Humulin R (recombinant human insulin) / Alzheimer's Disease Cooperative Study, Eli Lilly - LARVOL DELTA

Extreme Steroid-Induced Insulin Resistance in A Patient with Lupus Nephritis (ENDO 2026) - "Despite aggressive escalation of therapy, including basal insulin up to 60 units twice daily, prandial insulin up to 35 units three times daily, and addition of pioglitazone, daily insulin requirements peaked at 1,704 units...Hyperglycemia persisted for over 10 days, gradually improving, as steroids were tapered to prednisone 30 mg daily. Due to ongoing insulin resistance, therapy was transitioned from IV insulin to concentrated regular insulin (Humulin R U-500) at 80 units three times daily before meals... Extreme steroid-induced insulin resistance, requiring aggressive insulin therapy, concentrated insulin formulations, and coordinated multidisciplinary management, is an exceptionally rare phenomenon. Early recognition of this condition is essential to ensure safe and effective glucose control during high-dose glucocorticoid therapy"

Clinical • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Diabetic Nephropathy • Glomerulonephritis • Heart Failure • Hypoglycemia • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Lupus Nephritis • Metabolic Disorders • Nephrology • Pancreatic Cancer • Renal Disease • LEP

Novel Use of Humulin R U-500 in an Automated Insulin Delivery System Results in Stable Glycemic Control, Decreased Insulin Requirements, and Reduced Diabetes Burden in A Patient with Type 1 Diabetes and Severe Insulin Resistance (ENDO 2026) - "The use of U-500R in an AID system provided meaningful benefits for a patient with severe insulin resistance, resulting in decreased total daily insulin dose and less frequent infusion set changes while maintaining glycemic stability. Despite theoretical risks of stacking, delayed action, and nocturnal hypoglycemia, no significant increase in TBR was observed. Further studies are needed to define optimal pump parameters, absorption kinetics, and long-term safety."

Clinical • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus

Treatment of Subcutaneous Insulin Resistance Syndrome with Co-Administered Subcutaneous Heparin and Insulin (ENDO 2026) - "She required Dexamethasone 4mg daily for treatment...Escalating subcutaneous insulin requirements and transition to Humulin R U-500 did not achieve glycemic control...On discharge, we recommended therapy with insulin lispro–aabc 32 units with meals which has been shown to aid insulin absorption through Treprostinil and citrate. Given the paucity of reported cases, our report emphasizes the need for awareness, timely diagnosis, and prompt initiation of appropriate therapy for Subcutaneous Insulin Resistance Syndrome."

Diabetes • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Immunology • Lymphoma • Marginal Zone Lymphoma • Metabolic Disorders • Rare Diseases • Type 1 Diabetes Mellitus

Recurrent Antecedent Intranasal Insulin Blunts the Epinephrine Response to Hypoglycemia (ADA 2026) - "One group received recurrent intranasal insulin (RINI, 0.6U Humulin R) while a control group received recurrent intranasal saline (RINSAL)... In the absence of systemic glucose lowering effects, recurrent intranasal insulin preconditioning may act centrally to blunt the glucoregulatory and sympathoadrenal response to subsequent hypoglycemia."

Hypoglycemia • Metabolic Disorders

LEV PS: Dose Response Study of Transdermal Human Insulin in Patients (clinicaltrials.gov) - P2/3 | N=30 | Not yet recruiting | Sponsor: Transdermal Delivery Solutions Corp | Trial completion date: Dec 2025 ➔ Dec 2027 | Trial primary completion date: Oct 2025 ➔ Oct 2027

Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders

Insulin Versus Oral Hypoglycemic Agents in Gestational Diabetes Mellitus (clinicaltrials.gov) - P=N/A | N=60 | Completed | Sponsor: Dr Mudassar Saeed Pansota

New trial • Diabetes • Gestational Diabetes • Hypoglycemia • Metabolic Disorders

SNIFF Multi-Device Study 2 (clinicaltrials.gov) - P2 | N=13 | Completed | Sponsor: Wake Forest University Health Sciences | N=30 ➔ 13 | Suspended ➔ Completed

Enrollment change • Trial completion • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • CSF Aβ42

Human Models of Selective Insulin Resistance: Pancreatic Clamp (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Columbia University | Trial completion date: Feb 2028 ➔ Feb 2029 | Trial primary completion date: Dec 2027 ➔ Dec 2028

Trial completion date • Trial primary completion date • Familial Chylomicronemia Syndrome • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

Pharmacokinetic and Pharmacodynamic Effects of Insulex® R in Comparison to Humulin® R in Healthy Subjects (clinicaltrials.gov) - P1 | N=40 | Completed | Sponsor: Laboratorios Pisa S.A. de C.V.

New P1 trial

A Single Bolus, 12-hour Euglycemic Clamp Study of the Safety, Pharmacokinetics (PK) and Glucodynamics (GD) of Intraperitoneal (IP) Portal Insulin U-500 (clinicaltrials.gov) - P1 | N=25 | Recruiting | Sponsor: Portal Diabetes, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

A Single Bolus, 12-hour Euglycemic Clamp Study of the Safety, Pharmacokinetics (PK) and Glucodynamics (GD) of Intraperitoneal (IP) Portal Insulin U-500 (clinicaltrials.gov) - P1 | N=25 | Not yet recruiting | Sponsor: Portal Diabetes, Inc.

New P1 trial • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

IAA: Insulin and Abatacept in Recently-diagnosed Type 1 Diabetes (clinicaltrials.gov) - P2 | N=68 | Completed | Sponsor: Melbourne Health | Trial completion date: Feb 2027 ➔ Sep 2025 | Trial primary completion date: Feb 2026 ➔ Sep 2025 | Active, not recruiting ➔ Completed

Trial completion • Trial completion date • Trial primary completion date • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

SNIFF - Combo INI+EMPA Trial (clinicaltrials.gov) - P2 | N=47 | Completed | Sponsor: Wake Forest University Health Sciences | N=30 ➔ 47

Enrollment change • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • CSF Aβ42

Human Models of Selective Insulin Resistance: Pancreatic Clamp (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Columbia University | Initiation date: Jun 2025 ➔ Jan 2026

Trial initiation date • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

Study of Nasal Insulin to Fight Forgetfulness - Device Study (clinicaltrials.gov) - P2 | N=20 | Completed | Sponsor: Wake Forest University Health Sciences | Active, not recruiting ➔ Completed | N=30 ➔ 20

Enrollment change • Trial completion • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Non-invasive detection of protein aggregation in biopharmaceuticals using TD-NMR and MRI. (PubMed, Eur J Pharm Biopharm) - "For the first time, Magnetic Resonance Imaging (MRI), T2 relaxation times, and T2 relaxation spectra were applied to detect aggregation in Humulin R, a low-concentration subcutaneous insulin...Additionally, T2-Inverse Laplace Transform (ILT) indicated aggregate size, aligning with particle size analysis and validating the novel approach. These findings highlight the potential of low-field NMR for biopharmaceutical quality assessment."

Journal

Acquired Generalized Lipodystrophy Treated With Metreleptin in a Patient With Total Body Irradiation and Chronic Graft-Versus-Host Disease (ENDO 2025) - "The patient was treated with statin, fish oil, gemfibrozil, Humulin R U-500 insulin, insulin pump, pioglitazone, and multiple oral hypoglycemic agents, and her metabolic complications were refractory to these standard therapies. Childhood cancer survivors with a history of TBI and HSCT can develop acquired lipodystrophy with associated metabolic complications later in life. This case demonstrates the role of metreleptin in improving insulin sensitivity and lipoprotein profiles in a patient with AGL."

Clinical • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Diabetes • Dyslipidemia • Endocrine Disorders • Fibrosis • Graft versus Host Disease • Hematological Malignancies • Hepatology • Hypertriglyceridemia • Immunology • Lipodystrophy • Lymphoma • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Non-Hodgkin’s Lymphoma • Oncology • Pain • Rare Diseases • Severe Hypertriglyceridemia • Type 2 Diabetes Mellitus

Role of Omnipod 5 Automated Insulin Infusion on Glucose Management in Patient with Anti-Insulin Antibodies (ENDO 2025) - "Previous management included metformin, Humalog 16 units before each meal, and Levemir 39 units at night. We believe this demonstrates successful management of the rare disorder of insulin autoimmune syndrome with the use of HumuLIN R U-200 insulin through Insulin Pump. Through multiple medication and treatment adjustments this patient's case shows an improvement over the course of treatment that can be used for future tests and trials."

Clinical • Cardiovascular • Diabetes • Dyslipidemia • Hypertension • Hypoglycemia • Immunology • Metabolic Disorders • Obstructive Sleep Apnea • Pain • Rare Diseases • Respiratory Diseases • Sleep Disorder • Type 2 Diabetes Mellitus

A Bariatric Breakthrough in Diabetes Control (ENDO 2025) - "Introduction Type 2 diabetes mellitus (T2DM) and obesity are closely linked, with obesity playing a key role in the development of insulin resistance and acting as a major risk factor for the progression of T2DM...Prior to surgery, her diabetes regimen includes Humulin R U-500 (regular insulin) 135 units daily in the morning and tirzepatide 5 mg weekly...After surgery, as visceral fat decreases, adiponectin levels rise, appears to be predictive of improved insulin resistance.ConclusionThis case exemplifies the potential benefits of bariatric surgery in improving glycemic control and suggests that such procedures may offer long-term improvements in diabetes management. It also highlights the significant reduction in medication burden, as patients no longer need to perform multiple daily insulin injections, leading to greater convenience and less stress in their daily routines – ultimately improving their quality of life."

Asthma • Diabetes • Gastrointestinal Disorder • Genetic Disorders • Immunology • Metabolic Disorders • Obesity • Pain • Respiratory Diseases • Type 2 Diabetes Mellitus

Acquired Generalized Lipodystrophy Treated With Metreleptin in a Patient With Total Body Irradiation and Chronic Graft-Versus-Host Disease (ENDO 2025) - "The patient was treated with statin, fish oil, gemfibrozil, Humulin R U-500 insulin, insulin pump, pioglitazone, and multiple oral hypoglycemic agents, and her metabolic complications were refractory to these standard therapies. Childhood cancer survivors with a history of TBI and HSCT can develop acquired lipodystrophy with associated metabolic complications later in life. This case demonstrates the role of metreleptin in improving insulin sensitivity and lipoprotein profiles in a patient with AGL."

Clinical • Bone Marrow Transplantation • Chronic Graft versus Host Disease • Diabetes • Dyslipidemia • Endocrine Disorders • Fibrosis • Graft versus Host Disease • Hematological Malignancies • Hepatology • Hypertriglyceridemia • Immunology • Lipodystrophy • Lymphoma • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Non-Hodgkin’s Lymphoma • Oncology • Pain • Rare Diseases • Severe Hypertriglyceridemia • Type 2 Diabetes Mellitus

SNIFF - 3-Week Aptar CPS Device (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Wake Forest University Health Sciences | N=40 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • CSF Aβ42

RAPID INSULIN KINETICS FOLLOWING BOLUS INTO VASCULARIZED MICROCHAMBERS IMPLANTED SUBCUTANEOUSLY IN DIABETIC PIGS (ATTD 2025) - "Insulin tolerance tests (ITT) with 5U of HumulinR were performed under light anesthesia...Surprisingly, the 0.6cm2 smallest microchamber exhibited superior pharmacokinetics compared to larger prototypes- reducing AUC for plasma [insulin].Conclusions Insulin bolus at clinically relevant dose through vascularized microchambers improved pharmacokinetics – with faster time to peak insulin and greater insulin clearance. The small footprint of the microchambers are compatible with existing insulin delivery systems thus practical for clinical use."

Anesthesia • Fibrosis • Immunology

Impact of insulin storage and syringe reuse on insulin sterility in diabetes mellitus patients in Mwanza Tanzania. (PubMed, Sci Rep) - "Contaminated products included Humulin R, Humulin N, and Biosulin 30/70. Improper storage practices, such as immersing vials in water or a mixture of water and sand within clay pots expose insulin to microbial contamination, which increases the risk of infections. To ensure safety and effectiveness patients should be educated to follow the manufacturer's storage guidelines."

Journal • Diabetes • Infectious Disease • Metabolic Disorders

HYA ameliorated postprandial hyperglycemia in type 1 diabetes model rats with bolus insulin treatment. (PubMed, Acta Diabetol) - "Oral administration of HYA immediately before OGTT ameliorated postprandial hyperglycemia through inhibition of glucose absorption and slowing of gastric motility in normal rats. Furthermore, this beneficial effect of HYA was also revealed in T1DM rats injected with bolus insulin."

Journal • Preclinical • Diabetes • Metabolic Disorders • Type 1 Diabetes Mellitus

Human Models of Selective Insulin Resistance: Pancreatic Clamp (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Columbia University | Trial completion date: Feb 2027 ➔ Feb 2028 | Initiation date: Dec 2024 ➔ Jun 2025 | Trial primary completion date: Dec 2026 ➔ Dec 2027

Trial completion date • Trial initiation date • Trial primary completion date • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity