Nesina (alogliptin) / Takeda, AbbVie - LARVOL DELTA

Incremental cardiovascular benefit of GLP-1RA added to SGLT2i in type 2 diabetes: a target trial emulation in the US veterans health administration (ESC 2026) - "Background SGLT-2i use was predominantly empagliflozin (>99%). Eighty-seven percent of GLP-1RA initiators received semaglutide; 94% of DPP-4i initiators received alogliptin...Findings were consistent across pre-specified high-risk subgroups, including body mass index, prevalent cardiovascular disease, and baseline AHA PREVENT 10-year cardiovascular-kidney-metabolic risk equation.ConclusionsIn this large target trial emulation of adults with type 2 diabetes receiving SGLT-2i therapy, add-on GLP-1RA was associated with significant reductions in major adverse cardiovascular events compared with DPP-4i, with consistent directional reductions across individual cardiovascular outcomes. These findings support combination GLP-1RA and SGLT-2i therapy as a strategy to further reduce residual cardiovascular risk in clinical practice."

Atherosclerosis • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction

GLP-1 Receptor Agonists Versus DPP-4 Inhibitors and 1-Year Outcomes in Inflammatory Bowel Disease With Type 2 Diabetes or Obesity: A Propensity-Matched Analysis (ACG 2026) - " Using the TriNetX Research Network of 111 healthcare organizations, we identified adults with Crohnâs disease or ulcerative colitis and T2DM or BMI â¥30 kg/m2 receiving GLP-1RA therapy (semaglutide, liraglutide, dulaglutide, or tirzepatide) or DPP-4i therapy (sitagliptin, linagliptin, saxagliptin, or alogliptin)... After matching, 11,720 GLP-1RA users were compared with 11,720 DPP-4i users. GLP-1RA use was associated with lower hospitalization (25.0% vs 31.4%; RR 0.80, 95% CI 0.76-0.83), mortality (3.1% vs 6.0%; RR 0.52, 95% CI 0.46-0.59), systemic corticosteroid initiation (14.4% vs 16.2%; RR 0.89, 95% CI 0.81-0.98), IBD-related bowel surgery (0.6% vs 1.0%; RR 0.61, 95% CI 0.45-0.81), C. difficile infection (1.0% vs 1.4%; RR 0.69, 95% CI 0.54-0.88), bowel obstruction (1.6% vs 2.1%; RR 0.78, 95% CI 0.64-0.95), and advanced IBD therapy initiation or escalation (2.0% vs 2.6%; RR 0.77, 95% CI 0.65-0.92). Gastroparesis did not differ (0.7% vs 0.8%; RR 0.89,..."

Crohn's disease • Diabetes • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Infectious Disease • Inflammation • Inflammatory Bowel Disease • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus • Ulcerative Colitis

GLP-1 Receptor Agonists vs DPP-4 Inhibitors and Cardiovascular Outcomes in Liver Transplant Recipients: A Propensity Score-Matched Active Comparator New-User Analysis of 3,606 Patients (ACG 2026) - "Adults with liver transplant status (Z94.4) and type 2 diabetes (E11.x) or obesity (E66.x) who were new users of GLP-1RA (semaglutide, dulaglutide, liraglutide, exenatide, tirzepatide) or DPP-4i (sitagliptin, saxagliptin, alogliptin, linagliptin) were identified using a 365-day washout for both drug classes... After matching, 1,803 pairs were identified. Post-match standardized mean differences were < 0.10 for all demographic and clinical covariates. GLP-1RA was associated with significantly lower 3-point MACE (HR 0.82, 95%CI 0.69â0.97, p=0.001)."

Clinical • Cardiovascular • Congestive Heart Failure • Diabetes • Genetic Disorders • Heart Failure • Ischemic stroke • Metabolic Disorders • Myocardial Infarction • Obesity • Pancreatitis • Transplant Rejection • Transplantation • Type 2 Diabetes Mellitus

High-Sensitivity C-Reactive Protein, All-Cause Mortality and Heart Failure Hospitalization After Acute Coronary Syndrome in Type 2 Diabetes: Insights from the Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care (EXAMINE) Trial (AHA 2026) - "Abstract is embargoed at this time."

Clinical • Acute Coronary Syndrome • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Type 2 Diabetes Mellitus • CRP

Alogliptin mitigates doxorubicin-induced cardiotoxicity in rats: Implications of SIRT3/NRF2 pathway and miRNA-133a. (PubMed, Tissue Cell) - "However, these results are limited by the inspection lack of echocardiography or hemodynamic alterations, gain and loss of function, caspase activation, and mitochondrial health tests. Thus, ALO has the potential to be an appropriate therapy for DOX-induced cardiotoxicity."

IO biomarker • Journal • Preclinical • Cardiovascular • Oncology • BCL2 • IL6 • SIRT3 • TGFB1 • TNFA

Dipeptidyl Peptidase-4 Inhibitors Associated Heart Failure Events in Adult Patients With Type-2 Diabetes Mellitus Treated With Dipeptidyl Peptidase-4 Inhibitors: A Systematic Review and Meta-Analysis. (PubMed, Endocrinol Diabetes Metab) - "Results should be interpreted with caution because of several limitations of the study."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Metabolic Disorders • Pediatrics • Type 2 Diabetes Mellitus

Alogliptin Enhances Implant Osseointegration in Diabetes Through an Osteogenic-Angiogenic Immunomodulatory Procedure. (PubMed, Int J Mol Sci) - "Alogliptin has positive effects on the oral implant health of people with diabetes. A locally delivered GelMA-alogliptin hydrogel system exhibits competitive ability to improve diabetic bone microenvironment and enhance implant osseointegration."

Journal • Diabetes • Inflammation • Metabolic Disorders • Osteoporosis • GSK3B

Trace Analysis of Genotoxic Impurity 3-Amino-N-Nitrosopiperidine in Alogliptin Benzoate by Ultra-Sensitive Liquid Chromatography Tandem Mass Spectrometry. (PubMed, Biomed Chromatogr) - "In 2018 EMA and USFDA claimed the presence of N-nitrosodimethylamine in valsartan used for the treatment of hypertension. Also, spiking study was performed by the calculating percentage spiked NTPA in the drug, which ranged from 96.67% to 100.14%. The results confirmed that the methodology was reliable, precise, robust and reproducible to quantify NTPA at 1.5 ppm in samples of 2.75 mg/mL concentration."

Journal • Cardiovascular • Hypertension

Comparison of the permeability of DPP-4 inhibitors-sitagliptin, vildagliptin, linagliptin, and alogliptin-in placental barrier cell models and exploration of their transport mechanisms by LC-MS/MS. (PubMed, BMC Pregnancy Childbirth) - "Vildagliptin had the lowest accumulation and permeability in placental cells among the four DPP-4 inhibitors. There might be carrier-mediated transmembrane transport of linagliptin, alogliptin, sitagliptin and vildagliptin, but ENTs, CNTs and OAT4 were not involved in. This study provides a basis for future research on their safety during pregnancy."

Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

From glycemic control to neuroprotection: alogliptin as a repurposed candidate for Huntington's disease. (PubMed, Metab Brain Dis) - "This review identifies alogliptin as a potent repurposable agent and the necessity to conduct specific experimental and clinical research to determine its effectiveness in refining symptoms and changing the disease course in HD. This narrative review critically evaluates the available experimental evidence supporting the repurposing potential of Alogliptin for HD."

Journal • Review • CNS Disorders • Cognitive Disorders • Huntington's Disease • Inflammation • Mental Retardation • Metabolic Disorders • Movement Disorders • Psychiatry

Comparative Effectiveness of Glucagon-like Peptide-1 Receptor Agonists Versus Oral Agents for Insulin Discontinuation in Type 2 Diabetes : A Target Trial Emulation. (PubMed, Ann Intern Med) - "Among 8869 matched sets of GLP-1RA (76.6% semaglutide, 15.2% dulaglutide, 7.9% liraglutide, and 0.3% exenatide), SGLT-2i (99.7% empagliflozin), and DPP-4i (95.9% alogliptin) initiators, 63% were 65 years or older, 93% were male, 70% were White, and 48% had a hemoglobin A1c (HbA1c) level of 9% or more. U.S. Department of Veterans Affairs."

HEOR • Journal • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

RETRACTED: Mohanty et al. Formulation and Optimization of Alogliptin-Loaded Polymeric Nanoparticles: In Vitro to In Vivo Assessment. Molecules 2022, 27, 4470. (PubMed, Molecules) - "The journal retracts the article titled "Formulation and Optimization of Alogliptin-Loaded Polymeric Nanoparticles: In Vitro to In Vivo Assessment" [...]."

Journal • Preclinical

Repurposing of alogliptin to mitigate experimentally-induced ulcerative colitis and its associated pulmonary injury in rats through regulating inflammatory, necroptotic, and ER stress pathways. (PubMed, Eur J Pharmacol) - "These outcomes subsequently prevented the pulmonary injury associated with TLR4/NF-κB p65/TNF-α, RIPK1/MLKL/HMGB1, IRE-1α/p-JNK, oxidative stress, and TGF-β1/COL1A1/COL3A1 cascades with notable anti-fibrotic effects. In this context, ALO could be a promising nominee for the treatment of UC and its associated pulmonary injury through attenuating colonic inflammation, preserving gut integrity, and preventing systemic inflammation and its associated lung-induced injury."

Journal • Preclinical • Fibrosis • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Pneumonia • Respiratory Diseases • Ulcerative Colitis • CLDN1 • COL1A1 • COL3A1 • HMGB1 • RIPK1 • TGFB1 • TLR4 • TNFA

Latent Autoimmune Diabetes in Adults Unmasked by SGLT2 Inhibitor-Associated Euglycemic Diabetic Ketoacidosis (ENDO 2026) - "His history was notable for progressively worsening glycemic control despite escalating oral therapy, including empagliflozin/metformin, glipizide, pioglitazone, and alogliptin, with a glycosylated hemoglobin (HbA1c) of 11.3%. The combination of young age, non-obesity, and treatment failure on multiple oral agents should prompt autoantibody and C-peptide testing. SGLT2 inhibitors are not approved for type 1 diabetes and should not be used in patients with insulin-deficient states or prior diabetic ketoacidosis."

Clinical • Diabetes • Genetic Disorders • Immunology • Infectious Disease • Metabolic Disorders • Obesity • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus

Early potential safety signals for gliptins and gliflozins using real-world pharmacy data compared to spontaneous reporting. (PubMed, PLoS One) - "Community pharmacy real-world data may contribute to the early identification of potential safety signals that complement spontaneous reporting systems. Signals detected near the exploratory threshold should be interpreted cautiously and considered candidates for monitoring and further investigation rather than confirmed adverse drug reactions."

Journal • Observational data • Real-world evidence • Retrospective data • Dermatology • Diabetes • Infectious Disease • Musculoskeletal Diseases • Nephrology • Orthopedics • Pruritus • Renal Disease • Xerostomia

Phosphatidylinositol-3-kinase/Protein Kinase B (PI3K/AKT) and Nucleotide-Binding Oligomerization Domain-like Receptor Family Pyrin Domain Containing 3 (NLRP3) Inflammasome Modulation Underlies the Neuroprotective Effects of Vildagliptin in a Rotenone-Induced Mouse Model of Parkinson's Disease. (PubMed, ACS Pharmacol Transl Sci) - "In silico analyses, including molecular docking as well as molecular dynamics simulation, demonstrate good binding affinity as well as stable interaction of vildagliptin with PI3K (4YKN) and NLRP3 (7ALV) proteins in comparison to other DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin, and alogliptin). These findings collectively suggest that vildagliptin rendered neuroprotection by PI3K/AKT activation and inhibition of NLRP3-mediated neuroinflammation and apoptosis. In conclusion, we can say that vildagliptin possesses definitive neuroprotective potential as a disease-modifying therapy that warrants further clinical exploration."

Journal • Preclinical • CNS Disorders • Diabetes • Inflammation • Metabolic Disorders • Movement Disorders • Parkinson's Disease • Type 2 Diabetes Mellitus • IL1B • NLRC5 • NLRP3

Comparative Effects of Antidiabetic Drugs on Body Composition: A Systematic Review and Network Meta-Analysis. (PubMed, Diabetes Obes Metab) - "GLP-1 and dual GIP/GLP-1 receptor agonists produced the greatest FM reduction but also decreased lean mass. Exercise mitigated liraglutide-related LBM loss. SGLT2 inhibitors showed modest effects, while metformin, insulin, DPP4 inhibitors and sulfonylureas had minimal impact. Further research on dose, duration and lifestyle influences is warranted."

Journal • Retrospective data • Review

Alogliptin attenuates diabetes-associated cognitive impairment in rats via HMGB1/RAGE/TLR4-NFκB pathway modulation. (PubMed, Biomed Pharmacother) - "Alogliptin also refined mTOR signaling pathway and improved neuronal health. According to these findings, alogliptin reduces neuroinflammation and alters mTOR action leading to the improvement of neurodegeneration and memory function."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Diabetes • Inflammation • Metabolic Disorders • Type 2 Diabetes Mellitus • HMGB1 • IL1B • TLR4 • TNFA

Alogliptin-metformin synergy ameliorates diabetes-associated bone loss via modulation of DPP-4 activity and OPG/RANKL signaling. (PubMed, 3 Biotech) - "Moreover, both alogliptin and metformin exhibited dose-dependent effects, and the 1:8 alogliptin-metformin ratio demonstrated strong synergism (CI 0.04388). These findings suggest that alogliptin-metformin co-therapy ameliorates diabetes-associated skeletal complications through modulation of DPP-4 activity and OPG/RANKL signaling."

Journal • Diabetes • Metabolic Disorders • Musculoskeletal Diseases • Obesity • Oncology • Orthopedics • Osteoporosis • Type 2 Diabetes Mellitus • IL6 • TNFA • TNFRSF11B • TRAP

Novel gastroprotective role of Alogliptin: Modulating the GDNF/PI3K/Akt/GSK3β, SDF-1/CXCR4, and CREB/COX-2/PGE2 signalling pathways to ameliorate diclofenac-induced peptic ulcer in rats. (PubMed, Eur J Pharmacol) - "Rats were randomly allocated into four groups: a control group receiving saline for 14 days; Diclofenac group administered diclofenac (50 mg/kg/day, i.p., days 8-14) to induce gastric ulceration; and two pretreatment groups receiving either omeprazole (20 mg/kg/day, p.o.) or alogliptin (40 mg/kg/day, p.o.) for 14 days, concomitantly with diclofenac administration during days 8-14. Furthermore, Alogliptin suppressed NF-κB/TNF-α-driven inflammation, mitigated oxidative stress, as evidenced by decreased MDA and increased SOD activity, and shifted the apoptotic balance toward cell survival by reducing Bax and elevating Bcl-2 levels. Ultimately, alogliptin exerts multifaceted gastroprotective effects against diclofenac-induced gastric ulcer by enhancing mucosal defense and orchestrating anti-inflammatory, antioxidant, and anti-apoptotic mechanisms through interplay between GDNF/PI3K/Akt, CREB/COX-2/PGE2, and SDF-1/CXCR4 trajectories."

IO biomarker • Journal • Preclinical • Gastroenterology • Inflammation • Pain • Peptic Ulcer • BCL2 • CXCL12 • CXCR4 • PTGS2 • TNFA

CER-4-T2D: Comparative Effectiveness and Safety of Four Second Line Pharmacological Strategies in Type 2 Diabetes Study (clinicaltrials.gov) - P=N/A | N=781430 | Active, not recruiting | Sponsor: Brigham and Women's Hospital | Trial completion date: Jul 2026 ➔ Sep 2027 | Trial primary completion date: Jan 2026 ➔ May 2026

HEOR • Trial completion date • Trial primary completion date • Cardiovascular • Diabetes • Diabetic Nephropathy • Metabolic Disorders • Nephrology • Renal Disease • Type 2 Diabetes Mellitus

Association Between Dipeptidyl Peptidase-4 Inhibitor Use and Acute Kidney Injury in Patients With Diabetes Mellitus: A Disproportionality Analysis Based on the FAERS. (PubMed, In Vivo) - "This study suggests that some DPP4is, including linagliptin, sitagliptin and vildagliptin, are associated with AKI, even without concomitant use of an AKI inducer. Given the widespread use of DPP4is and the severity of AKI, clinicians should be sufficiently informed about their potential relationship."

Journal • Acute Kidney Injury • Diabetes • Metabolic Disorders • Nephrology • Renal Disease

Alogliptin Attenuates Diclofenac-Induced Acute Kidney Injury Associated With Activation of the AKT/Nrf2-mediated Ferroptosis Pathway. (PubMed, J Biochem Mol Toxicol) - "The current study uncovers a novel renoprotective role for alogliptin in mitigating DIC-induced renal injury, potentially mediated by stimulating AKT/Nrf2/SCL7A11/GPX4 signaling axis, with subsequent dampening of lipid peroxidation and ferroptosis, besides its well-known, anti-inflammatory, and antiapoptotic actions. Finally, these findings provide compelling evidence for repurposing alogliptin in combating DIC-triggered kidney damage."

IO biomarker • Journal • Acute Kidney Injury • Inflammation • Nephrology • Renal Disease • ACSL4 • BCL2 • CASP3 • GPX4 • IL6 • KIM1 • SLC7A11 • TNFA

Alogliptin Delays the Healing of Traumatic Oral Ulcers in the Buccal Mucosa of Wistar Rats. (PubMed, Fundam Clin Pharmacol) - "Alogliptin delays oral ulcer healing by sustaining inflammation, reducing TGF-β expression, and impairing collagen deposition, and may contribute via reduced TLR2/TLR4 expression, increased microbial burden, and decreased TGF-β."

Journal • Preclinical • Inflammation • CD31 • PECAM1 • TGFB1 • TLR2 • TLR4

Cardiovascular Effects of Alogliptin, Linagliptin, Saxagliptin, and Sitagliptin: A Target Trial Emulation of a Comparative Effectiveness Study. (PubMed, Endocr Pract) - "Risks of MACE, HHF, and hypoglycemia were comparable with all DPP4i. Choice of medication may be determined based on local availability."

HEOR • Journal • Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Hypoglycemia • Metabolic Disorders • Myocardial Infarction • Type 2 Diabetes Mellitus