Explore studies of semaglutide.
New diabetes drugs include GLP-1 agonists (exenatide, liraglutide: injectable, weight loss, low hypo risk), DPP-4 inhibitors (sitagliptin, vildagliptin: oral, weight neutral), and amylin analog (pramlintide) — peptide-based drugs transforming type 2 diabetes treatment.
Krentz, Andrew J; Patel, Mayank B; Bailey, Clifford J · Review
Once-weekly semaglutide (0.5 mg and 1.0 mg) offered superior cost-per-outcome versus exenatide extended-release and dulaglutide for type 2 diabetes. Semaglutide was the most effective at getting patients to all three treatment targets: HbA1c below 7.0%, HbA1c below 7.0% without hypoglycemia or weight gain, and a combined target of ≥1.0% HbA1c reduction with ≥5.0% weight loss. Critically, the cost-to-efficacy ratio also favored semaglutide — meaning it wasn't just more effective, but more cost-effective per patient who reached treatment goals. This held true for both the simple glycemic target and the more demanding composite endpoints.
Johansen, Pierre; Hunt, Barnaby; Iyer, Neeraj N; Dang-Tan, Tam; Pollock, Richard F · Health Economics / Cost Effectiveness Analysis
At 26 weeks, oral semaglutide 14 mg reduced HbA1c by 1.0 percentage point versus 0.2 for placebo (treatment difference: -0.8 percentage points; p<0.0001). Body weight decreased by 3.7 kg with semaglutide versus 1.1 kg with placebo (treatment difference: -2.7 kg; p<0.0001). In the on-treatment analysis (excluding patients who discontinued or needed rescue medication), the HbA1c reduction was even larger: -1.1 versus -0.1 percentage points. Completion rates were 82% for semaglutide and 88% for placebo. More patients discontinued semaglutide due to adverse events (15% vs 5%), primarily gastrointestinal symptoms. Renal safety was consistent with the GLP-1 receptor agonist class.
Mosenzon, Ofri; Blicher, Thalia Marie; Rosenlund, Signe; Eriksson, Jan W; Heller, Simon; Hels, Ole Holm; Pratley, Richard; Sathyapalan, Thozhukat; Desouza, Cyrus · Randomized Controlled Trial
The cost-of-control analysis compared oral semaglutide 14 mg against six injectable GLP-1 receptor agonists for type 2 diabetes. The calculation divides annual drug cost by the proportion of patients reaching HbA1c targets. For the HbA1c ≤6.5% target, costs per patient achieving control: injectable semaglutide 1 mg was cheapest at $15,430, followed by oral semaglutide 14 mg at $17,383. All others (dulaglutide, exenatide once-weekly and twice-daily, liraglutide, lixisenatide) cost more per controlled patient. For HbA1c <7.0%: injectable semaglutide 1 mg led at $12,627, followed by oral semaglutide at $13,493. The pattern was consistent. Oral semaglutide was likely cost-effective versus all comparators except injectable semaglutide. This matters because some patients strongly prefer pills over injections.
Hansen, B B; Nuhoho, S; Ali, S N; Dang-Tan, T; Valentine, W J; Malkin, S J P; Hunt, B · Cost Effectiveness Analysis
Prior cardiovascular outcome trials showed semaglutide reduced MACE (major adverse cardiovascular events: CV death, non-fatal stroke, non-fatal MI) in high-risk patients. This post hoc analysis asked: does the benefit extend to lower-risk patients? A cardiovascular risk prediction model was developed from LEADER trial data and validated on the semaglutide dataset (area under the curve: 0.77, indicating good predictive performance). Key finding: semaglutide reduced both relative and absolute risk of MACE versus comparators across the entire continuum of cardiovascular risk. The relative risk reduction tended to be largest in patients with low CV risk scores. The absolute risk reduction was largest for intermediate to high risk scores (because these patients had more events to prevent). Previous data: SUSTAIN-6 showed HR 0.74 [0.58-0.95] for injectable semaglutide vs placebo. PIONEER 6 showed HR 0.79 [0.57-1.11] for oral semaglutide vs placebo. This analysis extends those findings across the risk spectrum. Similar patterns were seen for individual MACE components and when only placebo comparator data were included.
Husain, Mansoor; Bain, Stephen C; Holst, Anders Gaarsdal; Mark, Thomas; Rasmussen, Søren; Lingvay, Ildiko · Post Hoc Analysis Of Phase 3 Clinical Trials
Combining individual patient-level data from SUSTAIN 6 (injectable semaglutide) and PIONEER 6 (oral semaglutide) versus placebo: Overall MACE: HR 0.76 (95% CI 0.62-0.92), a 24% reduction. This was statistically significant. Individual components: non-fatal stroke showed the strongest effect at HR 0.65 (95% CI 0.43-0.97), a 35% reduction. CV death and non-fatal MI showed numerical reductions but individual confidence intervals were wider. Heart failure hospitalization: HR 1.03 (95% CI 0.75-1.40), no benefit. Notably, patients with prior heart failure also showed no MACE benefit (interaction P = 0.046). Subgroup analyses: consistent MACE reduction in patients with and without established CV disease or chronic kidney disease, and in patients with and without prior MI or stroke (all interaction P > 0.05 except HF). In the combined glycemic efficacy trials (where comparators included active drugs, not just placebo), MACE HR was 0.85 (95% CI 0.55-1.33).
Husain, Mansoor; Bain, Stephen C; Jeppesen, Ole K; Lingvay, Ildiko; Sørrig, Rasmus; Treppendahl, Marianne B; Vilsbøll, Tina · Pooled Post Hoc Analysis Of Cardiovascular Outcome Trials
Annual per-patient costs were similar across all four GLP-1 receptor agonists in the UK market. However, once-weekly semaglutide consistently outperformed the others in getting patients to treatment goals. For the composite endpoint of HbA1c below 7.0% without weight gain or low blood sugar episodes, the competing drugs fell short: exenatide ER was 50.0% less effective, liraglutide was 51.3% less effective, and dulaglutide was 21.6% less effective than semaglutide. Semaglutide also led in single endpoints including HbA1c targets (below 7.0% and below 7.5%) and meaningful weight loss (5% or more body weight reduction).
Johansen, Pierre; Sandberg, Anna; Capehorn, Matthew · Cost Effectiveness Analysis
No statistical heterogeneity in cardiovascular (MACE) or nephropathy outcomes across blood pressure categories for either liraglutide or semaglutide vs placebo.
Leiter, Lawrence A; Bain, Stephen C; Bhatt, Deepak L; Buse, John B; Mazer, C David; Pratley, Richard E; Rasmussen, Søren; Ripa, Maria Sejersten; Vrazic, Hrvoje; Verma, Subodh · Post Hoc Analysis Of RCTs
GLP-1 receptor agonists reduce macro-albuminuria in cardiovascular safety trials, with multiple proposed kidney-protective mechanisms including anti-inflammatory, hemodynamic, and metabolic effects.
Mosterd, Charlotte M; Bjornstad, Petter; van Raalte, Daniël H · Review
Semaglutide subcutaneous was superior to dulaglutide and exenatide ER for HbA1c and weight reduction in head-to-head trials, with both semaglutide and dulaglutide showing cardiovascular and renal benefits.
Patel, Dhiren · Review
GLP-1 RAs (liraglutide, semaglutide, albiglutide, dulaglutide) reduce MACE in T2DM patients with CV disease, while DPP-4 inhibitors show CV safety but no MACE benefit, with saxagliptin increasing HF risk.
Patel, Kershaw V; Sarraju, Ashish; Neeland, Ian J; McGuire, Darren K · Review
Semaglutide demonstrated cardiovascular superiority in SUSTAIN 6, with a safety profile typical of GLP-1RAs. The only concerning signal was increased diabetic retinopathy events, likely related to rapid glucose lowering rather than direct drug toxicity.
Peter, Rajesh; Bain, Steve C · Review
Sotagliflozin ranked first for MACE (HR 0.76), heart failure hospitalization (HR 0.59), MI (HR 0.65), and stroke (HR 0.56). Empagliflozin and dapagliflozin led for kidney protection. Oral semaglutide and empagliflozin were best for all-cause death reduction.
Duan, Xue-Yan; Liu, Shu-Yan; Yin, Dao-Gen · Network Meta Analysis
Cagrilintide 2.4 mg plus semaglutide 2.4 mg achieved 17.1% body weight reduction at 20 weeks, with an estimated treatment difference of -7.4% versus semaglutide plus placebo (95% CI -11.2 to -3.5). No pharmacokinetic interactions between the drugs.
Enebo, Lone B; Berthelsen, Kasper K; Kankam, Martin; Lund, Michael T; Rubino, Domenica M; Satylganova, Altynai; Lau, David C W · Randomized Controlled Trial (Phase 1b)
Tirzepatide was noninferior and superior to semaglutide 1mg: HbA1c reductions of -2.01%, -2.24%, -2.30% (5/10/15mg) vs -1.86% semaglutide. Weight loss differences: -1.9, -3.6, -5.5 kg favoring tirzepatide (all p<0.001).
Frías, Juan P; Davies, Melanie J; Rosenstock, Julio; Pérez Manghi, Federico C; Fernández Landó, Laura; Bergman, Brandon K; Liu, Bing; Cui, Xuewei; Brown, Katelyn · Randomized Controlled Trial (Phase 3)
Oral semaglutide 14mg reduced total daily ad libitum energy intake by 38.9% versus placebo (treatment difference -5,096 kJ, p=0.0001). Increased satiety and fullness after fat-rich breakfast. Body weight decreased 2.7 kg (mostly fat mass) vs 0.1 kg placebo.
Gibbons, Catherine; Blundell, John; Tetens Hoff, Søren; Dahl, Kirsten; Bauer, Robert; Baekdal, Tine · Randomized Controlled Trial
15+ GLP-1-based compounds in clinical obesity development: mono-GLP-1 (semaglutide, PF-0688296, glutazumab), dual (tirzepatide, cotadutide, efinopegdutide, AMG 133), and multi-receptor (CagriSema, HM15211). Semaglutide positioned as the clinical benchmark.
Jepsen, Mathies M; Christensen, Mikkel B · Review
Oral semaglutide vs placebo: reduced HbA1c, weight, FPG, SMPG, serious adverse events, and all-cause death. Vs active comparators: reduced HbA1c, weight, SMPG. No increased hypoglycemia, MI, HF, stroke, or pancreatitis. Increased nausea, diarrhea, vomiting. 10 RCTs, 8,536 patients.
Li, Jingxin; He, Ke; Ge, Jun; Li, Caixia; Jing, Zeng · Meta Analysis
In a 72-week trial published in the New England Journal of Medicine, semaglutide at 0.4 mg daily achieved NASH resolution (without worsening fibrosis) in 59% of patients, compared to 17% on placebo (P<0.001). This was confirmed by liver biopsy — the gold standard for assessing liver disease. However, semaglutide did not significantly improve fibrosis: 43% of the 0.4 mg group had fibrosis improvement versus 33% on placebo (P=0.48, not significant). Patients on the highest dose lost an average of 13% of their body weight compared to 1% on placebo. GI side effects were common — 42% experienced nausea and 15% had vomiting at the 0.4 mg dose. A small neoplasm signal was noted (3 malignancies in semaglutide groups vs. 0 on placebo), though no pattern was evident.
Newsome, Philip N; Buchholtz, Kristine; Cusi, Kenneth; Linder, Martin; Okanoue, Takeshi; Ratziu, Vlad; Sanyal, Arun J; Sejling, Anne-Sophie; Harrison, Stephen A · Randomized Controlled Trial (Phase 2)
Semaglutide showed significantly higher signals for misuse-related adverse events compared to other GLP-1 drugs. Its proportional reporting ratios (PRR) for 'drug abuse' (4.05), 'drug withdrawal syndrome' (4.05), 'prescription drug used without a prescription' (3.60), and 'intentional product use issue' (1.80) were all significantly elevated (p<0.01) versus other GLP-1 receptor agonists. However, when compared to the phentermine-topiramate combination (an established weight loss drug with known misuse potential), semaglutide showed no significant differences in misuse signals. This suggests semaglutide's misuse signal may be in line with other weight loss medications rather than uniquely problematic.
Chiappini, Stefania; Vickers-Smith, Rachel; Harris, Daniel; Papanti Pelletier, G Duccio; Corkery, John Martin; Guirguis, Amira; Martinotti, Giovanni; Sensi, Stefano L; Schifano, Fabrizio · Pharmacovigilance / Database Analysis
Analysis of 22,287 adverse event reports from the FDA's FAERS database revealed distinct side effect profiles depending on whether semaglutide was given by injection or taken orally. Subcutaneous injection was more likely to cause endocrine-related adverse events, while oral semaglutide was more likely to trigger gastrointestinal side effects. Notably, oral administration also accelerated the onset of adverse reactions compared to injection. The study compared 16,346 subcutaneous injection reports against 2,496 oral administration reports from Q4 2017 through Q4 2023.
Niu, Kaibin; Fan, Maoxia; Gao, Wulin; Chen, Chen; Dai, Guohua · Pharmacovigilance
When semaglutide supply shortages hit Australia in 2022, prescriptions dropped 17% while dulaglutide prescriptions surged 53% as doctors switched patients to the available alternative. The shortages resulted in approximately 119,069 fewer semaglutide prescriptions than predicted over a 4-month period. When dulaglutide also experienced shortages shortly after, its prescriptions dropped 17% as well, leaving type 2 diabetes patients with limited GLP-1 agonist options.
Phakey, Sachin; Shen, Angeline · Retrospective Analysis
Among people with type 2 diabetes, semaglutide was linked to a lower risk of medical encounters related to tobacco use disorder compared to other diabetes drug classes. The effect was strongest when comparing semaglutide to insulin. It was weakest compared to other GLP-1 receptor agonists, suggesting the effect may be partly a GLP-1 class effect rather than unique to semaglutide. Semaglutide users also had fewer prescriptions for smoking cessation medications and less counseling for smoking. These patterns held regardless of whether patients were also obese.
Popovic, Djordje S; Patoulias, Dimitrios; Koufakis, Theocharis; Karakasis, Paschalis; Ruža, Ieva; Papanas, Nikolaos · Review/Commentary
Both exendin-4 and semaglutide improved outcomes when given right after brain injury in newborn mice. The drugs reduced the size of the damaged brain area, increased survival rates, and improved locomotor function in both short-term and long-term assessments. The mechanism involved upregulation of the PI3K/AKT signaling pathway (a cell survival pathway) and increased cAMP levels (a molecule that helps cells communicate). The drugs also reduced inflammation after oxygen-glucose deprivation in brain cells.
Poupon-Bejuit, Laura; Geard, Amy; Millicheap, Nathan; Rocha-Ferreira, Eridan; Hagberg, Henrik; Thornton, Claire; Rahim, Ahad A · Animal Study
Semaglutide outperformed dulaglutide in both HbA1c reduction and weight loss, making it the most sought-after GLP-1 drug. Clinicians began prescribing Ozempic (semaglutide for diabetes) off-label for weight loss, even though Wegovy (semaglutide for weight) existed. This drove shortages. Insurance companies responded by requiring prior authorizations proving a type 2 diabetes diagnosis before covering these drugs. The commentary notes that most insurance plans still do not cover GLP-1 drugs solely for weight management, pushing weight-loss demand onto the diabetes supply chain.
Powell, Jason; Taylor, James · Review/Commentary
PPAR agonists work by making cells more sensitive to insulin. Pioglitazone (a PPARγ agonist) and saroglitazar (a PPARα/γ agonist) are recommended by several medical groups for treating fatty liver in diabetes. Newer PPAR drugs like elafibranor and lanifibranor are also showing promise. GLP-1 receptor agonists take a different approach. They produce significant weight loss and may directly reduce liver inflammation and fibrosis (scarring). The review notes that dual-agonists (like tirzepatide targeting GIP/GLP-1) and triple-agonists have produced even more impressive weight loss, which could further benefit the liver. However, direct evidence of liver benefit from these newer multi-agonists is still limited.
Pramanik, Subhodip; Pal, Partha; Ray, Sayantan · Review
Semaglutide reduced the composite outcome of heart failure events or cardiovascular death (HR 0.73, meaning a 27% reduction, p = 0.0005). When broken down, it reduced heart failure events alone by 27% (HR 0.73, p = 0.0068) and cardiovascular death alone by 29% (HR 0.71, p = 0.0036). About 19% of participants had heart failure at baseline. The benefit was consistent in both groups: those with pre-existing heart failure (HR 0.73, p = 0.034) and those without (HR 0.72, p = 0.003). Patients with more severe heart failure (NYHA class III) and reduced ejection fraction had higher overall event rates regardless of treatment.
Pratley, Richard E; Tuttle, Katherine R; Rossing, Peter; Rasmussen, Søren; Perkovic, Vlado; Nielsen, Olav Wendelboe; Mann, Johannes F E; MacIsaac, Richard J; Kosiborod, Mikhail N; Kamenov, Zdravko; Idorn, Thomas; Hansen, Marco Bo; Hadjadj, Samy; Bakris, George; Baeres, Florian M M; Mahaffey, Kenneth W · Randomized Controlled Trial
Among diabetes medications studied for stroke prevention, GLP-1 receptor agonists (specifically semaglutide and dulaglutide) reduced the risk of ischemic stroke in people with type 2 diabetes. Pioglitazone significantly reduced recurrent stroke risk. DPP-4 inhibitors, SGLT2 inhibitors, and insulin did not affect stroke incidence. Metformin monotherapy showed possible stroke reduction but evidence was less definitive.
Prentza, Vasiliki; Pavlidis, George; Ikonomidis, Ignatios; Pililis, Sotirios; Lampsas, Stamatios; Kountouri, Aikaterini; Pliouta, Loukia; Korakas, Emmanouil; Thymis, John; Palaiodimou, Lina; Tsegka, Aikaterini; Markakis, Konstantinos; Halvatsiotis, Panagiotis; Tsivgoulis, Georgios; Lambadiari, Vaia · Systematic Review
The researchers created a microphysiological system (MPS), a tiny interconnected network of human fat cells, liver cells, and inflammatory immune cells (macrophages). When macrophages inflamed the fat cells, the liver cells accumulated fat and stopped responding to insulin properly. This recreated the early stages of metabolic dysfunction-associated steatotic liver disease (MASLD, previously called NAFLD). Semaglutide improved liver cell function in this system. The key discovery: semaglutide acted on the fat cells, not the liver cells. By calming the inflamed fat cells, semaglutide indirectly reduced liver fat accumulation and restored insulin sensitivity throughout the system.
Qi, Lin; Groeger, Marko; Sharma, Aditi; Goswami, Ishan; Chen, Erzhen; Zhong, Fenmiao; Ram, Apsara; Healy, Kevin; Hsiao, Edward C; Willenbring, Holger; Stahl, Andreas · In Vitro
In the SUSTAIN-6 cardiovascular outcome trial, semaglutide was associated with approximately 75% increased risk of diabetic retinopathy (DR) worsening. This was a secondary endpoint, not the trial's primary focus. Cases were rare in absolute terms. Insulin icodec (a novel once-weekly insulin) also showed increased DR worsening compared to daily insulin. No other recent antihyperglycemic agent (SGLT2 inhibitors, DPP-4 inhibitors, other GLP-1 drugs) was associated with DR worsening. Importantly, after the SUSTAIN-6 finding, nearly all subsequent trials excluded patients with pre-existing diabetic retinopathy. This means the true risk in the most vulnerable population remains unclear. Dedicated semaglutide eye safety studies were underway at the time of publication. The most at-risk patients are those with pre-existing high-risk DR, poor baseline blood sugar (where rapid improvement could trigger worsening), and those using insulin.
Rajagopal, Rithwick; McGill, Janet B · Review
Sixteen obese patients with IBD (9 Crohn's disease, 7 ulcerative colitis) received semaglutide 1.0 mg or liraglutide 3.0 mg for obesity. Their median starting BMI was 35. At 6 months, median weight change was -6.2%. 58.3% (7 of 12 evaluable patients) achieved at least 5% weight loss. IBD activity scores showed no significant changes during follow-up, meaning the drugs did not trigger disease flares. Side effects were mild. Nausea was the most common at 13.3%. One patient discontinued due to diarrhea. No serious adverse events were reported.
Ramos Belinchón, Clara; Martínez-Lozano, Helena; Serrano Moreno, Clara; Hernández Castillo, Diego; Lois Chicharro, Pablo; Ferreira Ocampo, Pablo; Marín-Jiménez, Ignacio; Bretón Lesmes, Irene; Menchén, Luis · Case Series
Semaglutide search interest increased dramatically from 2022 onward across most of the 27 countries studied. The US and Canada had the largest and most sustained interest. Natural language processing of search queries revealed that weight loss was the dominant theme in most countries. A diabetes theme was generally absent or weak, confirming that public interest is driven by weight loss rather than the drug's original purpose. Media coverage partially explained search interest (Granger causality analysis), with the UK and Germany showing strong relationships between news reports and subsequent search spikes. A single Dr. Oz TV episode coincided with search peaks across multiple countries. Some countries showed concerning themes: Australia, Chile, South Africa, and the UK had searches for buying Ozempic from specific retailers, and Germany had searches for obtaining it without a prescription.
Raubenheimer, Jacques Eugene; Myburgh, Pieter Hermanus; Bhagavathula, Akshaya Srikanth · Infodemiological
GLP-1 receptor agonists work by mimicking the natural gut hormone GLP-1, which reduces appetite and slows stomach emptying. Semaglutide and liraglutide are the two GLP-1 drugs FDA-approved for weight management. Beyond weight loss, these drugs show early evidence of cardiovascular benefits in obese patients, including reduced cardiovascular events and improved risk factors. The SELECT trial showed semaglutide reduced major cardiovascular events by 20% in obese people without diabetes. Common side effects are gastrointestinal (nausea, vomiting, diarrhea) and are usually mild to moderate. The review discusses strategies for managing these effects, including gradual dose escalation.
Raza, Fatima Ali; Altaf, Rafiya; Bashir, Talha; Asghar, Fatima; Altaf, Rabiya; Tousif, Sohaib; Goyal, Aman; Mohammed, Aisha; Mohammad, Mahnoor Faisal; Anan, Mahfuza; Ali, Sajjad · Review
Semaglutide produced significant improvements in patients with HFpEF and obesity: - 6-minute walk distance: improved by 15.1 meters vs placebo (95% CI 5.8-24.4, p = 0.002) - Body weight: reduced by 2.9% vs placebo (95% CI -4.1 to -1.7, p = 0.001) - C-reactive protein: reduced (indicating lower inflammation) - Several secondary clinical endpoints also improved - Adverse events: generally well-tolerated with no unexpected safety concerns
Rehman, Ayesha; Saidullah, Shahab; Asad, Muhammad; Gondal, Umer R; Ashraf, Amna; Khan, Muhammad F; Akhtar, Waheed; Mehmoodi, Amin; Malik, Jahanzeb · Retrospective Cohort
Albuminuria was more consistently reduced by semaglutide than eGFR. The benefit was strongest in patients with macroalbuminuria (heavy protein loss). This suggests semaglutide may help slow the progression of diabetic kidney disease by reducing the protein that damages kidney filters. However, the impact on eGFR was variable. Some studies showed improvement, others showed no change, and some showed decrease. This inconsistency could reflect differences in patient populations, disease severity, and follow-up duration. Two case reports described acute kidney injury (AKI) associated with semaglutide, including one case of acute interstitial nephritis. This highlights the need for kidney monitoring during therapy, particularly in patients with advanced chronic kidney disease.
Rehman, Shuja Ur; Kolanu, Nikhil Deep; Mushtaq, Muhammad Muaz; Ali, Husnain; Ahmed, Zeeshan; Mushtaq, Maham; Liaqat, Maryyam; Sarwer, Muhammad Asad; Bokhari, Syed Faqeer Hussain; Ahmed, Fazeel; Bakht, Danyal · Systematic Review
Anti-obesity drugs, particularly GLP-1 receptor agonists, may have potential for treating binge eating disorder, but current evidence is limited and the psychological components of BED require special attention.
Riboldi, Ilaria; Carrà, Giuseppe · Review
GLP-1 receptor agonists protect kidneys through anti-inflammatory, antioxidant, and anti-fibrotic mechanisms, with clinical data from the FLOW trial confirming semaglutide slows kidney disease progression.
Rico-Fontalvo, Jorge; Reina, Maricely; Soler, María José; Unigarro-Palacios, Mario; Castañeda-González, Juan Pablo; Quintero, Javier Jiménez; Raad-Sarabia, María; Moraes, Thyago Proença de; Daza-Arnedo, Rodrigo · Review
Semaglutide does not increase cardiovascular adverse events or mortality but is associated with higher rates of gastrointestinal side effects compared to placebo.
Rivera, Frederick Berro; Arias-Aguirre, Eloise; Aguirre, Zedrick; Ybañez, Mc John C; Rubia, Janos Marc M; Galang, Danica Janine; Lumbang, Grace Nooriza; Ruyeras, Jade Monica Marie J; Magalong, John Vincent; Pine, Polyn Luz; Amigo, John Andrew C; Ansay, Marie Francesca M; Zelenkov, Nenad; Thomas, Steve Samuel; Vijayaraghavan, Krishnaswami · Meta Analysis
Semaglutide and phentermine/topiramate showed the most consistent long-term weight loss among veterans, with data extending up to 48 months.
Rodriguez, Allison D; Ifeachor, Amanda P; Moore, Emily A; Otte, Cassandra F; Schopper, M Joseph; Liangpunsakul, Suthat; Lteif, Amale A · Cohort
Tirzepatide produced greater on-treatment weight loss than semaglutide in adults with overweight or obesity in a real-world clinical setting, with comparable gastrointestinal side effect rates.
Rodriguez, Patricia J; Goodwin Cartwright, Brianna M; Gratzl, Samuel; Brar, Rajdeep; Baker, Charlotte; Gluckman, Ty J; Stucky, Nicholas L · Cohort
Both oral and subcutaneous semaglutide significantly reduced fat mass and improved metabolic parameters in adults with obesity and type 2 diabetes over 24 weeks.
Rodríguez Jiménez, Beatriz; Rodríguez de Vera Gómez, Pablo; Belmonte Lomas, Samuel; Mesa Díaz, Ángel Manuel; Caballero Mateos, Irene; Galán, Irene; Morales Portillo, Cristóbal; Martínez-Brocca, María Asunción · Cohort
Current FDA guidance for evaluating generic peptide drug sameness needs clarification on higher order structure assessment to ensure generic peptide drugs are safe and effective.
Rogers-Crovak, Jessica A; Delaney, Edward J; Detlefsen, David J · Review
Semaglutide 2.4 mg produced significant and consistent weight loss across racial and ethnic subgroups in the STEP trials, with comparable safety profiles.
Rubino, Domenica; Angelene, Hanna; Fabricatore, Anthony; Ard, Jamy · RCT
Disproportionality analysis of the European Pharmacovigilance database found no elevated signal for suicidal events with GLP-1 receptor agonists as a class.
Ruggiero, Rosanna; Mascolo, Annamaria; Spezzaferri, Angela; Carpentieri, Claudia; Torella, Daniele; Sportiello, Liberata; Rossi, Francesco; Paolisso, Giuseppe; Capuano, Annalisa · Cohort
Semaglutide reduced incident atrial fibrillation by 42% (RR 0.58, 95% CI 0.40–0.85) with no heterogeneity across studies (I² = 0%). The benefit was consistent between oral semaglutide (RR 0.53) and subcutaneous semaglutide (RR 0.59), with no significant difference between routes (p = 0.83). Meta-regression showed no influence of diabetes proportion (p = 0.14) or BMI (p = 0.60) on the effect.
Saglietto, Andrea; Falasconi, Giulio; Penela, Diego; Francia, Pietro; Sau, Arunashis; Ng, Fu Siong; Dusi, Veronica; Castagno, Davide; Gaita, Fiorenzo; Berruezo, Antonio; De Ferrari, Gaetano Maria; Anselmino, Matteo · Meta Analysis
Semaglutide users had significantly higher rates of increased residual gastric content (20.3% vs 3.2%, p<0.001). Discontinuation >21 days in patients with digestive symptoms and >14 days in those without symptoms resulted in RGC comparable to non-users (OR 0.77, 95% CI 0.22-2.01).
Santos, Leonardo Barbosa; Mizubuti, Glenio B; da Silva, Leopoldo Muniz; Silveira, Saullo Queiroz; Nersessian, Rafael Souza Fava; Abib, Arthur de Campos Vieira; Bellicieri, Fernando Nardy; Lima, Helidea de Oliveira; Ho, Anthony M-H; Dos Anjos, Gabriel Silva; de Moura, Diogo Turiani Hourneaux; de Moura, Eduardo Guimarães Hourneuax; Vieira, Joaquim Edson · Cohort
Oral semaglutide reduced HbA1c by 1.1 percentage points (95% CI -1.27 to -0.96, P<0.001) and body weight by 4.4 kg in real-world UK clinical practice. 36.4% achieved combined HbA1c reduction plus ≥3% weight loss; 27.1% achieved HbA1c reduction plus ≥5% weight loss. No severe hypoglycemia or new safety signals.
Saravanan, Ponnusamy; Bell, Heather; Braae, Uffe Christian; Collins, Edward; Deinega, Alisa; Dhatariya, Ketan; Machell, Alena; Trent, Antonia; Strzelecka, Anna · Cohort
Dose escalation from 7 mg to 14 mg oral semaglutide produced a significant additional HbA1c reduction of -0.5 ± 0.8% (from 7.4% to 7.0%, p<0.01) and weight loss of -2.0 ± 4.4 kg (p<0.01) over 24 weeks. 41% of patients achieved ≥3% weight reduction. GI disorders occurred in 10.6% (nausea 7.6%), all mild-moderate.
Sato, Genki; Uchino, Hiroshi; Hirose, Takahisa · Cohort
Second-generation anti-obesity medications achieve ~15% average weight loss with lifestyle modifications. Three approved drugs: setmelanotide (monogenic obesity), semaglutide 2.4 mg, and tirzepatide. Semaglutide and tirzepatide are particularly effective when treating concurrent obesity and T2D.
Schmitz, Sarah H; Aronne, Louis J · Review
Hydrogel microsphere-semaglutide showed an in vivo release half-life of ~36 days in mice. A single subcutaneous dose produced 20% lean-sparing body weight loss over one month, statistically equivalent to twice-daily semaglutide. Pharmacokinetic simulations predicted once-monthly human dosing with Cmin matching weekly dosing but only 75% of the Cmax, potentially reducing adverse effects.
Schneider, Eric L; Hangasky, John A; Fernández, Rocío Del Valle; Ashley, Gary W; Santi, Daniel V · Animal Study