg over placebo based on IWQOL-Lite-CT and SF-36v2 physical functioning scores was confirmed in STEP 1 and 2 and in STEP 1, 2 and 4, respectively. At Week 68, a greater proportion of participants treated with semaglutide 2.4 mg than with placebo reached meaningful within-person change (MWPC) thresholds for IWQOL-Lite-CT Physical Function scores in STEP 1 (51.8% vs. 28.3%; p < 0.0001) and STEP 2 (39.6% vs. 29.5%; p = 0.0083) and the MWPC threshold for SF-36v2 Physical Functioning in STEP 1 (39.8% vs. 24.1%; p < 0.0001), STEP 2 (41.0% vs. 27.3%; p = 0.0001) and STEP 4 (18.0% vs. 6.6%; p < 0.0001). All other IWQOL-Lite-CT and SF-36v2 scale scores in STEP 1-4 were numerically improved with semaglutide 2.4 mg versus placebo, except for SF-36v2 Role Emotional in STEP 2. Semaglutide 2.4 mg significantly improved physical functioning, with greater proportions of participants achieving MWPC compared with placebo, and showed beneficial effects on WRQOL and HRQOL beyond physical functioning.

Efficacy and safety of semaglutide in patients with heart failure with preserved ejection fraction and obesity.

Semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, has shown promise in weight management and cardiovascular outcomes in other populations. This study aimed to evaluate the efficacy of semaglutide in heart failure with preserved ejection fraction(HFpEF) patients with obesity. A retrospective study analyzed 318 patients with HFpEF, of which 104 received semaglutide and 214 received placebo. Primary endpoints included evaluating changes in exercise capacity and weight management. Semaglutide treatment led to significant improvements in the primary endpoints. Patients in the semaglutide group demonstrated substantial enhancements in exercise capacity, as measured by the 6-min walk distance, compared to the placebo group (mean difference 15.1 meters, 95% CI 5.8 to 24.4, p = 0.002). Additionally, semaglutide resulted in substantial weight loss compared to placebo (mean difference -2.9%, 95% CI -4.1--1.7, p = 0.001). Several secondary endpoints, including reductions in C-reactive protein levels and improvements in other clinical parameters, further supported the efficacy of semaglutide. Adverse events were generally well-tolerated, with no unexpected safety concerns. Semaglutide demonstrated significant clinical benefits in HFpEF patients with obesity, as evidenced by improved symptoms, physical function, and weight reduction.

Long-Term Efficacy and Safety of Once-Weekly Semaglutide for Weight Loss in Patients Without Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated clinically important weight loss effects in patients with type 2 diabetes. However, its effects on sustained weight loss in patients without diabetes remains unclear. Our objective was to examine the long-term efficacy and safety of semaglutide use for weight loss in patients with overweight/obesity and without diabetes. MEDLINE, EMBASE, and the Cochrane Libraries were systematically searched to identify randomized controlled trials that randomized participants with overweight/obesity and without diabetes to once-weekly 2.4 mg subcutaneous semaglutide versus placebo, with a follow-up of at least 68 weeks. The primary outcome was a change in relative body weight from baseline to the longest follow-up. Random-effects models with inverse variance weighting were used to estimate the weighted mean differences (WMDs) and relative risks (RRs) with 95% confidence intervals (CIs). A total of 4 randomized controlled trials (n = 3,087) were included. Of the 3 trials that provided body mass index by category (n = 2,783), 94.0% of the participants had a baseline body mass index ≥30 kg/m2. Compared with placebo, the use of semaglutide was associated with substantial decreases in long-term relative (WMD -12.1%, 95% CI -13.5 to -10.7) and absolute body weight (WMD -12.3 kg, 95% CI -13.6 to -11.0). At the longest follow-up, 33.4% of participants randomized to semaglutide achieved ≥20% weight loss compared with 2.2% with placebo (RR 15.08, 95% CI 9.31 to 24.43). The risk of gastrointestinal adverse events was higher in participants who took semaglutide than placebo (RR 1:47, 95% CI 1.28 to 1.68); however, the majority of these events were transient and mild-to-moderate in severity and did not require treatment discontinuation. In conclusion, semaglutide is efficacious for sustained weight loss in patients with overweight/obesity and without diabetes.

Assessment of Thyroid Carcinogenic Risk and Safety Profile of GLP1-RA Semaglutide (Ozempic) Therapy for Diabetes Mellitus and Obesity: A Systematic Literature Review.

The broadening application of glucagon-like peptide (GLP)-1 receptor agonists, specifically semaglutide (Ozempic) for the management of diabetes and obesity brings a critical need to evaluate its safety profile, considering estimates of up to 20 million prescriptions per year in the US until 2035. This systematic review aims to assess the incidence of thyroid cancer and detail the spectrum of adverse events associated with semaglutide, focusing on its implications for patient care. Through a systematic search of PubMed, Scopus, and Embase databases up to December 2023, ten randomized controlled trials (RCTs) involving 14,550 participants, with 7830 receiving semaglutide, were analyzed, with an additional number of 18 studies that were separately discussed because they reported data from the same RCTs. The review focused on thyroid cancer incidence, gastrointestinal symptoms, and other significant adverse events attributed to semaglutide. The incidence of thyroid cancer in semaglutide-treated patients was less than 1%, suggesting no significant risk. Adverse events were predominantly gastrointestinal, including nausea (2.05% to 19.95%) and diarrhea (1.4% to 13%). Nasopharyngitis and vomiting were also notable, with mean prevalences of 8.23% and 5.97%, respectively. Other adverse events included increased lipase levels (mean of 6.5%), headaches (mean prevalence of 7.92%), decreased appetite (reported consistently at 7%), influenza symptoms (mean prevalence of 5.23%), dyspepsia (mean prevalence of 5.18%), and constipation (mean prevalence of 6.91%). Serious adverse events varied from 7% to 25.2%, highlighting the need for vigilant patient monitoring. These findings underscore the gastrointestinal nature of semaglutide's adverse events, which, while prevalent, did not significantly deter from its clinical benefits in the treatment landscape. This systematic review provides a comprehensive assessment of semaglutide's safety profile, with a focus on gastrointestinal adverse events and a low incidence of thyroid cancer. Despite the prevalence of gastrointestinal symptoms, semaglutide remains an efficacious option for managing diabetes and obesity. The detailed characterization of adverse events underscores the importance of monitoring and managing these effects in clinical practice, excluding the hypothesis of carcinogenesis.

Safety and Efficacy of Semaglutide Use in Diabetes during Ramadan Fasting: A Real-world Experience from Bangladesh

Aims: The study has been conducted to observe the efficacy and safety of once-weekly subcutaneous semaglutide during Ramadan fasting among patients with type 2 diabetes mellitus (T2DM) from Bangladesh who intended to fast during Ramadan 2022. Methods: This was an open-label, single-center, two-arm parallel-group study. In this prospective observational study, patients were enrolled in two groups depending on treated with or without semaglutide for at least 3 months prior Ramadan. Initially, total 200 patients were enrolled at the first visit (4 weeks before Ramadan); among them, 58 subjects were in the semaglutide group (Group A) and 142 in other than the semaglutide group (Group B). At the end of the second visit (within 4 weeks after Ramadan) after data editing and cleaning, a total of 130 patients (55 subjects in Group A and 75 subjects in Group B) were included in the final statistical analysis. All of them were followed up for a total of 24 weeks including 12 weeks of screening period. The primary objectives were to assess the efficacy and safety of semaglutide in terms of glycosylated hemoglobin (HbA1c) (%), weight loss (kg), hypoglycemia (number of events), and episodes of gastrointestinal (GI) upset (number of events) during Ramadan fasting. Results: Patients in the semaglutide group had better glycemic control after fasting of Ramadan compared to the control group (mean decrease in HbA1c level: 0.61% vs. 0.19%; P &lt; 0.001). In addition, more than 18% of the patients in the semaglutide group achieved good glycemic control (HbA1c &lt;7%), while the rate was 13.3% in the control group. Patients treated with semaglutide achieved a better weight loss than the nonsemaglutide group (2.97 vs. 1.38 kg; P &lt; 0.001). Although there was no significant difference in terms of hypoglycemic events in both the groups (P = 0.13), but the GI symptoms were more common in the semaglutide group than the control group (P &lt; 0.05). Among other secondary endpoints, the serum levels of total cholesterol, low-density lipoprotein, and triglyceride were significantly decreased in the semaglutide group compared to the control group (P &lt; 0.05). Conclusions: Semaglutide showed better efficacy in glycemic control, weight loss, and dyslipidemia compared to other hypoglycemic drugs in patients with T2DM during Ramadan. Although patients receiving semaglutide reported fewer hypoglycemic episodes and GI upset events, they might be subjected to other medications or prolonged fasting. Semaglutide might be considered a suitable therapy during Ramadan fasting based on judicial judgment.

Semaglutide in type 2 diabetes management: review of current evidence from concept to date

Clinical guidelines increasingly emphasize the importance of multifactorial treatment of type 2 diabetes (DM2), including both glycemic control and body weight control, comprehensive management of classical cardiological risk factors, as well as the use of drugs with proven cardionephroprotective effects to reduce the risk of long-term complications. The development of semaglutide, a long—acting and highly homologous receptor agonist of glucagon-like peptide-1 (arGPP-1) based on a widely recognized representative of the liraglutide class, was an important milestone in expanding the possibilities of disease management, and the successes achieved in the clinical research program of the drug contributed to the formation of the above aspects of the recommendations.The clinical efficacy of semaglutide was evaluated in the framework of the SUSTAIN clinical research program for more than 10,000 patients with DM2. The program includes 6 major global studies of Phase IIIa (SUSTAIN 1-6) and 5 studies of phase IIIb (SUSTAIN 7-11), as well as a number of other studies and analyses.The development of a domestic reproduced drug containing semaglutide will increase the availability of semaglutide preparations in the Russian Federation, as well as significantly more effectively control the level of glycemia in patients with DM2. This review presents the results of the efficacy and safety of semaglutide, including the Russian bioequivalent drug semaglutide.

Evaluating the Clinical Effectiveness and Safety of Semaglutide in Individuals with Uncontrolled Type2 Diabetes. Real-World Evidence from Saudi Arabia: The Observational, Multicenter, 15-Month EVOLUTION Study.

This study aimed to assess the safety and effectiveness of semaglutide, administered either by weekly subcutaneous (SC) injection or orally, in real-life practice in Saudi Arabia in individuals with type2 diabetes mellitus (T2DM). A retrospective chart review study was conducted at 18 Saudi Arabia centers. An accredited centralized institutional review board approved the study. Medical records were included for individuals of any age ≥ 18years with uncontrolled T2DM. The primary outcome measure was the laboratory glycated hemoglobin (HbA1c) level.Secondary measures included fasting blood glucose (FBG), weight, and hypoglycemia. All variables were checked after 6 and 12months of semaglutide initiation. The analysis of this study included 1223 patients with uncontrolled T2DM (HbA1c > 7%). The mean (SD) baseline HbA1c was 10.02% (1.17). HbA1c was reduced by an average of 3.02% (0.84) and 3.17% (0.84) at 6 and 12months, respectively. Results of a repeated measure analysis of variance (ANOVA) indicated significant differences in HbA1c (pvalue < 0.001). HbA1c levels at 6 and 12months were significantly lower, 7.00% (0.70) and 6.85% (0.69), than at baseline, 10.02% (1.17). About 193 patients (56.4%) of the 295 patients having HbA1c < 9% achieved HbA1c of 5.7% or less. The frequency of hypoglycemia events was 4.60 (1.10) in the 3months before semaglutide was initiated. The frequency of hypoglycemia events in the last 3months was 2.30 (0.80) events and 0.80 (0.50) events at 6-month and 12-month follow-up visits, respectively. The percent reduction in body mass index (BMI) was an average of 13.07% (1.53) and 19.89% (4.07) at 6 and 12months, respectively. Lipid profile and blood pressure were improved at 6 and 12months. Semaglutide, administered either by SC injection or orally, provided substantial glycemic and weight-loss benefits in adults with T2DM.

Efficacy and safety of semaglutide 2.4 mg for weight loss in overweight or obese adults without diabetes: An updated systematic review and meta-analysis including the 2-year STEP 5 trial.

To explore the safety and efficacy of subcutaneous semaglutide 2.4 mg, administered once a week in non-diabetic overweight or obese individuals. A thorough search was performed of various databases including PubMed, Embase, the Cochrane Library, Web of Science, clinicaltrials.gov, CNKI and Wanfang from their inception up to April 11, 2023. Our aim was to identify randomized controlled trials (RCTs) that compared the efficacy of semaglutide administered once weekly with placebo in overweight or obese adults. Through a review of the literature, data were extracted from relevant studies and assessed for quality, and a meta-analysis was conducted using RevMan 5.4.1 software. Six RCTs comprising 3962 overweight or obese individuals were identified. The findings indicated that, in comparison to the placebo group, semaglutide caused a significant and sustainable reduction in the percentage of body weight (BW; mean difference [MD]: -11.80% [95% confidence interval {CI} -12.93, -10.68]; P < 0.00001) as well as a decrease in absolute BW (MD: -12.2 kg [95% CI -13.3, -11.1]; P < 0.00001), body mass index (MD: -4.5 kg/m2 [95% CI -4.9, -4.1]; P < 0.00001) and waist circumference (MD:-9.4 cm [95% CI -10.1, -8.8]; P < 0.00001). Moreover, it achieved a higher proportion of patients who experienced weight loss exceeding 5%, 10%, 15% and 20%. Furthermore, semaglutide showed significant efficacy in controlling blood pressure, blood sugar levels, C-reactive protein levels, and lipid profiles. In terms of safety, the most common adverse effects following semaglutide treatment were gastrointestinal adverse reactions (risk ratio: 1.49 [95% CI 1.38, 1.60]; P < 0.00001), which were generally mild to moderate in severity and temporary. In overweight or obese non-diabetic individuals, semaglutide had a remarkable and sustained weight loss effect that was well tolerated and safe.

Efficacy and safety of semaglutide 2.4 mg according to antidepressant use at baseline: A post hoc subgroup analysis.

To explore the efficacy and safety of semaglutide 2.4 mg in people with overweight/obesity who were also being treated with antidepressants (ADs). Across the Semaglutide Treatment Effect for People with obesity (STEP) 1-3 and 5 trials, adults with overweight/obesity and type 2 diabetes (STEP 2 only) were enrolled. People with severe major depressive disorder within 2 years prior to screening or with a patient health questionnaire-9 score ≥15 at screening were excluded. Participants were categorized into subgroups according to baseline AD status (on/off ADs) in this post hoc exploratory analysis of the STEP trials. Of 3683 participants randomized, 539 were on ADs at baseline. Mean body weight change from baseline to week 68 was greater for semaglutide versus placebo, regardless of baseline AD use. In STEP 1, for participants on ADs at baseline, mean change from baseline was -15.7% with semaglutide versus -0.2% with placebo and -14.7% versus -2.8% for those not on ADs at baseline. Similar patterns were seen in STEP 2, 3, and 5. The prevalence of adverse events (AEs) was generally similar between semaglutide and placebo in participants on ADs at baseline. In adults with overweight/obesity, semaglutide provided clinically meaningful weight loss regardless of baseline AD use, with an AE profile consistent with previous studies.

Efficacy and safety of semaglutide in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. The prevalence and disease burden of NAFLD are projected to exponentially increase resulting in significant healthcare expenditures and lower health-related quality of life. To date, there are no approved pharmacotherapies for NAFLD or non-alcoholic steatohepatitis (NASH). Semaglutide has glycemic and weight loss benefits that may be advantageous for patients with NAFLD. To investigate the efficacy and safety of semaglutide in patients with NAFLD. MEDLINE, CENTRAL, and EMBASE were searched from inception to May 1, 2023, to identify eligible randomized controlled trials (RCTs). Meta-analysis was performed using random effects model expressing continuous outcomes as mean differences (MD) or standardized MDs (SMD), and dichotomous outcomes as odds ratios (OR) with 95% confidence intervals (CI). Statistical heterogeneity was assessed using the Cochran's Q test and I2 statistic. Three RCTs involving 458 patients were included. Semaglutide increased the likelihood of NASH resolution (OR: 3.18, 95%CI: 1.70, 5.95; P < 0.001), improvement in steatosis (OR: 2.83, 95%CI: 1.19, 6.71; P = 0.03), lobular inflammation (OR: 1.81, 95%CI: 1.11, 2.96; P = 0.02), and hepatocellular ballooning (OR: 2.92, 95%CI: 1.83, 4.65; P < 0.001), but not fibrosis stage (OR: 0.71, 95%CI: 0.15, 3.41; P = 0.67). Radiologically, semaglutide reduced liver stiffness (SMD: -0.48, 95%CI: -0.86, -0.11; P = 0.01) and steatosis (MD: -4.96%, 95%CI: -9.92, 0.01; P = 0.05). It also reduced alanine aminotransferase (MD: -14.06 U/L, 95%CI: -22.06, -6.07; P < 0.001) and aspartate aminotransferase (MD: -11.44 U/L, 95%CI: -17.23, -5.65; P < 0.001). Semaglutide led to improved cardiometabolic outcomes, including decreased HgA1c (MD: -0.77%, 95%CI: -1.18, -0.37; P < 0.001) and weight loss (MD: -6.53 kg, 95%CI: -11.21, -1.85; P = 0.006), but increased the occurrence of GI-related side effects (OR: 3.72, 95%CI: 1.68, 8.23; P = 0.001). Overall risk of serious adverse events was similar compared to placebo (OR: 1.40, 95%CI: 0.75, 2.62; P < 0.29). Semaglutide is effective in the treatment of NAFLD while maintaining a well-tolerated safety profile. Future studies are required to evaluate its effects on fibrosis regression and different phases of NAFLD.