Peptide Research Database

Effect of GLP-1 receptor agonist on nutrient intake: A narrative review.

In a research review, given the side effects of GLP-1 receptor agonists and their intended appetite suppression, clinicians' nutritional counseling and treatment become invaluable.

Fujioka K

Humans have a primitive defense mechanism called metabolic adaptation that slows voluntary weight loss. It works by downregulating hormones that reduce food intake and by lowering the metabolic rate. Second-generation GLP-1 receptor agonists, such as semaglutide or tirzepatide, promote weight loss by targeting this hormonal system to control appetite. Appetite can be divided into hunger, satiety, satiation, and reward eating. This review will examine how GLP-1 receptor agonists and newer satiety hormone agonists influence appetite and its components. Research indicates that these new satiety hormone agonists significantly reduce meal size and may decrease overall water intake. Additionally, the choice of highly palatable foods is affected and may extend to alcohol consumption. Clinicians need to understand how these new drugs affect food intake to counsel patients effectively. Most patients will experience gastrointestinal side effects, which can often be managed with dietary adjustments. Other clinical issues stemming from the substantial decrease in food intake will also need to be monitored. Loss of lean tissue, including bone and muscle, has been reported. Clinicians can adjust dosing of these medications but will need to make nutritional adjustments to help mitigate these effects. Now that these powerful weight-loss agents have been available for several years, vitamin deficiencies have been reported. Given the side effects of GLP-1 receptor agonists and their intended appetite suppression, clinicians' nutritional counseling and treatment become invaluable.

Semaglutide and Limb Events: Expanding the Cardiovascular Prevention Paradigm?

Canonico ME, Bonaca MP

The NAD+ challenge: Harnessing immune-mediated tumor control without fueling the enemy.

Zuiker E, Hemann EA, Long ME

Comparing Cardiovascular Outcomes in New Users of Oral Semaglutide Versus Other Noninsulin Glucose-Lowering Therapies Among Adults with Type 2 Diabetes and Atherosclerotic Cardiovascular Disease.

In a clinical study, consistent with clinical trial evidence, oral semaglutide was associated with a lower risk of heart health among people with T2D and ASCVD in real-world settings.

Tan X, Liang Y, Zhong C, Xie L, Guevarra M, Swift C, de Havenon A

Clinical trials have found semaglutide reduces the risk of major adverse cardiovascular events (MACE) among people with type 2 diabetes (T2D) at high risk of MACE. Less is known about oral semaglutide's impact on real-world cardiovascular risk. This observational cohort study used administrative claims data from Optum's deidentified Clinformatics® Data Mart Database to compare 3-, modified 3-, 5-, modified 5-, and 2-point MACE, ischemic stroke (IS), myocardial infarction (MI), and all-cause and cardiovascular-related death rates among people with T2D and atherosclerotic cardiovascular disease (ASCVD) who initiated oral semaglutide vs other noninsulin glucose-lowering therapies (ONIGLTs). Cardiovascular outcomes were compared between new users of oral semaglutide and propensity score-matched new users of dipeptidyl peptidase 4 inhibitors (DPP4is) or sodium-glucose cotransporter 2 inhibitors (SGLT2is). Oral semaglutide users (n = 10,878) had risk reductions of 17% and 21% in 3- and modified 3-point MACE, respectively, and significant risk reductions in 5-, modified 5-, and 2-point MACE, IS, and all-cause death vs ONIGLT users (n = 28,639). People who initiated oral semaglutide (n = 7218) had 22% and 24% lower risks of 3- and modified 3-point MACE, respectively, and significantly lower risks of 5- and modified 5-point MACE, IS, and all-cause death vs people who initiated DPP4is (n = 7218). Compared with SGLT2i users (n = 21,572), oral semaglutide users (n = 7491) had 21% and 22% lower risks of 3- and modified 3-point MACE, respectively, and significantly lower risks of 5-, modified 5-, and 2-point MACE. Consistent with clinical trial evidence, oral semaglutide was associated with a lower risk of cardiovascular outcomes among people with T2D and ASCVD in real-world settings.

Semaglutide as adjunct treatment for obesity in adolescents receiving antipsychotic medication (the GOAL trial): protocol for a single-arm, open-label feasibility study.

In a clinical study, 2024-5 17 471-21-02.

Giraldi LV, Andersen JT, Jespersen J, Baden CS, Fonvig CE, Riis T, Dalhoff KP, Holm JC, Fink-Jensen A, Pagsberg AK, Christensen MB, Gade C

Adolescents treated with antipsychotic medication are at increased risk of obesity and metabolic complications, yet evidence-based interventions in this group remain limited. Glucagon-like peptide-1 receptor agonists have demonstrated efficacy in the treatment of obesity in both adults and adolescents. The aim of this trial is to assess the feasibility of a 36-week treatment period with a glucagon-like peptide-1 receptor agonist as an adjunct to standard care in adolescents with antipsychotic-associated obesity, defined as completion from baseline to end of treatment. The findings from this feasibility trial will inform the design and support the scale-up of a subsequent randomised controlled trial. The GOAL trial is a single-arm, open-label feasibility study conducted at Copenhagen University Hospital, Bispebjerg, Denmark, in collaboration with the Child and Adolescent Mental Health Center. A total of 34 adolescents aged 12-18 years with obesity, defined as body mass index SD score equal to or greater than +1.28 and body fat percentage at or above the 95th percentile, receiving stable antipsychotic treatment will be enrolled. The study population includes adolescents with a range of psychiatric diagnoses requiring antipsychotic treatment, including psychotic disorders, mood disorders and neurodevelopmental disorders. Adolescents receiving antipsychotic treatment under coercion are excluded. Participants will receive once-weekly subcutaneous semaglutide at a dose up to 2.4 milligrams for 36 weeks in addition to standard care, followed by an 18-month observational follow-up period. The primary outcome is study completion rate. Additional feasibility outcomes include recruitment rate, treatment adherence and completion of study procedures. Secondary outcomes include changes in body mass index SD score, body composition, metabolic biomarkers and psychiatric outcomes. Feasibility outcomes will be analysed descriptively. Exploratory longitudinal analyses will be conducted using linear mixed-effects models. The study complies with the Declaration of Helsinki and European Union Clinical Trials Regulation (536/2014) and is approved in the Clinical Trials Information System (2024-5 17 471-21-02). Written informed consent will be obtained from participants and their legal guardians. Results will be disseminated through peer-reviewed publications and scientific conferences. 2024-5 17 471-21-02.

Exit Interviews Examining Patient Experiences with Tirzepatide and Dulaglutide for Treatment of Type 2 Diabetes in the SURPASS-CVOT Trial.

In a clinical study, exit interview results indicate that self-reported treatment benefits were important to people who received long-term treatment with dulaglutide or tirzepatide. The purpose of this exit interview study was to examine the impact of long-term treatment with dulaglutide and tirzepatide from the perspective of patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease.

Stewart KD, Matza LS, Chinthammit C, Pavo I, Bartee AK, Boye KS

Qualitative exit interviews with people who recently completed a clinical trial can provide in-depth insights into their treatment experience and the benefits they consider most meaningful. The purpose of this exit interview study was to examine the impact of long-term treatment with dulaglutide and tirzepatide from the perspective of patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease. Interviews were conducted after participants completed treatment with either dulaglutide or tirzepatide in the multiyear SURPASS-CVOT clinical trial. Interviews were conducted by telephone or web-based conference using a semi-structured interview guide. The interviews were transcribed and analyzed following a content analysis approach. In total, 147 people were invited to participate in exit interviews across 10 US trial sites. A total of 74 participants were interviewed (63.5% male; mean age = 68.9 years), including 31 treated with dulaglutide and 43 treated with tirzepatide. Participants reported treatment benefits during the trial, such as improved glycemic control (97.3%), weight reduction (91.9%), reduced appetite (78.4%), improved diet and eating habits (64.9%), increased energy (56.8%), and decreased desire for unhealthy food (41.9%). Some also noted improvement in conditions other than T2D, including joint pain/osteoarthritis (18.9%) and sleep apnea (8.1%). Nearly all participants said these treatment-related changes were meaningful. Participants described improvements in quality of life and daily activities associated with treatment. The most commonly reported adverse event was nausea (28.4%). Most participants said they would be very likely (77.0%) or likely (16.2%) to recommend their treatment to others. Exit interview results indicate that self-reported treatment benefits were important to people who received long-term treatment with dulaglutide or tirzepatide.

Comparative Cardiorenal Efficacy and Safety of Finerenone, SGLT2 Inhibitors, Semaglutide and Their Combination in Diabetic Kidney Disease.

In a combined analysis of multiple studies, the efficacy of finerenone-SGLT2i combination therapy requires further investigation.

Zhou Z, Fu L, Chen D, Yu P, Xu G, Wu Q, Wu T, Yang P

To compare the cardiorenal efficacy and safety of finerenone, sodium-glucose cotransporter 2 inhibitors (SGLT2i), semaglutide and finerenone-SGLT2i combination therapy in diabetic kidney disease (DKD). PubMed, Embase and CENTRAL were searched through July 9, 2026 for randomized trials involving adults with Type 2 diabetes and DKD. A frequentist network meta-analysis estimated risk ratios (RRs) with 95% confidence intervals (CIs) for cardiorenal and safety outcomes. Ten randomized datasets involving 37 923 participants were included. Compared with control, dapagliflozin, canagliflozin, finerenone and semaglutide reduced both cardiovascular composite events and composite kidney outcomes; sotagliflozin reduced cardiovascular composite events, and empagliflozin reduced composite kidney outcomes. SGLT2i showed the broadest overall pattern of benefit across cardiorenal outcomes. Dapagliflozin was associated with a lower risk of the composite kidney outcome than semaglutide (RR 0.71, 95% CI: 0.53-0.94), while most other efficacy comparisons between active monotherapies were not statistically significant. Finerenone increased hyperkalaemia (RR 2.03, 95% CI: 1.82-2.26) and treatment discontinuation due to adverse events (RR 1.18, 95% CI: 1.02-1.35). Finerenone plus empagliflozin was associated with a higher risk of hyperkalaemia than empagliflozin alone (RR 2.48, 95% CI: 1.22-5.06). SGLT2i showed the broadest cardiorenal benefits, while finerenone and semaglutide provided additional protection across selected outcomes. Finerenone increased hyperkalaemia and treatment discontinuation. The efficacy of finerenone-SGLT2i combination therapy requires further investigation.

Cathelicidin LL-37 inhibits angiogenesis and migration in gastric cancer via inhibition of NF-κB/IL-6 signaling.

In a mouse study, this work provides a rationale for considering LL-37 as a potential therapeutic candidate. Aimed to revealed the function and underlying mechanism of LL-37 in GC, with a focus on blood vessel growth and metastasis.

Luo H, Li S, Du H, Yang W, You L, Mao D

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, often diagnosed at advanced stages with limited therapeutic options. Cathelicidin LL-37, an antimicrobial peptide, has demonstrated context-dependent roles in cancer progression. This study aimed to elucidate the function and underlying mechanism of LL-37 in GC, with a focus on angiogenesis and metastasis. The effects of LL-37 were investigated in GC cell lines (HGC27, MKN74, AGS, HSC-39, NCI-N87) and mouse models. In vitro assays included the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, wound healing assay, Transwell assay, tube formation assay, enzyme-linked immunosorbent assay (ELISA), quantitative real-time polymerase chain reaction (RT-qPCR), western blot, immunofluorescence staining, and chromatin immunoprecipitation (ChIP). Metastasis and xenograft models were established in nude mice to assess the anti-tumor efficacy of LL-37 in vivo. LL-37 significantly suppressed the viability of multiple GC cell lines and downregulated the expression of interleukin-6 (IL-6) and vascular endothelial growth factor A (VEGFA). Functionally, LL-37 inhibited angiogenesis, migration, and invasion of GC cells, and attenuated transforming growth factor (TGF)-β-induced pro-metastatic effects. These inhibitory effects were reversed by IL-6 overexpression. Mechanistically, LL-37 inactivated the nuclear factor-κB (NF-κB) pathway, as evidenced by reduced p65 phosphorylation, impaired nuclear translocation, and decreased binding to the IL-6 promoter. The NF-κB inhibitor BAY 11-7082 mimicked the suppressive effects of LL-37. In vivo, LL-37 administration markedly reduced lung metastasis and decreased the levels of IL-6, VEGFA, and phospho-p65 in xenograft tumors. LL-37 inhibits angiogenesis, migration, and invasion in GC by suppressing the NF-κB/IL-6 signaling axis. This work provides a rationale for considering LL-37 as a potential therapeutic candidate.

New and emerging somatostatin therapies for neuroendocrine tumors: "what is in the pipeline".

In a research review, numerous recent studies firmly establish these conclusions, all of which are reviewed here; and they will likely be further supported by additional studies that are in progress and also cited here.

Lee L, Ito T, Jensen RT

Somatostatin receptors (SSTRs) have played a central role in all aspects of the management of neuroendocrine/endocrine neoplasms (NENs). This includes in diagnosis of NENs with the widespread use of radiolabeled SSTR ligands to localize both the primary tumor location and extent of the tumors, as well as confirm its NEN nature. In NEN management non-radiolabeled SSTR agonists are the first line for control of the hormone-excess state for most functional NENs (F-NENs) as well as for the initial cytotoxic treatment of advanced tumor growth, and more recently, the use of radiolabeled SSTR ligands for the treatment of more aggressive advanced disease, as well as the assessment of tumor location, tumor extent and response to therapies. While somatostatin analogs (SSTA) have been successful in all of the above areas, there is increasing need for improvement, because not all patients respond to existing SSTAs therapies, others become resistant with time to existing SSTA treatment, current imaging with radiolabeled SSTAs is negative in some patients and ease of use/availability of ligand can be a problem and lastly, newer groups of patients are being considered for possible SSTA treatment with newer SSTA related compounds. In this perspective, the authors briefly review recent advances which are resulting or may result in new and emerging SSTAs that show promise in future use in NEN patients. It includes identification of both new or promising non-radioactive SSTA (cold SSTA) and radiolabeled SSTAs which could replace existing SSTAs now currently used, as well as new protocols for the new/promising SSTAs, or for existing SSTAs. These new/promising SSTAs/ or new/promising uses of these SSTAs include both chemically completely new SSTAs; pharmacologically new in their actions such as nonpeptide in nature; antagonist rather than agonist; longer acting in duration; and oral rather than parenteral administration. For peptide receptor radionuclide therapy (PRRT)/ imaging with radiolabeled SSTAs new developments covered include new promising SSTAs coupled to beta-emitters, alpha emitters, administered with radio-sensitizing agents, and new, promising protocols for PRRT retreatment, personalized treatment, adjuvant treatment or treatment of pediatric patients. They also include combinations of new/promising/exiting SSTAs both radiolabeled for PRRT or non-radiolabeled for tumor cytotoxic /and/or inhibitory effects formed by administration of the SSTA with other cytotoxic agents such as mTor inhibitors, chemotherapeutic agents, Tyrosine Kinase Inhibitors (TKIs), angiogenesis inhibitors, nonradioactive-SSTAs with PRRT or with immune therapy. This review of new and promising SSTR therapies involving both radiolabeled and non-radiolabeled for the future treatment of NENs strongly supports the conclusion that in the future SSTR- based drugs will continue to play prominent roles in all aspects of the management of NENs. This conclusion extends to the use of SST ligands to image these tumors to establish the location of the primary, location and extent of metastatic disease and the presence of SSTRs on the tumor for possible PRRT therapy; to the control of hormonal symptoms in F-NENs such as the carcinoid syndrome, vasoactive-intestinal-peptide- secreting (VIPomas)/ Adrenocortotropin-secreting(ACTHomas), etc. and to anti-proliferative roles for the treatment of advanced disease with both non-radioactive SSTAs, as well with PRRT with radiolabeled SSTAs and likely with novel new non-radiolabeled cytotoxic SSTAs. Numerous recent studies firmly establish these conclusions, all of which are reviewed here; and they will likely be further supported by additional studies that are in progress and also cited here.

Association between whole-blood NAD+ concentration and frailty in community-dwelling older adults: the Itabashi Longitudinal Study on Aging.

This study found further studies using cell- and tissue-specific measurements are needed to clarify the relationship between NAD⁺ metabolism and frailty. Examined the association of whole-blood NAD⁺ concentration with frailty in community-dwelling older adults.

Shida T, Hatanaka S, Kojima N, Osuka Y, Sasai H

Nicotinamide adenine dinucleotide (NAD⁺) is central to energy metabolism, redox reactions, and cellular signaling. However, human evidence linking circulating NAD⁺ concentrations to frailty remains limited. We examined the association of whole-blood NAD⁺ concentration with frailty in community-dwelling older adults. This cross-sectional analysis included community-dwelling adults aged ≥ 65 years from the 2025 Itabashi Longitudinal Study on Aging. Frailty was assessed using the revised Japanese Cardiovascular Health Study Criteria. Multivariable linear and logistic regression models adjusted for age, sex, and fasting time assessed the association. Restricted cubic spline, Firth penalized-likelihood logistic regression, and hematological sensitivity analyses were also performed. Among 529 participants (54.3% women), 32 (6.0%) had frailty. Median whole-blood NAD⁺ concentration was lower among participants with frailty than among those without frailty (24.00 vs. 25.00 µmol/L; P = 0.007). After adjustment for age, sex, and fasting time, higher whole-blood NAD⁺ concentration was associated with lower odds of frailty (OR per 1 µmol/L increase, 0.871; 95% CI, 0.780-0.970; P = 0.013). Restricted cubic spline analysis showed no clear evidence of nonlinearity. The association persisted after broader covariate adjustment using the Firth regression (OR, 0.880; 95% CI, 0.782-0.986) but was attenuated after additional adjustment for hematocrit (OR, 0.911; 95% CI, 0.800-1.034). Lower whole-blood NAD⁺ concentration was associated with frailty in community-dwelling older adults. Attenuation after hematocrit adjustment suggests that blood cell composition may partly explain this association. Further studies using cell- and tissue-specific measurements are needed to clarify the relationship between NAD⁺ metabolism and frailty.