Peptide Research Database
Access 7,186 peer-reviewed studies, clinical trials, and research papers on peptides. Filter by key research, study type, compound, and category. Direct links to full PubMed entries for comprehensive, evidence-based exploration.
Medications for adults with type 2 diabetes: a living systematic review and network meta-analysis.
In a research review of 869 trials and nearly 500,000 people with type 2 diabetes, researchers ranked 13 drug classes by benefits and risks. GLP-1 drugs and SGLT2 inhibitors stood out for reducing heart problems, kidney disease, and death, while also helping with weight loss and blood sugar control.
Nong K, Jeppesen BT, Shi Q, Agoritsas T, Guyatt GH, White H, Gao Y, Agarwal A, Macdonald H, Zou X, Millard T, Schnell O, Marx N, Brosius FC, McDonald S, Quigley M, Tian X, Fan Q, White B, Mao Y, Pan X, Liu C, Zhai C, Yuan C, Li Q, An J, Gan Y, Wang Y, Jin Y, Sun F, Zhu Z, Rydén L, Standl E, Turner T, Vandvik PO, Li S
To provide up-to-date evidence on key benefits, harms, and uncertainties regarding medications for adults with type 2 diabetes. Living systematic review and network meta-analysis (NMA), using frequentist random effects and GRADE (grading of recommendations, assessment, development and evaluation) approaches. Updates are planned at least two times a year. Medline and Embase, searched up to 31 July 2024 for the current iteration. Randomised controlled trials of at least 24 weeks comparing one or more medications with standard treatment, placebo, or each other. The systematic review and NMA includes 493 168 participants from 869 trials (adding 53 trials since October 2022) reporting data for 13 drug classes (63 drugs) and 26 outcomes of interest. Regarding benefits, moderate to high certainty evidence confirms the well established cardiovascular and kidney benefits of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and finerenone (the last for patients with established chronic kidney disease). The most effective drugs in reducing body weight were tirzepatide (mean difference (MD) -8.63 kg (95% confidence interval -9.34 to -7.93); moderate certainty) and orforglipron (MD -7.87 kg (-10.24 to -5.50); low certainty), followed by eight other GLP-1RAs (high to moderate certainty). Absolute benefits of medications vary substantially depending on the baseline risk of cardiovascular and kidney outcomes; risk-stratified absolute effects of medications are summarised using an interactive multiple comparisons tool (https://matchit.magicevidence.org/250709dist-diabetes/#!/). Regarding medication-specific harms, SGLT-2 inhibitors increase genital infections (odds ratio (OR) 3.29 (95% CI 2.88 to 3.77); high certainty) and ketoacidosis due to diabetes (OR 2.08 (1.45 to 2.99); high certainty), and probably increase amputations (OR 1.27 (1.01 to 1.61); moderate certainty); tirzepatide and GLP-1RAs probably increase severe gastrointestinal events (most increased risk with tirzepatide (OR 4.21 (1.87 to 9.49); moderate certainty)); finerenone increases severe hyperkalaemia (OR 5.92 (3.02 to 11.62); high certainty); and thiazolidinediones increase major osteoporotic fractures and probably increase hospitalisation for heart failure. Sulfonylureas, insulin, and dipeptidyl peptidase-4 inhibitors probably increase the risk of severe hypoglycaemia. There is low to very low certainty evidence for effects on other diabetes-related complications, including neuropathy and visual impairment. Despite interest in the issue, there is uncertainty about whether GLP-1RAs may reduce dementia (OR 0.92 (0.83 to 1.02); low certainty). This living systematic review provides a comprehensive summary of the cardiovascular, kidney, and weight loss benefits, as well as medication-specific harms of medications for adults with type 2 diabetes, including effects of SGLT-2 inhibitors, GLP-1RAs, finerenone and tirzepatide. PROSPERO number: CRD42022325948. A more detailed protocol is available at https://data.aliveevidence.org/records/q02rv-km486. This article is the first version of a living systematic review. It is linked to a living BMJ Rapid Recommendation and other living clinical practice guidelines, presenting risk stratified recommendations for patients with type 2 diabetes at lower, moderate, and higher risk of cardiovascular and kidney complications. The latest evidence will be made available via the BMJ Rapid Recommendation and via an interactive GRADE evidence summary (MATCH-IT: https://matchit.magicevidence.org/250709dist-diabetes/#!/). Major updates will be published in The BMJ.
Discontinuing glucagon-like peptide-1 receptor agonists and body habitus: A systematic review and meta-analysis.
In a research review of studies on GLP-1 weight loss drugs, patients who stopped taking the medication regained most of the weight they had lost. This finding highlights that GLP-1 drugs may need to be taken long-term to maintain results, similar to how blood pressure medication only works while you take it.
Berg S, Stickle H, Rose SJ, Nemec EC
Research on Glucagon-like peptide 1 receptor agonist (GLP-1RA) has mainly focused on the efficacy of weight loss and not the long-term efficacy of weight loss maintenance. This systematic review and meta-analysis aims to evaluate the sustainability of weight loss of patients taking GLP-1RAs following the discontinuation of the drug. EBSCOhost was used to simultaneously search Academic Search Premier, CINHAL Ultimate, Cochrane Central Register of Controlled Trials, MEDLINE with full text, Cochrane Database of Systematic Reviews, and separate PubMed search was systematically investigated using a predetermined search strategy from inception to February 1st, 2024. The authors extracted data regarding body weight change from baseline on treatment and off treatment, change in waist circumference from baseline on and off treatment, and change in BMI from baseline on and off treatment. Meta-analysis was conducted using RevMan (version 5.4) to calculate pooled mean differences using a Der Simonian-Laird Random Effects model. ResultsThe initial search yielded 497 relevant articles and, after screening, retained 8 randomized controlled trials comprised of 2372 participants, all with a BMI ≥ 27 kg/m2. After discontinuing GLP-1RA therapy, weight regain was proportional to the original weight loss. Participants who took liraglutide regained 2.20 kg (95% CI 1.69 to 2.70, P < 0.00001), and participants taking semaglutide/tirzepatide regained 9.69 kg (95% CI 5.78 to 13.60, P < 0.00001). This systematic review and meta-analysis show that significant weight is regained after discontinuing GLP-1RA treatment, which should be discussed when stopping therapy. PRACTITIONER POINTS: Question: Does discontinuation of Glucagon-like peptide 1 receptor agonist (GLP-1RA) treatment lead to significant weight gain? Findings: In this systematic review and meta-analysis, discontinuing GLP-1RA treatment led to a pooled overall mean weight regain of 2.20 kg in participants taking liraglutide and 9.69 kg in those patients prescribed semaglutide/tirzepatide. The proportion of weight regained was proportional to the amount originally lost. Meaning: Discontinuation of GLP-1RA treatment leads to weight regain, regardless of lifestyle interventions, and should therefore be considered a chronic therapy to prevent weight regain and associated undesirable outcomes related to obesity.
Cardiovascular and Kidney Outcomes and Mortality With Long-Acting Injectable and Oral Glucagon-Like Peptide 1 Receptor Agonists in Individuals With Type 2 Diabetes: A Systematic Review and Meta-analysis of Randomized Trials.
In a research review including new data from the SOUL and FLOW trials, both injectable and oral forms of long-acting GLP-1 drugs reduced heart attacks, strokes, and death in people with type 2 diabetes. The oral version of semaglutide showed heart and kidney benefits similar to the injectable form, which could mean more treatment options for patients.
Lee MMY, Sattar N, Pop-Busui R, Deanfield J, Emerson SS, Inzucchi SE, Mann JFE, Marx N, Mulvagh SL, Poulter NR, Badve SV, Pratley RE, Perkovic V, Buse JB, McGuire DK
Glucagon-like peptide 1 receptor agonists (GLP-1RA) reduce the incidence of major adverse cardiovascular events (MACE) in type 2 diabetes (T2D), although whether benefits extend to both subcutaneous and oral formulations remains unclear. In these meta-analyses, including new data from the Semaglutide cardiOvascular oUtcomes triaL (SOUL) (oral semaglutide) and Evaluate Renal Function with Semaglutide Once Weekly (FLOW) trial, we examined cardiovascular (CV) and kidney benefits and risks of long-acting (defined as having pharmacokinetics sufficient to provide 24-h activity) GLP-1RA in T2D. A systematic review of PubMed was conducted (to 7 February 2025). Randomized placebo-controlled CV and kidney outcomes trials of GLP-1RA with ≥500 individuals with T2D were included. A random-effects model was used to estimate hazard ratios (HRs) for MACE, its components, all-cause mortality, hospitalization for heart failure (HHF), a composite kidney outcome (kidney failure [kidney replacement therapy or persistent estimated glomerular filtration rate [eGFR] <15 mL/min/1.73 m2], sustained ≥50% eGFR decline or nearest equivalent, or kidney-related death), worsening kidney function, and safety outcomes. Across 10 trials (n = 71,351), long-acting GLP-1RA reduced incidence rate of MACE by 14% (HR 0.86 [95% CI 0.81, 0.90]; I2 = 27.6%), HHF by 14% (0.86 [0.79, 0.93]; I2 = 2.1%), and the composite kidney outcome by 17% (0.83 [0.75, 0.92]; I2 = 20.4%) and all-cause mortality by 12% (0.88 [0.82, 0.93]; I2 = 17.5%). A consistent 14% reduction was seen for all MACE components. There was no significant heterogeneity by GLP-1RA administration route (subcutaneous vs. oral). There were no increased risks of severe hypoglycemia, retinopathy, or pancreatic events. Trial-level meta-analyses preclude detailed subgroup analyses and may introduce ecological bias. As a group, long-acting GLP-1RA, including both injectable and oral formulations, reduce incidence of MACE, HHF, and kidney events and all-cause mortality in T2D.
Comparison of pharmacological therapies in metabolic dysfunction-associated steatohepatitis for fibrosis regression and MASH resolution: Systematic review and network meta-analysis.
In a research review comparing drugs for fatty liver disease (MASH), researchers ranked which medications best reversed liver scarring and resolved the disease. This analysis helps doctors understand which of the many new treatments in development are most promising for a condition that currently has very few approved options.
Souza M, Al-Sharif L, Antunes VLJ, Huang DQ, Loomba R
Metabolic dysfunction-associated steatohepatitis (MASH) is a leading cause of liver disease. With the advent of multiple therapeutic targets in late-phase clinical drug development for MASH, there is a knowledge gap to better understand the comparative efficacy of various pharmacological agents. We conducted an updated network meta-analysis to evaluate the relative rank order of the different pharmacological agents for both fibrosis regression and MASH resolution. We searched PubMed and Embase databases from January 1, 2020 to December 1, 2024, for published randomized controlled trials comparing pharmacological interventions in patients with biopsy-proven MASH. The co-primary endpoints were fibrosis improvement ≥1 stage without MASH worsening and MASH resolution without worsening fibrosis. We conducted surface under the cumulative ranking curve (SUCRA) analysis. A total of 29 randomized controlled trials (n=9324) were included. Pegozafermin, cilofexor + firsocostat, denifanstat, survodutide, obeticholic acid, tirzepatide, resmetirom, and semaglutide were significantly better than placebo in achieving fibrosis regression without worsening MASH. Pegozafermin (SUCRA: 79.92), cilofexor + firsocostat (SUCRA: 71.38), and cilofexor + selonsertib (SUCRA: 69.11) were ranked the most effective interventions. Pegozafermin, survodutide, tirzepatide, efruxifermin, liraglutide, vitamin E + pioglitazone, resmetirom, semaglutide, pioglitazone, denifanstat, semaglutide, and lanifibranor were significantly better than placebo in achieving MASH resolution without worsening fibrosis. Pegozafermin (SUCRA: 91.75), survodutide (SUCRA: 90.87), and tirzepatide (SUCRA: 84.70) were ranked the most effective interventions for achieving MASH resolution without worsening fibrosis. This study provides updated rank-order efficacy of MASH pharmacological therapies for fibrosis regression and MASH resolution. These data are helpful to inform practice and clinical trial design.
Cardiovascular Effects and Tolerability of GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis of 99,599 Patients.
In a research review of 21 trials covering nearly 100,000 patients, GLP-1 drugs significantly reduced the risk of heart attacks, strokes, and heart-related death. The benefits held across different patient groups, including people with and without diabetes, and the drugs were generally well-tolerated aside from common gut-related side effects like nausea.
Galli M, Benenati S, Laudani C, Simeone B, Sarto G, Ortega-Paz L, Rocco E, Bernardi M, Spadafora L, D'Amario D, Greco E, Frati G, Federici M, Mehran R, Crea F, Angiolillo DJ, Sciarretta S
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated significant cardiovascular (CV) benefits, particularly in patients with diabetes mellitus, but the safety and efficacy of different GLP-1 RAs across diverse populations remain insufficiently defined. Previous meta-analyses of GLP-1 RAs have been limited by restricted populations, omission of recent trials, or incomplete safety synthesis; this study integrates the latest evidence across 21 randomized controlled trials and diverse populations using advanced meta-analytic methods. Randomized controlled trials comparing GLP-1 RAs vs controls or placebo were included. Analyses were conducted in prespecified subgroups based on the GLP-1 RA used. Prespecified subgroups according to diabetes mellitus, kidney function, obesity, or heart failure were also performed. Main outcomes comprised mortality (all-cause and CV), trial-defined major adverse cardiovascular events (MACE) and serious adverse events. GRADE (Grading of Recommendations Assessment, Development and Evaluation) and trial sequential analyses were performed to evaluate certainty and conclusiveness of findings, respectively. A total of 21 trials encompassing 99,599 patients were included. Eight different GLP-1 RAs were used (lixisenatide, liraglutide, exenatide, semaglutide, efpeglenatide, dulaglutide, albiglutide, and tirzepatide), each administered at therapeutic doses and compared vs placebo or controls. Mean follow-up duration was 2.4 years. We found conclusive, high-certainty evidence that GLP-1 RAs reduced all-cause death (incidence rate ratio [IRR]: 0.88; 95% CI: 0.84-0.92; needed to treat [NNT] = 121), CV death (IRR: 0.87; 95% CI: 0.81-0.92; NNT = 170), and MACE (IRR: 0.87; 95% CI: 0.83-0.91; NNT = 66), compared with controls. GLP-1 RAs reduced serious adverse events (-9%), myocardial infarction (-15%), acute kidney failure (-9%), heart failure (-15%), and infections (-10%), but increased gastrointestinal (+63%) and gallbladder (+26%) disorders. There were no differences in stroke, pancreatitis, or neoplasm between groups. Results were mostly consistent across subgroups. Analysis by GLP-1 RA type revealed potential differences in efficacy and safety profiles. GLP-1 RAs reduce mortality and MACE in high-risk populations, highlighting benefits beyond glycemic control. These come at increased gastrointestinal and gallbladder risks. Variation in efficacy and tolerability supports tailoring GLP-1 RA therapy to individual patient characteristics and treatment goals. (PROSPERO [GLP-1 RAs Reduce Mortality and Cardiovascular Events Across the Spectrum of Treated Patients: A Systematic Review and Meta-Analysis]; CRD420251032222).