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

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

Comparative Efficacy of a Two Daily Mixed Insulin Injection Versus a Basal-bolus Scheme With Human Insulin (clinicaltrials.gov) - P4 | N=22 | Completed | Sponsor: Université NAZI BONI | Recruiting ➔ Completed

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

Core-shell aerogel design for enhanced oral insulin delivery. (PubMed, Int J Pharm) - "This study focused on the development and characterization of both conventional and core-shell aerogels derived from natural polysaccharides for the oral delivery of insulin, utilizing Humulin R® U-100 as the insulin source for the first time...A notable difference in encapsulation efficiencies was observed between conventional (12 %) and core-shell (53 %) aerogels, highlighting the superior carrier characteristics of the latter ones. In vitro insulin release profiles from the core-shell aerogels demonstrated their potential suitability for delivering regular/short-acting insulin therapeutics since only 30 % of insulin was released in Simulated Gastric Fluid (SGF) after 120 min, whereas 60 % of insulin was released in Simulated Intestinal Fluid (SIF) within the first hour followed by a sustained release stage."

Journal • Targeted Protein Degradation

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: Feb 2025 ➔ Dec 2025 | Trial primary completion date: Dec 2024 ➔ Oct 2025

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

TREATING DIABETIC KETOACIDOSIS IN A PATIENT ALLERGIC TO REGULAR INSULIN (CHEST 2024) - "Initial serology concerning forDKA but unable to start an insulin drip given documented anaphylactic reaction to Humulin-R...This was performed on the patient, and he was treated with NovoLog subcutaneous dosing every 2 hours for treatment of DKA.While no standardized protocol exists for insulin desensitization, various ultra-rush desensitization protocols advocate using Insulin preparations of decreasing concentrations (1:10, 1:100, 1:1000), given in small increments to patients (doses vary from 0.001 unit to 0.1 unit per dose)...This is done in a monitored setting with equipment to treat anaphylaxis, including epinephrine, diphenhydramine, intravenous fluid, and readily available steroids... Insulin is vital to the treatment of diabetes and its life-threatening complications, including DKA. Allergy to the insulin molecule is rare and poses challenges to treatment in the critical care unit. Using a less immunogenic formulation and/or a rapid desensitization protocol may..."

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

SNIFF - Combo INI+EMPA Trial (clinicaltrials.gov) - P2 | N=30 | Completed | Sponsor: Wake Forest University Health Sciences | Recruiting ➔ Completed | N=60 ➔ 30 | Trial completion date: Oct 2028 ➔ Sep 2024 | Trial primary completion date: Oct 2026 ➔ Sep 2024

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

SNIFF Multi-Device Study 2 (clinicaltrials.gov) - P2 | N=30 | Suspended | Sponsor: Wake Forest University Health Sciences | Trial completion date: Oct 2026 ➔ Oct 2027 | Active, not recruiting ➔ Suspended | Trial primary completion date: Oct 2025 ➔ Oct 2026

Trial completion date • Trial primary completion date • Trial suspension • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • APP • CSF Aβ42

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

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

Safety of Topical Insulin Drops for Open-angle Glaucoma (clinicaltrials.gov) - P1 | N=18 | Active, not recruiting | Sponsor: Centre hospitalier de l'Université de Montréal (CHUM) | Recruiting ➔ Active, not recruiting

Enrollment closed • Glaucoma • Hypoglycemia • Ophthalmology

Human Models of Selective Insulin Resistance: Pancreatic Clamp (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Columbia University

New P1 trial • Genetic Disorders • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

Dexamethasone/Pancreatic Clamp P&F (clinicaltrials.gov) - P1 | N=0 | Withdrawn | Sponsor: Columbia University | N=16 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Genetic Disorders • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

Severe Insulin Resistance in a Patient with Graft-Versus-Host Disease (GvHD) (AACE 2024) - "The patient was on an insulin pump using Humulin R U-500 with a total daily basal insulin dose of 72 units (72 x 5 = 360 units of U-100 insulin) and boluses of 15-50 units of U-500 insulin three times daily with meals (equivalent to 225-750 units of U-100 insulin), resulting in a total daily requirement of up to 1,110 units. The patient was previously on metformin extended release 500 mg nightly and empagliflozin 10 mg daily, which had recently been held due to worsening renal function...Post-transplant DM (PTDM) complicated by cGvHD is an under-recognized complication with an unclear pathophysiologic basis. Further studies are needed to elucidate the mechanisms driving severe insulin resistance in these patients."

Clinical • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Cardiovascular • Chronic Kidney Disease • Congestive Heart Failure • Diabetes • Dyslipidemia • Endocrine Disorders • Genetic Disorders • Graft versus Host Disease • Heart Failure • Hematological Malignancies • Hypertension • Immunology • Leukemia • Lymphoma • Metabolic Disorders • Nephrology • Obesity • Oncology • Transplantation

Safety of Topical Insulin Drops for Open-angle Glaucoma (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Centre hospitalier de l'Université de Montréal (CHUM) | Trial primary completion date: Feb 2024 ➔ Jul 2024

Trial primary completion date • Glaucoma • Hypoglycemia • Ophthalmology