Peptide Diabetes Research

Impact of changes in conventional risk factors induced by once-weekly GLP-1 receptor agonist exenatide on cardiovascular outcomes: an EXSCEL post hoc analysis.

Coleman, Ruth L · 2025

Using a validated diabetes outcomes model and participant-level data from EXSCEL, the researchers simulated how much of exenatide's cardiovascular benefits should result from its improvements in HbA1c, blood pressure, heart rate, LDL cholesterol, triglycerides, and weight. The model could only explain modest proportions of the observed benefits: 29% for MACE (major adverse cardiovascular events), 15% for all-cause mortality, 18% for cardiovascular death, and 29% for stroke.

Efficacy and Safety of Tirzepatide Compared with GLP-1 RAs in Patients with Type 2 Diabetes Treated with Basal Insulin: A Network Meta-analysis.

Osumili, Beatrice · 2025

Tirzepatide at all doses (5, 10, 15 mg) significantly outperformed GLP-1 RAs for both blood sugar control and weight loss when combined with basal insulin..

Influence of Type 2 Diabetes on the Effects of Tirzepatide in Patients With Heart Failure and a Preserved Ejection Fraction With Obesity: A Prespecified Stratification-Based Analysis.

Packer, Milton · 2025

Tirzepatide benefits for heart failure were consistent regardless of diabetes status: HR 0.64 with diabetes vs.

Tirzepatide: A Review in Type 2 Diabetes.

France, Nicole L · 2024

Tirzepatide (Mounjaro), the first dual GIP/GLP-1 receptor agonist, demonstrated superiority over multiple established diabetes treatments in the phase III SURPASS clinical trial program.

Effects of Semaglutide on Heart Failure Outcomes in Diabetes and Chronic Kidney Disease in the FLOW Trial.

Pratley, Richard E · 2024

Semaglutide reduced the composite outcome of heart failure events or cardiovascular death (HR 0.73, meaning a 27% reduction, p = 0.0005).

Evaluating remission of type 2 diabetes using a metabolic intervention including fixed-ratio insulin degludec and liraglutide: A randomized controlled trial.

Punthakee, Zubin · 2024

During the 16-week intervention, participants achieved significantly lower HbA1c (40 vs 51 mmol/mol, p < 0.0001) and lost more weight (3.3% vs 1.9%, p = 0.02) compared to controls. After stopping all glucose-lowering drugs, there was a 37% lower hazard of diabetes relapse in the intervention group (HR 0.63, 95% CI 0.45-0.88, p = 0.007).

Efficacy and safety of once-weekly tirzepatide for weight management compared to placebo: An updated systematic review and meta-analysis including the latest SURMOUNT-2 trial.

Qin, Wenhui · 2024

Weight loss was dose-dependent and significant at all three dose levels compared to placebo: - 5 mg: -8.07% body weight (about 7.5 kg lost) - 10 mg: -10.79% body weight (about 11 kg lost) - 15 mg: -11.83% body weight (about 11.5 kg lost) All three doses also reduced BMI and waist circumference.

Tirzepatide: unveiling a new dawn in dual-targeted diabetes and obesity management.

Rabbani, Syed Arman · 2024

Tirzepatide's dual mechanism activating both GIP and GLP-1 receptors produces superior efficacy compared to GLP-1-only drugs.

Evaluating the effectiveness and safety of various Tirzepatide dosages in the management of Type 2 diabetes mellitus: a network meta-analysis of randomized controlled trials.

Rangwala, Hussain Sohail · 2024

Compared to tirzepatide 5 mg: - 10 mg: additional 19% HbA1c reduction (MD: -0.19), additional 1.96 kg weight loss - 15 mg: additional 31% HbA1c reduction (MD: -0.32), additional 3.31 kg weight loss, and improved fasting glucose (MD: -6.71 mg/dL) The dose-response relationship was clear and consistent across the 10 studies.

GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2 Diabetes: Pleiotropic Cardiometabolic Effects and Add-on Value of a Combined Therapy.

Scheen, André J · 2024

GLP-1RAs primarily reduce atherosclerotic CV events (especially stroke) and renal outcomes, while SGLT2is reduce heart failure hospitalization and kidney disease progression.

Glycemia reduction in type 2 diabetes-Hypoglycemia outcomes: A randomized clinical trial.

Seaquist, Elizabeth R · 2024

Severe hypoglycemia rates: glargine 0.8%, glimepiride 1.3%, liraglutide 0.5%, sitagliptin 0.3% (p<0.05).

Superior metabolic improvement of polycystic ovary syndrome traits after GLP1-based multi-agonist therapy.

Sánchez-Garrido, Miguel A · 2024

GLP-1/Estrogen showed superior efficacy versus GLP-1/GIP, GLP-1/GIP/Glucagon, and metformin for metabolic complications of PCOS in mice.

Incretin-based therapy: a new horizon in diabetes management.

Zarei, Malek · 2024

Incretin-based therapies protect against diabetic complications across multiple organ systems: neuropathy, nephropathy, retinopathy, and cardiovascular disease, beyond their glucose-lowering effects..

Efficacy and Safety of Mazdutide in Chinese Patients With Type 2 Diabetes: A Randomized, Double-Blind, Placebo-Controlled Phase 2 Trial.

Zhang, Bo · 2024

Mazdutide 6 mg reduced HbA1c by 1.67% and body weight by 7.1% over 20 weeks, significantly exceeding both placebo and the reference GLP-1 drug dulaglutide on weight loss endpoints..

Time-Efficacy Relationship of Semaglutide in the Treatment of Type 2 Diabetes Mellitus: A Model-Based Meta-Analysis.

Zhang, Ke · 2024

Semaglutide 0.5 mg achieved Emax of -1.58% HbA1c reduction and 1 mg achieved -1.87%, with a rebound rate of 0.018 after peak efficacy.

Efficacy and Safety of Oral Semaglutide in the Treatment of Type 2 Diabetes: A Meta-Analysis.

Zhang, Lin · 2024

Oral semaglutide 14 mg reduced HbA1c by 1.08% vs placebo and 0.37% vs active comparators, with dose-dependent efficacy.

Efficacy and safety of adding once-weekly dulaglutide to basal insulin for inadequately controlled type 2 diabetes in Chinese patients (AWARD-CHN3): A randomized, double-blind, placebo-controlled, phase III trial.

Wang, Weimin · 2023

Adding once-weekly dulaglutide 1.5 mg to basal insulin glargine produced a 2.0% reduction in HbA1c from baseline at 28 weeks, compared to 1.1% with insulin glargine plus placebo — a highly significant difference of 1.0% (p<0.001).

Cardiorenal mechanisms of action of glucagon-like-peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors.

Cherney, David Z I · 2021

GLP-1 RAs and SGLT2i protect cardiovascular and renal systems through distinct but complementary mechanisms: GLP-1 RAs reduce atherosclerotic events while SGLT2i reduce heart failure and preserve kidney function..

Dipeptidyl peptidase-4 inhibitors, glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors for people with cardiovascular disease: a network meta-analysis.

Kanie, Takayoshi · 2021

GLP-1RA: reduced CV death (OR 0.87), all-cause death (OR 0.88), stroke (OR 0.87) — all high-certainty.

Efficacy and safety of the glucagon-like peptide-1 receptor agonist oral semaglutide in patients with type 2 diabetes mellitus: A systematic review and meta-analysis.

Li, Jingxin · 2021

Oral semaglutide vs placebo: reduced HbA1c, weight, FPG, SMPG, serious adverse events, and all-cause death.

Cardiovascular effects of glucagon-like peptide 1 receptor agonists: from mechanistic studies in humans to clinical outcomes.

Heuvelman, Valerie D · 2020

The review synthesizes preclinical and clinical evidence for cardiovascular effects of GLP-1 receptor agonists (GLP-1RAs): GLP-1 receptors are abundantly present in heart tissue, providing a direct mechanism for cardiac effects.

Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials.

Husain, Mansoor · 2020

Prior cardiovascular outcome trials showed semaglutide reduced MACE (major adverse cardiovascular events: CV death, non-fatal stroke, non-fatal MI) in high-risk patients.

Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk.

Husain, Mansoor · 2020

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.

Metabolic and cardiovascular benefits of GLP-1 agonists, besides the hypoglycemic effect (Review).

Iorga, Roua Anamaria · 2020

The review covers multiple GLP-1 receptor agonists and their non-glycemic benefits: Cardiovascular events: semaglutide and liraglutide demonstrated significant reduction in MACE with similar cardiovascular mortality rates.

Risk of Major Adverse Cardiovascular Events, Severe Hypoglycemia, and All-Cause Mortality for Widely Used Antihyperglycemic Dual and Triple Therapies for Type 2 Diabetes Management: A Cohort Study of All Danish Users.

Jensen, Morten Hasselstrøm · 2020

This massive real-world study compared outcomes across multiple diabetes drug combinations: Worst performer: metformin plus sulfonylurea (SU) had the highest risk of cardiovascular events and death.

The effect of glucagon-like peptide-1 receptor agonists liraglutide and semaglutide on cardiovascular and renal outcomes across baseline blood pressure categories: Analysis of the LEADER and SUSTAIN 6 trials.

Leiter, Lawrence A · 2020

No statistical heterogeneity in cardiovascular (MACE) or nephropathy outcomes across blood pressure categories for either liraglutide or semaglutide vs placebo..

Glycaemic and non-glycaemic efficacy of once-weekly GLP-1 receptor agonists in people with type 2 diabetes.

Patel, Dhiren · 2020

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..

Safety of injectable semaglutide for type 2 diabetes.

Peter, Rajesh · 2020

Semaglutide demonstrated cardiovascular superiority in SUSTAIN 6, with a safety profile typical of GLP-1RAs.

Incretin-based drugs and risk of lung cancer among individuals with type 2 diabetes.

Rouette, J · 2020

Neither DPP-4 inhibitors (HR 1.07, 95% CI 0.87-1.32) nor GLP-1 receptor agonists (HR 1.02, 95% CI 0.68-1.54) were associated with increased lung cancer risk, with no duration-response relationship..

Safety and tolerability of once-weekly GLP-1 receptor agonists in type 2 diabetes.

Trujillo, Jennifer · 2020

Once-weekly GLP-1 RAs have manageable safety profiles dominated by gastrointestinal side effects, with differences between agents that inform treatment selection..

Long-acting GLP-1 receptor agonists: Findings and implications of cardiovascular outcomes trials.

Urquhart, Scott · 2020

Long-acting GLP-1 RAs are cardiovascularly safe, with liraglutide, semaglutide, and dulaglutide demonstrating significant cardiovascular risk reduction in outcome trials..

Gut-brain axis: regulation of glucose metabolism.

Heijboer, A C · 2006

The gut-brain glucose regulatory axis operates through incretin peptides (GLP-1, GIP), neural signals, and other gut hormones to control glucose metabolism — pharmacological exploitation has produced GLP-1 agonists and DPP-4 inhibitors as major diabetes drug classes..

Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters.

le Roux, Carel W · 2006

Bariatric surgery produced comprehensive gut hormone profile transformation: elevated GLP-1, PYY3-36, and oxyntomodulin with suppressed ghrelin, creating an anorectic hormonal milieu that facilitates weight loss and improves glucose metabolism beyond mechanical restriction..

Trends in Utilization of Glucose- and Weight-Lowering Medications After Tirzepatide Approval in the United States : A Population-Based Cohort Study.

Ostrominski, John W · 2025

Tirzepatide reached 12.3% of diabetes medication dispensations and 40.6% of weight-loss medication dispensations within about 18 months of market entry..

Effectiveness for adding or switching from other incretin-related drugs to oral semaglutide in type 2 diabetes.

Oya, Junko · 2025

Oral semaglutide reduced HbA1c by 0.85% in naive patients, 0.67% in DPP-4i switchers, and 0.13% in GLP-1 RA switchers..

Real-World Analysis of Short-Term Effectiveness of Oral Semaglutide: Impact on Glycometabolic Control and Cardiovascular Risk.

Palazzi, Sara · 2025

Oral semaglutide produced significant short-term reductions in HbA1c and body weight, along with improvements in cardiovascular risk markers, in a real-world type 2 diabetes population..

Safety and efficacy of GLP-1/FGF21 dual agonist HEC88473 in MASLD and T2DM: A randomized, double-blind, placebo-controlled study.

Xiang, Lin · 2025

HEC88473, a GLP-1/FGF21 dual agonist given as weekly subcutaneous injections for 5 weeks, produced dose-proportional reductions in liver fat measured by MRI-PDFF.

Achievement of normoglycemia with tirzepatide in type 2 diabetes mellitus: A step closer to drug-induced diabetes remission?

Popovic, Djordje S · 2024

Tirzepatide did not just improve blood sugar control.

Tirzepatide use and the risk of cancer among individuals with type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

Popovic, Djordje S · 2024

Across all 9 trials, tirzepatide did not increase the risk of cancer overall or any specific cancer type.

Non-alcoholic fatty liver disease in type 2 diabetes: Emerging evidence of benefit of peroxisome proliferator-activated receptors agonists and incretin-based therapies.

Pramanik, Subhodip · 2024

PPAR agonists work by making cells more sensitive to insulin.

Antidiabetic Treatment and Prevention of Ischemic Stroke: A Systematic Review.

Prentza, Vasiliki · 2024

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.

SGLT2 Inhibitors, but Not GLP-1 Receptor Agonists, Reduce Incidence of Gout in People Living With Type 2 Diabetes Across the Therapeutic Spectrum.

Preston, Frank G · 2024

SGLT2 inhibitors with metformin reduced gout incidence by 25% compared to metformin alone (HR 0.75, p < 0.0001).

NOVEL AGENTS IN THE MANAGEMENT OF DIABETES AND RISK OF WORSENING DIABETIC RETINOPATHY.

Rajagopal, Rithwick · 2024

In the SUSTAIN-6 cardiovascular outcome trial, semaglutide was associated with approximately 75% increased risk of diabetic retinopathy (DR) worsening.

SPIRIT: Assessing Clinical Parameters Associated with Using IDegLira in Patients with Type 2 Diabetes in a Real-World Setting in Colombia.

Ramírez-Rincón, Alex · 2024

After approximately 26 weeks on IDegLira: - HbA1c decreased by 1.3% (from 9.1% to 7.8%, p < 0.0001) - Body weight decreased by 1 kg (from 76.1 to 75.1 kg, p < 0.0001) - No severe hypoglycemic events observed - Mean final IDegLira dose: 21.3 units These results were achieved in patients who had previously been on basal insulin (with or without oral diabetes drugs) and were not reaching their blood sugar targets.

Assessing the Renal Outcomes of Semaglutide in Diabetic Kidney Disease: A Systematic Review.

Rehman, Shuja Ur · 2024

Albuminuria was more consistently reduced by semaglutide than eGFR.

Transforming body composition with semaglutide in adults with obesity and type 2 diabetes mellitus.

Rodríguez Jiménez, Beatriz · 2024

Both oral and subcutaneous semaglutide significantly reduced fat mass and improved metabolic parameters in adults with obesity and type 2 diabetes over 24 weeks..

Harmine and exendin-4 combination therapy safely expands human β cell mass in vivo in a mouse xenograft system.

Rosselot, Carolina · 2024

Harmine plus exendin-4 combination therapy safely increased human beta cell mass in vivo in a mouse xenograft system without causing harmful proliferation..

Transforming Diabetes Care: The Molecular Pathways through Which GLP1-RAs Impact the Kidneys in Diabetic Kidney Disease.

Rroji, Merita · 2024

GLP-1 receptor agonists protect kidneys in diabetic kidney disease through anti-inflammatory, antioxidant, and anti-fibrotic molecular pathways, complementing existing kidney therapies..

Efficacy and safety of glucagon-like peptide-1 receptor agonists on prediabetes: a systematic review and meta-analysis of randomized controlled trials.

Salamah, Hazem Mohamed · 2024

GLP-1RAs significantly increased prediabetes reversion to normoglycemia (RR 1.76, 95% CI 1.45–2.13, p < 0.00001) and prevented new-onset diabetes (RR 0.28, 95% CI 0.19–0.43, p < 0.00001).

Evaluating the Impact of Novel Incretin Therapies on Cardiovascular Outcomes in Type 2 Diabetes: An Early Systematic Review.

Salmen, Teodor · 2024

Both tirzepatide and retatrutide improve glycemia, HbA1c, body weight, lipid profiles, blood pressure, and renal parameters in type 2 diabetes patients.

PIONEER REAL UK: A Multi-Centre, Prospective, Real-World Study of Once-Daily Oral Semaglutide Use in Adults with Type 2 Diabetes.

Saravanan, Ponnusamy · 2024

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.

Efficacy and Safety of Escalating the Dose of Oral Semaglutide from 7 to 14 mg: A Single-Center, Retrospective Observational Study.

Sato, Genki · 2024

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.

A randomized phase 2b trial examined the effects of the glucagon-like peptide-1 and glucagon receptor agonist cotadutide on kidney outcomes in patients with diabetic kidney disease.

Selvarajah, Viknesh · 2024

Cotadutide dose-dependently reduced UACR at week 14: 300 μg (-43.9%, CI -54.7 to -30.6) and 600 μg (-49.9%, CI -59.3 to -38.4) vs placebo.

Effects of GLP-1 Receptor Agonist on Glycolipid Metabolism and Micro Inflammatory Status in Patients with Abdominal Obesity and Type 2 Diabetes.

Shao, Wei · 2024

Liraglutide added to metformin significantly improved SBP, DBP, BMI, waist-hip ratio, glycolipid metabolism indices, and microinflammatory markers compared to metformin alone over 12 weeks (P<0.05).

Efficacy and safety of switching from a dipeptidyl peptidase-4 inhibitor to oral semaglutide in Japanese patients with type 2 diabetes mellitus.

Yoneda, Chihiro · 2024

Switching from DPP-4i to oral semaglutide reduced mean HbA1c from 7.8% to 7.0% (P significant) and decreased body weight (P significant).

Cow's Milk Bioactive Molecules in the Regulation of Glucose Homeostasis in Human and Animal Studies.

Yuzbashian, Emad · 2024

Milk-derived bioactive peptides from whey and casein regulate glucose homeostasis through insulinotropic effects, incretin hormone modulation, and RAAS inhibition, supporting dairy consumption as potentially protective against metabolic disorders..

Benchmarking the medication efficiency and technological progress of diabetes drugs.

Zhang, Hongwei · 2024

Oral semaglutide, subcutaneous semaglutide, and dulaglutide achieved the highest medication efficiency scores among 20 T2D drugs, while lixisenatide and liraglutide scored lower despite being in the same GLP-1 class..

Predicting responsiveness to GLP-1 pathway drugs using real-world data.

Zhu, Xiaodong · 2024

Machine learning models using real-world data successfully predicted individual patient responsiveness to GLP-1 pathway drugs, enabling more targeted treatment selection..

Effects of GLP-1 Receptor Agonists on Bone Mineral Density in Patients with Type 2 Diabetes Mellitus: A 52-Week Clinical Study.

Cai, Ting-Ting · 2021

GLP-1 RAs increased bone mineral density at multiple skeletal sites over 52 weeks, while placebo showed significant bone loss at the spine, femoral neck, and total hip..

Therapeutic Potential of Peptides Derived from Animal Venoms: Current Views and Emerging Drugs for Diabetes.

Coulter-Parkhill, Aimee · 2021

Venom-derived peptides from diverse species (bees, cone snails, sea anemones, scorpions, snakes, spiders) show potential for glycemic control, building on the proven success of exendin-4/exenatide..

Anticipatory guidance and systematic review of prescribing combination incretin therapy in the treatment of type 2 diabetes.

Cowart, Kevin · 2021

Combining GLP-1 RA and DPP-4 inhibitor provides only a small incremental reduction in HbA1c and weight loss, with the benefit unlikely to offset potential pancreatitis risk and additional cost..

Prescribing in Type 2 Diabetes Patients With and Without Cardiovascular Disease History: A Descriptive Analysis in the UK CPRD.

Farmer, Ruth E · 2021

GLP-1RA use was only 4.3-4.9% and SGLT2i use 9.8-13.8% in UK T2DM patients by December 2019, with paradoxically lower use in patients with CVD history who would benefit most.

Asthma Exacerbations in Patients with Type 2 Diabetes and Asthma on Glucagon-like Peptide-1 Receptor Agonists.

Foer, Dinah · 2021

GLP-1RA users had significantly fewer asthma exacerbations at 6 months compared to SGLT-2 inhibitors (IRR 2.98), DPP-4 inhibitors (IRR 2.45), sulfonylureas (IRR 1.83), and basal insulin (IRR 2.58), all with p<0.05..

GLP-2 Is Locally Produced From Human Islets and Balances Inflammation Through an Inter-Islet-Immune Cell Crosstalk.

He, Wei · 2021

Human islets actively secrete GLP-2 under normal conditions, and this secretion increases under diabetic stress conditions (high glucose/palmitate, inflammatory cytokines, and LPS).

The role of central corticotrophin-releasing factor receptor signalling in plasma glucose maintenance through ghrelin secretion in calorie-restricted mice.

Kimura, Risa · 2021

Central CRF-R signaling → sympathetic activation → ghrelin secretion → plasma glucose maintenance during 60% calorie restriction.

Macronutrient intake, appetite, food preferences and exocrine pancreas function after treatment with short- and long-acting glucagon-like peptide-1 receptor agonists in type 2 diabetes.

Quast, Daniel R · 2021

Both GLP-1 receptor agonists produced comparable effects on: - Macronutrient and energy intake (equally reduced) - Body weight loss - Appetite reduction The key mechanistic finding was that weight loss and appetite reduction were NOT related to delayed gastric emptying or GI side effects (p > 0.05 for both).

Adiponectin treatment improves insulin resistance in mice by regulating the expression of the mitochondrial-derived peptide MOTS-c and its response to exercise via APPL1-SIRT1-PGC-1α.

Guo, Qi · 2020

In mice lacking the adiponectin gene (Adipoq-/- knockouts), MOTS-c levels in blood and muscle were significantly lower than normal.

Oral semaglutide versus injectable glucagon-like peptide-1 receptor agonists: a cost of control analysis.

Hansen, B B · 2020

The cost-of-control analysis compared oral semaglutide 14 mg against six injectable GLP-1 receptor agonists for type 2 diabetes.

A Relative Cost of Control Analysis of Once-Weekly Semaglutide Versus Exenatide Extended-Release, Dulaglutide and Liraglutide in the UK.

Johansen, Pierre · 2020

Annual per-patient costs were similar across all four GLP-1 receptor agonists in the UK market.

Incretin combination therapy for the treatment of non-alcoholic steatohepatitis.

Kannt, Aimo · 2020

Mice were fed a high-fat, high-fructose, high-cholesterol diet for 36 weeks to develop NASH with fibrosis, then treated for 8 weeks.

Mitochondrial-derived peptides in energy metabolism.

Merry, Troy L · 2020

Mitochondrial-derived peptides serve as retrograde metabolic signals — declining in metabolic disease but rising during adaptive stress responses like exercise — and can improve insulin sensitivity when administered therapeutically..

Effectiveness of dulaglutide vs liraglutide and exenatide once-weekly. A real-world study and meta-analysis of observational studies.

Morieri, Mario Luca · 2020

Dulaglutide reduced HbA1c 0.24% more than liraglutide in real-world clinical practice (p=0.003), confirmed by meta-analysis of observational studies..

Nephroprotective effects of GLP-1 receptor agonists: where do we stand?

Mosterd, Charlotte M · 2020

GLP-1 receptor agonists reduce macro-albuminuria in cardiovascular safety trials, with multiple proposed kidney-protective mechanisms including anti-inflammatory, hemodynamic, and metabolic effects..

Amylin and pramlintide modulate γ-secretase level and APP processing in lipid rafts.

Mousa, Youssef M · 2020

Amylin and pramlintide increased amyloid-beta production by modulating APP and γ-secretase in lipid rafts, leading to increased Aβ burden, synaptic loss, and neuroinflammation in TgSwDI Alzheimer's mice..

Acyl-ghrelin Is Permissive for the Normal Counterregulatory Response to Insulin-Induced Hypoglycemia.

Shankar, Kripa · 2020

Ghrelin knockout mice showed impaired counterregulatory responses to insulin-induced hypoglycemia, demonstrating that acyl-ghrelin is permissive for normal blood sugar recovery during hypoglycemic episodes..

Liraglutide improves memory in obese patients with prediabetes or early type 2 diabetes: a randomized, controlled study.

Vadini, Francesco · 2020

Liraglutide improved cognitive function in the memory domain in obese patients with prediabetes or early T2D, independent of weight loss effects..

Novel strategies in the oral delivery of antidiabetic peptide drugs - Insulin, GLP 1 and its analogs.

Ismail, Ruba · 2017

The review evaluated multiple strategies for oral delivery of antidiabetic peptides (insulin, GLP-1, and GLP-1 analogs), identifying two main barriers that must be overcome: degradation by proteolytic enzymes in the gastrointestinal tract and poor absorption through the intestinal wall. Among all approaches reviewed — including absorption enhancers, enzyme inhibitors, chemical modifications, and various carrier systems — nanocarrier systems emerged as the most promising platform.

Hormone-based therapies in the regulation of fuel metabolism and body weight.

Kesty, Nicole C · 2008

Hormone-based fuel metabolism drugs span GLP-1 agonists (semaglutide class), amylin analogs (pramlintide), PYY analogs, and ghrelin modulators for integrated obesity/diabetes treatment — exploiting endogenous regulatory peptide systems for superior metabolic control..

New drugs for type 2 diabetes mellitus: what is their place in therapy?

Krentz, Andrew J · 2008

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..

Combination pharmacotherapy with incretins: what works best and when?

Over, Rebecca K · 2008

GLP-1 agonists and DPP-4 inhibitors combine synergistically with metformin (first-line), sulfonylureas, thiazolidinediones, and insulin for T2DM, with combination selection guided by patient weight, hypo risk, and HbA1c target — practical combination pharmacotherapy guidance..

Managed care perspective on three new agents for type 2 diabetes.

VanDeKoppel, Shawna · 2008

Managed care analysis of exenatide (GLP-1 agonist: weight loss, injectable), sitagliptin (DPP-4 inhibitor: oral, weight neutral), and pramlintide (amylin analog: injectable, weight loss) for T2DM positioning — incretin drugs transforming diabetes pharmacotherapy economics..

New therapies for diabetes.

Green, Dina E · 2007

GLP-1 receptor agonists and DPP-4 inhibitors exploit the incretin system for diabetes treatment, providing glucose-dependent insulin stimulation, weight loss (GLP-1 agonists), and low hypoglycemia risk — the most significant new diabetes drug class..

Quinazolinone derivatives as orally available ghrelin receptor antagonists for the treatment of diabetes and obesity.

Rudolph, Joachim · 2007

Quinazolinone ghrelin receptor antagonists showed oral bioavailability, reduced food intake, and improved glucose tolerance in animal models — positioning orally active ghrelin blockade as a dual-mechanism drug approach for treating both diabetes and obesity simultaneously..

Mitochondrial targeting with antioxidant peptide SS-31 prevents mitochondrial depolarization, reduces islet cell apoptosis, increases islet cell yield, and improves posttransplantation function.

Thomas, Dolca A · 2007

SS-31 (mitochondria-targeted peptide) prevented mitochondrial depolarization and apoptosis in pancreatic islet cells, preserved glucose-stimulated insulin secretion, and improved glycemic control in diabetic animals — protecting the beta-cells that diabetes progressively destroys..

Inhaled insulin (Exubera): Combining efficacy and convenience.

Bellary, Srikanth · 2006

Exubera was approved in 2006 as the first inhaled insulin and the first peptide hormone successfully delivered via the pulmonary route for clinical use.

Ghrelin differentially affects hepatic and peripheral insulin sensitivity in mice.

Heijboer, A C · 2006

Ghrelin reduced hepatic insulin sensitivity (increased gluconeogenesis) while showing different effects on peripheral insulin sensitivity in mice, demonstrating tissue-specific ghrelin-insulin interactions with implications for diabetes pathophysiology..

The occurrence and receptor specificity of endogenous opioid peptides within the pancreas and liver of the rat. Comparison with brain.

Khawaja, X Z · 1990

Pancreas and liver contain substantial opioid peptide levels exceeding brain content, with functional delta and kappa receptors on pancreatic islets.

Fatty Pancreas: Its Potential as a Risk Factor for Pancreatic Cancer and Clinical Implications.

Otsuka, Nao · 2025

Fatty pancreas may be linked to increased risk of pancreatic ductal adenocarcinoma through chronic inflammation and lipotoxicity, and certain diabetes drugs might help..

GLP-1R Agonists Improve Ocular Surface Parameters in Type 2 Diabetes Mellitus.

Ottonelli, Giovanni · 2025

GLP-1 RA users had median Schirmer values of 15 mm vs.

The comparison of the antidiabetic effects of exenatide, empagliflozin, quercetin, and combination of the drugs in type 2 diabetic rats.

Korkmaz, Yasemin · 2024

In type 2 diabetic rats, the GLP-1 agonist exenatide showed more pronounced antidiabetic effects than either empagliflozin (an SGLT2 inhibitor) or quercetin (a plant flavonoid) when used alone.

Semaglutide and smoking cessation in individuals with type 2 diabetes mellitus: there is no smoke without fire!

Popovic, Djordje S · 2024

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.

Sodium-glucose cotransporter-2 inhibitor (SGLT2i) plus glucagon-like peptide type 1 receptor combination is more effective than SGLT2i plus dipeptidyl peptidase-4 inhibitor combination in treating obese mice metabolic dysfunction-associated steatotic liver disease (MASLD).

Reis-Barbosa, Pedro H · 2024

High-fat diet versus control: liver triglycerides increased 82%, steatosis increased 850%, glucose intolerance increased 71%, insulin increased 98%, and insulin resistance increased 68%. Both drug combinations improved all parameters compared to untreated obese mice: - Empagliflozin + linagliptin: glucose intolerance -60%, insulin -61%, insulin resistance -46%, TAG -61%, steatosis -58% - Empagliflozin + dulaglutide: glucose intolerance -71%, insulin -58%, insulin resistance -62%, TAG -61%, steatosis -82% Principal component analysis clearly separated the groups: the GLP-1 combination was furthest from the disease group, while the DPP-4 combination fell between control and the GLP-1 group..

The dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist tirzepatide effects on body weight evolution, adiponectin, insulin and leptin levels in the combination of obesity, type 2 diabetes and menopause in mice.

Reis-Barbosa, Pedro H · 2024

The triple-challenge model (obesity + diabetes + ovariectomy) created the most severe metabolic dysfunction.

The adipose tissue melanocortin 3 receptor is targeted by ghrelin and leptin and may be a therapeutic target in obesity.

Rosendo-Silva, Daniela · 2024

The melanocortin 3 receptor in adipose tissue is regulated by ghrelin and leptin, and its disruption in obesity suggests it could be a therapeutic target for metabolic disease..

GLP-1 receptor agonist improves metabolic disease in a pre-clinical model of lipodystrophy.

Roumane, Ahlima · 2024

A GLP-1 receptor agonist improved glucose intolerance, insulin resistance, and metabolic disease in lipodystrophic mice, even in the near-complete absence of adipose tissue..

Dual effects of dulaglutide on glycemic control and knee osteoarthritis pain in elderly patients with Type 2 diabetes.

Samajdar, Shambo Samrat · 2024

HbA1c decreased from 8.7% to 6.5% over 6 months.

Effects of the switch from dulaglutide to tirzepatide on glycemic control, body weight, and fatty liver: a retrospective study.

Sawamura, Toshitaka · 2024

Switching from dulaglutide to tirzepatide produced average reductions of 1.2% in HbA1c and 3.6 kg in body weight at 6 months.

GLP-1 receptor agonist attenuates tubular cell ferroptosis in diabetes via enhancing AMPK-fatty acid metabolism pathway through macropinocytosis.

Shen, Rui · 2024

Exendin-4 suppressed ferroptosis in diabetic kidney tubular cells by activating AMPK-fatty acid metabolism signaling, reducing iron overload and lipid peroxidation through macropinocytosis-dependent cellular uptake..

Liraglutide ameliorates high glucose-induced vascular endothelial injury through TRIB3/NF-κB signaling pathway.

Shi, Lili · 2024

Liraglutide protected endothelial cells from high glucose-induced apoptosis, oxidative stress, inflammasome activation, and pyroptosis by regulating the TRIB3/NF-κB/IκB-α signaling pathway..

GLP-1 receptor agonist-induced diabetic ketoacidosis: A case report.

Zhang, Jiaming · 2024

A patient misdiagnosed as type 2 diabetes developed severe DKA within 24 hours of starting dulaglutide and discontinuing insulin, leading to her correct diagnosis of LADA..

Novel enzyme-resistant pancreatic polypeptide analogs evoke pancreatic beta-cell rest, enhance islet cell turnover, and inhibit food intake in mice.

Zhu, Wuyun · 2024

Novel enzyme-resistant pancreatic polypeptide analogs promoted pancreatic beta cell proliferation, offering a potential peptide-based approach to restoring insulin-producing cell mass..

Development of High Affinity Calcitonin Analog Fragments Targeting Extracellular Domains of Calcitonin Family Receptors.

Lee, Sangmin · 2021

Three mutations (N26D, S29P, P32HYP) in sCT(22-32) increased CTR ECD affinity 21-fold.

The effect of the ghrelin-receptor agonist capromorelin on glucose metabolism in healthy cats.

Pires, J · 2021

Capromorelin activates the ghrelin receptor (GHSR), which is found on pancreatic delta cells that produce somatostatin.

Identification of novel DPP-IV inhibitory peptides from Atlantic salmon (Salmo salar) skin.

Jin, Ritian · 2020

Salmon skin collagen was broken down by four different enzymes.

The protective effects of dulaglutide against advanced glycation end products (AGEs)-induced degradation of type Ⅱ collagen and aggrecan in human SW1353 chondrocytes.

Li, Hai · 2020

Dulaglutide protected chondrocytes from AGE-induced cartilage matrix degradation by reducing MMP-3/13, ADAMTS-4/5, inflammatory cytokines, and ROS via NF-κB pathway inhibition..

Targeting NF-κB by the Cell-Permeable NEMO-Binding Domain Peptide Improves Albuminuria and Renal Lesions in an Experimental Model of Type 2 Diabetic Nephropathy.

Opazo-Ríos, Lucas · 2020

Active NBD peptide reduced albuminuria by >40%, decreased podocyte loss and basement membrane thickness, and modulated inflammatory markers in a type 2 diabetic nephropathy mouse model..

Transplantation of Endothelial Progenitor Cells in Obese Diabetic Rats Following Myocardial Infarction: Role of Thymosin Beta-4.

Poh, Kian Keong · 2020

Tβ4 at 10 ng/mL improved diabetic EPC migration, tubule formation, and angiogenic factor secretion in vitro, and increased capillary density in vivo, but only non-Tβ4-treated EPCs significantly improved left ventricular ejection fraction..

Host Defense Peptide RNase 7 Is Down-regulated in the Skin of Diabetic Patients with or without Chronic Ulcers, and its Expression is Altered with Metformin.

Rodríguez-Carlos, Adrian · 2020

RNase 7 was significantly decreased in skin of diabetic patients with and without foot ulcers compared to healthy donors.

A once-monthly GLP-1 receptor agonist for treatment of diabetic cats.

Schneider, E L · 2020

A hydrogel microsphere delivery system with a self-cleaving β-eliminative linker enables sustained release of exenatide from a single subcutaneous injection, providing once-monthly dosing for feline diabetes treatment..

[D-Leu-4]-OB3, a synthetic peptide amide with leptin-like activity, augments the effects of orally delivered exenatide and pramlintide acetate on energy balance and glycemic control in insulin-resistant male C57BLK/6-m db/db mice.

Leinung, Matthew C · 2012

Co-administration of [D-Leu-4]-OB3, a synthetic leptin-like peptide, with exenatide resulted in mice that were 4.2% lighter than their starting weight after 14 days — a stark contrast to the 19.7% weight gain in control mice and the 13.9% gain with exenatide alone. For blood glucose, co-delivery of [D-Leu-4]-OB3 with exenatide reduced levels by 38.3% (vs.

Gastric motor effects of ghrelin and growth hormone releasing peptide 6 in diabetic mice with gastroparesis.

Qiu, Wen-Cai · 2008

Ghrelin and GHRP-6 restored gastric contractile activity and emptying in diabetic gastroparesis mice, with effects mediated through smooth muscle and neural pathways — confirming GH secretagogues as gastroprokinetic agents for diabetic GI dysfunction..

Therapeutic effects of ghrelin and growth hormone releasing peptide 6 on gastroparesis in streptozotocin-induced diabetic guinea pigs in vivo and in vitro.

Qiu, Wen-cai · 2008

Ghrelin and GHRP-6 restored gastric emptying in streptozotocin-diabetic rats with gastroparesis, improving gastric motility through GHS-R activation — validating GH secretagogues as therapeutic agents for diabetic gastroparesis, a common and debilitating complication..

STZ-induced diabetes decreases and insulin normalizes POMC mRNA in arcuate nucleus and pituitary in rats.

Kim, E M · 1999

STZ-induced diabetes decreased POMC mRNA by significant amounts in the hypothalamic arcuate nucleus and anterior pituitary by 2-4 weeks, with insulin treatment (3 weeks) normalizing expression levels..

Pentadecapeptide BPC 157 attenuates gastric lesions induced by alloxan in rats and mice.

Petek, M · 1999

BPC-157 significantly attenuated alloxan-induced gastric lesions in rats (200 mg/kg SC) and mice (400 mg/kg IP), reducing lesion severity and accelerating healing over the observation period..

Glucose stimulation of pancreatic beta-cell lines induces expression and secretion of dynorphin.

Josefsen, K · 1998

Glucose stimulation induced prodynorphin gene expression in pancreatic beta-cell lines, with dynorphin peptides being processed and secreted, suggesting a novel opioid-mediated feedback mechanism in glucose regulation..

Autoradiographic localization of beta-endorphin binding in the pancreas.

Zhang, M · 1994

Specific beta-endorphin binding sites were localized to pancreatic islet cells, blocked by mu and delta receptor ligands, confirming opioid receptors on insulin-producing cells..

Immunohistochemistry of opioid peptides in the guinea pig endocrine pancreas.

Cetin, Y · 1990

All three opioid peptide families are present in the guinea pig endocrine pancreas but in different cell types, with processing pathways distinct from other organs..

Effects of beta-endorphin, met-enkephalin, and dynorphin A on basal and stimulated insulin secretion in the mouse.

Ahrén, B · 1989

Beta-endorphin had a dose-dependent biphasic effect on insulin secretion.

Lidocaine treatment of painful diabetic neuropathy and endogenous opioid peptides in plasma.

Kastrup, J · 1989

Lidocaine increased plasma beta-endorphin equally in patients and controls, but pain relief in diabetic neuropathy was not correlated with beta-endorphin changes..

Endogenous opiates do not influence glucose and lipid metabolism in rat adipocytes.

Hauner, H · 1988

Six opioid-related substances were tested on isolated rat adipocytes (fat cells): - Beta-endorphin, dynorphin, met-enkephalin, leu-enkephalin, and morphine (agonists) - Naloxone (antagonist) None altered insulin binding to fat cells.

Strategies for the delivery of antidiabetic drugs via intranasal route.

Dholakia, Jheel · 2021

Intranasal delivery of insulin and glucagon-like peptides demonstrates improved therapeutic levels and patient compliance, with drugs transported through epithelial tight junctions via the paracellular route..

Mitochondrial dysfunction and beneficial effects of mitochondria-targeted small peptide SS-31 in Diabetes Mellitus and Alzheimer's disease.

Ding, Xiao-Wen · 2021

SS-31 peptide targets mitochondria directly, inhibiting oxidative stress and restoring mitochondrial function with greater therapeutic potential than traditional antioxidants like vitamin E in models of diabetes and Alzheimer's disease..

Comparative efficacy of 5 sodium glucose cotransporter 2 inhibitor and 7 glucagon-like peptide 1 receptor agonists interventions on cardiorenal outcomes in type 2 diabetes patients: A network meta-analysis based on cardiovascular or renal outcome trials.

Duan, Xue-Yan · 2021

Sotagliflozin ranked first for MACE (HR 0.76), heart failure hospitalization (HR 0.59), MI (HR 0.65), and stroke (HR 0.56).

Efficacy and safety of novel twincretin tirzepatide a dual GIP and GLP-1 receptor agonist in the management of type-2 diabetes: A Cochrane meta-analysis.

Dutta, Deep · 2021

Tirzepatide reduced HbA1c by an additional 0.75%, weight by 8.63 kg, BMI by 1.80 kg/m², and waist circumference by 4.43 cm versus active comparators.

Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes.

Frías, Juan P · 2021

Tirzepatide was noninferior and superior to semaglutide 1mg: HbA1c reductions of -2.01%, -2.24%, -2.30% (5/10/15mg) vs -1.86% semaglutide.

Effects of oral semaglutide on energy intake, food preference, appetite, control of eating and body weight in subjects with type 2 diabetes.

Gibbons, Catherine · 2021

Oral semaglutide 14mg reduced total daily ad libitum energy intake by 38.9% versus placebo (treatment difference -5,096 kJ, p=0.0001).

Impact of dietary intake of resistant starch on obesity and associated metabolic profiles in human: a systematic review of the literature.

Guo, Jiayue · 2021

RS intake significantly improved GLP-1 and PYY gut hormone levels, improved blood glucose (5/8 studies) and insulin sensitivity (2/3 studies).

High Coexpression of the Ghrelin and LEAP2 Receptor GHSR With Pancreatic Polypeptide in Mouse and Human Islets.

Gupta, Deepali · 2021

In mice, 85% of GHSR-expressing islet cells coexpress PP and 50% coexpress SST.

Effect of combined therapy of mesenchymal stem cells with GLP-1 receptor agonist, exenatide, on early-onset nephropathy induced in diabetic rats.

Habib, Heba A · 2021

Combined ADMSC + exenatide therapy showed superior renoprotective effects versus ADMSCs alone in diabetic rats, with significant improvement in kidney function and reduced inflammatory, fibrotic, and apoptotic markers..

Identification and Metabolic Profiling of a Novel Human Gut-derived LEAP2 Fragment.

Hagemann, Christoffer A · 2021

RYGB upregulated LEAP2 expression.

Management of post-transplant diabetes: immunosuppression, early prevention, and novel antidiabetics.

Hecking, Manfred · 2021

Retrospective data suggest GLP-1RAs are safe in PTDM with no major concerns, particularly suitable for obese transplant recipients.

Role of Glucagon-Like Peptide-1 (GLP-1) Receptor Agonists in Hypoglycemia.

Ja'arah, Daria · 2021

GLP-1 receptor agonists were proposed to cause hypoglycemia in healthy normoglycemic subjects, challenging the assumption of purely glucose-dependent action.

Cell-Penetrating Peptides as a Potential Drug Delivery System for Effective Treatment of Diabetes.

Korivi, Mallikarjuna · 2021

CPPs enhance diabetes treatment by: (1) improving hypoglycemic drug effectiveness, (2) facilitating insulin delivery, (3) synergizing with immunosuppressants for islet transplantation, (4) prolonging drug pharmacokinetics, and (5) retarding diabetic nephropathy..

A Review of the Efficacy and Cardiovascular Safety of Amylin Analogues.

Koshy, Rithika Mary · 2021

Pramlintide with insulin reduces HbA1c and weight with minimal/no hypoglycemia in T1DM and T2DM.

Proglucagon-Derived Peptides as Therapeutics.

Lafferty, Ryan A · 2021

Proglucagon-derived peptide family includes glucagon, GLP-1, GLP-2, oxyntomodulin, glicentin, and GRPP.

Induction of diabetes in cynomolgus monkey with one shot of analytical grade streptozotocin.

Liu, Zhengzhao · 2020

Single 100 mg/kg dose of analytical-grade STZ induced complete diabetes in cynomolgus monkeys with destroyed beta cells and <0.5 ng/mL stimulated C-peptide, without organ toxicity..

Modulation of Sensory Nerve Function by Insulin: Possible Relevance to Pain, Inflammation and Axon Growth.

Lázár, Bence András · 2020

Insulin receptors are expressed on a specific subset of sensory neurons in both the central and peripheral nervous system.

Effects of glucagon-like peptide-1 receptor agonists on major cardiovascular events in patients with Type 2 diabetes mellitus with or without established cardiovascular disease: a meta-analysis of randomized controlled trials.

Marsico, Fabio · 2020

GLP-1 receptor agonists reduced 3-point MACE by 12% (HR 0.88), stroke by 16%, CV death by 12%, all-cause mortality by 11%, and HF hospitalization by 8% across 56,004 patients — with no significant difference between those with or without established CVD..

Major cardiovascular events, heart failure, and atrial fibrillation in patients treated with glucagon-like peptide-1 receptor agonists: An updated meta-analysis of randomized controlled trials.

Nreu, Besmir · 2020

GLP-1 RAs significantly reduced MACE (OR 0.87), all-cause mortality (OR 0.89), and showed a trend toward heart failure reduction (OR 0.93) without increasing atrial fibrillation risk across 43 trials..

Expression of Gastrin Family Peptides in Pancreatic Islets and Their Role in β-Cell Function and Survival.

Khan, Dawood · 2018

Gastrin family peptides — specifically a modified CCK fragment called (pGlu-Gln)-CCK-8 and gastrin-17 — directly stimulate insulin secretion from pancreatic beta cells and promote beta-cell growth and survival.

Efficacy and Safety of Liraglutide Added to Insulin Treatment in Type 1 Diabetes: The ADJUNCT ONE Treat-To-Target Randomized Trial.

Mathieu, Chantal · 2016

Adding liraglutide to insulin therapy in type 1 diabetes modestly improved blood sugar control (HbA1c reduced 0.20% more than placebo at the 1.8 mg dose), reduced total insulin requirements by 8%, and produced significant weight loss (up to 4.9 kg at 1.8 mg vs placebo).