What is NPH Insulin (isophane)?

An intermediate-acting insulin made by combining insulin with protamine; also called isophane or NPH insulin (Humulin N, Novolin N).

NPH Insulin (isophane) in the library · · Human Trials · What are peptides?

103 registered trials · 409 indexed papers · 464 human / 1 animal studies

From the PeptideWhiz library entry. "As described" sections summarize claims made in the sources; they are not PeptideWhiz endorsements.

What it is

An intermediate-acting insulin made by combining insulin with protamine; also called isophane or NPH insulin (Humulin N, Novolin N).

Type: Intermediate-acting insulin.

Definition (National Library of Medicine)

“An intermediate-acting insulin preparation with onset time of 2 hours and duration of 24 hours. It is produced by crystallizing zinc-insulin-protamines at neutral pH 7. Thus it is called neutral protamine Hagedorn for inventor Hans Christian Hagedorn.”

MeSH: Insulin, Isophane

Human research

The registered human trials and peer-reviewed human studies linked below are listed from ClinicalTrials.gov and PubMed. A study is linked only when NPH Insulin (isophane) is one of its interventions, or is named in the study title or subject headings.

Listing a study does not mean it showed a benefit, and it is not medical advice.

Registered human trials (103)

Trial	Phase	Status	Year	Enrolled
Pre-emptive Insulin to Prevent High Glucose After a Knee Steroid Injection in Adults With Type 2 Diabetes	Phase 1/Phase 2	active not recruiting	2026	125
RCT Glargine vs NPH for Treatment of DM in Pregnancy	Phase 3	recruiting	2024	160
Comparative Efficacy of a Two Daily Mixed Insulin Injection Versus a Basal-bolus Scheme With Human Insulin	Phase 4	completed	2023	22
DETERMINE: Detemir vs NPH	Phase 2	recruiting	2022	336
Insulin for Hyperglycemia in Stroke Trial	Phase 4	completed	2021	452
Dapagliflozin Effect in Cognitive Impairment in Stroke Trial	Phase 2/Phase 3	unknown	2020	270
Intermediate and Long Acting Insulin Young Children Type 1 Diabetes.	Phase 4	unknown	2019	60
Use of NPH Versus Basal Bolus Insulin for Steroid Induced Hyperglycemia	Phase 4	terminated	2018	3
A Study to Demonstrate Bioequivalence Between Insulin Glulisine U300 and Insulin Glulisine U100 After a Single Subcutaneous Dose Using the Euglycemic Clamp Technique, in Patients With Type 1 Diabetes Mellitus	Phase 1	completed	2017	44
Insulin Schemes for Type 2 Diabetes Control	Phase 4	completed	2017	75
Comparison of Two Biphasic Insulin Regimens		completed	2016	36
Pharmacokinetic (PK) Bioequivalence and Pharmacodynamics (PD) of Julphar Insulin N and Huminsulin® Basal	Phase 1	completed	2016	85
Comparison of Metformin and Insulin for Management of Gestational Diabetes Mellitus	Phase 3	completed	2016	278
A "Real World" Trial to Determine Efficacy and Health Outcomes of Toujeo Compared to "Standard of Care" Basal Insulin in Patients Already Using Basal Insulin	Phase 4	completed	2015	609
A "Real World" Trial to Determine Efficacy and Health Outcomes of Toujeo Compared to "Standard of Care" Basal Insulins in Insulin Naïve Patients Initiating Insulin	Phase 4	completed	2015	705
The Inova Type 2 Diabetes Mellitus Study		withdrawn	2015
A Trial Investigating the Efficacy and Safety of Insulin Detemir Versus Insulin NPH in Combination With Metformin and Diet/Exercise in Children and Adolescents With Type 2 Diabetes Insufficiently Controlled on Metformin With or Without Other Oral Antidiabetic Drug(s) With or Without Basal Insulin	Phase 3	terminated	2014	42
Glucose Control for Glucocorticoid Induced Hyperglycemia During Chemotherapy	Phase 4	completed	2014	26
Comparison Study of Insulin Glargine and NPH Insulin	Phase 4	withdrawn	2013
A Study To Evaluate The Efficacy And Safety Of Ertugliflozin In Participants With Type 2 Diabetes Mellitus And Inadequate Glycemic Control On Metformin Monotherapy (MK-8835-007).	Phase 3	completed	2013	621
A Study to Compare a New Long-Acting Insulin (LY2605541) and Human Insulin NPH in Participants With Type 2 Diabetes	Phase 3	completed	2013	641
Comparator Trial Using Insulin Glulisine vs. Insulin Lispro for Treatment of Gestational Diabetes	Phase 2	completed	2013	17
Glargine Versus NPH in Patients With Chronic Kidney Disease	Phase 4	completed	2013	34
Glycemic Control Using Insulin Levemir Versus Insulin NPH for Diabetes in Pregnancy		completed	2013	105
Insulin Therapy for the Prevention of New Onset Diabetes After Transplantation Prospective Study in Non-Diabetic De Novo Kidney Transplant Recipients	Phase 3	completed	2012	263
Efficacy of Metformin in Achieving Glycaemia Goals as Recommended for the Treatment of Gestational Diabetes in Non Obese Women	Phase 2	terminated	2012	84
Sensor-Augmented Insulin-Pump Therapy in New-onset Diabetes After Transplantation	Phase 3	completed	2012	85
Insulin Therapy for Post-transplant Glucocorticoid Induced Hyperglycemia	Phase 4	terminated	2012	5
Impact of Blood Glucose at the First Trimester of Pregnant Women With Gestational Diabetes on Maternal and Fetal Outcomes and Metabolic Disorders: a Multi-central Prospective Cohort Study		unknown	2012	3
Effect of NPH Insulin, Insulin Detemir and Insulin Glargine on GH-IGF-IGFBP Axis	Phase 3	completed	2012	19
Comparing Efficacy and Safety of Insulin Detemir Plus Insulin Aspart and NPH Insulin Plus Human Soluble Insulin With or Without Metformin in Chinese Patients With Type 2 Diabetes	Phase 4	terminated	2011	58
Efficacy and Safety of Insulin Glargine Versus. Neutral Protamine Hagedorn (NPH) Insulin in Children With Type 1 Diabetes Above 6 Years Old.	Phase 3	completed	2011	162
Cost Effectiveness of Glargine Insulin Versus NPH Insulin	Phase 4	completed	2011	200
Comparative Wockhardt's Glucose Clamp Study-Human Isophane Susp [amount hidden] With Novolin70/30, in Healthy Subjects	Phase 1	completed	2011	53
Establishing Cardiovascular Biomarkers to Define Preferred Lantus® Use	Phase 4	unknown	2011	60
Hospital Insulin Protocol Aims for Glucose Control in Corticosteroid-induced Hyperglycemia	Phase 4	completed	2010	72
The Management of Glucocorticoid-Induced Hyperglycemia in Hospitalized Patients	Phase 4	completed	2010	37
Sitagliptin (DPP-4 Inhibitor) and NPH Insulin in Patients With T2D	Phase 4	completed	2010	40
Evaluation of the Safety and Efficacy of Insulin Glargine + Glulisine or Insulin Regular + NPH Insulin (Isophane Insulin) Use in Type 2 Diabetes Mellitus Patients With Moderate Renal Failure.	Phase 4	completed	2010	72
The Effects of Short-Term Exenatide Therapy in Newly Diagnosed Type 2 Diabetic Patients	Phase 4	unknown	2010	160

Peer-reviewed studies (409)

Paper	Authors	Journal	Year	Type
Empagliflozin improves beta cell function independently of relief of glucotoxicity in patients with type 2 diabetes: results from a randomised cross-over study with insulin as comparator	Thirumathyam R et al.	Diabetologia	2026	Randomized Controlled Trial
MicroRNAs modulated by DPP-4 inhibitor and bedtime NPH insulin therapy in individuals with type 2 diabetes	Santos AS et al.	Frontiers in endocrinology	2025	Randomized Controlled Trial
Early use of neutral Protamine Hagedorn (NPH) insulin in the management of diabetic ketoacidosis: an open-label randomized controlled trial in a resource-limited setting	Baby N et al.	BMC research notes	2025	Randomized Controlled Trial
Human versus Analogue Insulin for Youth with Type 1 Diabetes in Low-Resource Settings (HumAn-1): protocol for a randomised controlled trial	Foulds A et al.	BMJ open	2025	Clinical Study
Outpatient diabetes management influences glycemic control for critically ill patients during nutrition support: A retrospective observational study	Dickerson RN et al.	Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition	2025	Observational Study
Effect of needle-free injection on psychological insulin resistance and insulin dosage in patients with type 2 diabetes	Wang W et al.	Frontiers in endocrinology	2024	Randomized Controlled Trial
Glycaemic outcomes in hospital with IDegAsp versus BIAsp30 premixed insulins	Walt JR et al.	Internal medicine journal	2024	Observational Study
Charitable medication distribution improves care for uninsured patients with diabetes	Hughes J et al.	The American journal of managed care	2023	Observational Study
Real-world study of ethnic differences in glycaemic control and clinical characteristics among insulin-naïve people with type 2 diabetes initiating biphasic insulin aspart 30/70: A retrospective, observational cohort study in England	Davies MJ et al.	Diabetes, obesity & metabolism	2023	Observational Study
[Cost-effectiveness of treatment of type 2 diabetes mellitus in México]	Pérez-Lozano DL et al.	Revista medica del Instituto Mexicano del Seguro Social	2023	Observational Study
Pharmacokinetic and pharmacodynamic equivalence of Biocon's biosimilar insulin N with US-licensed Humulin® N formulation in healthy subjects: Results from the RHINE-2 (Recombinant Human INsulin Equivalence-2) study	Andersen G et al.	Diabetes, obesity & metabolism	2023	Randomized Controlled Trial
The efficacy and safety of GP40081 (insulin aspart biphasic 30) compared with NovoMix(®) 30 in Type 2 diabetes patients	Drai RV et al.	Journal of comparative effectiveness research	2022	Randomized Controlled Trial
Hypoglycemic events and glycemic control effects between NPH and premixed insulin in patients with type 2 diabetes mellitus: A real-world experience at a comprehensive specialized hospital in Ethiopia	Sendekie AK et al.	PloS one	2022	Observational Study
One week of overeating upregulates angiogenic and lipolytic gene expression in human subcutaneous adipose tissue from exercise trained and untrained adults	Ludzki AC et al.	Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme	2022	Clinical Trial
Pharmacokinetic and pharmacodynamic equivalence of Biocon's biosimilar Insulin 70/30 with US-licensed HUMULIN® 70/30 formulation in healthy subjects: Results from the RHINE-3 (Recombinant Human INsulin Equivalence-3) study	Plum-Mörschel L et al.	Diabetes, obesity & metabolism	2022	Randomized Controlled Trial
A randomized pharmacokinetic and pharmacodynamic trial of two regular human insulins demonstrates bioequivalence in type 1 diabetes and availability of biosimilar insulin may improve access to this medication	Vencio S et al.	Diabetes, obesity & metabolism	2022	Randomized Controlled Trial
Early Postoperative Basal Insulin Therapy versus Standard of Care for the Prevention of Diabetes Mellitus after Kidney Transplantation: A Multicenter Randomized Trial	Schwaiger E et al.	Journal of the American Society of Nephrology : JASN	2021	Randomized Controlled Trial
Detemir vs neutral protamine Hagedorn insulin for diabetes mellitus in pregnancy: a comparative effectiveness, randomized controlled trial	Fishel Bartal M et al.	American journal of obstetrics and gynecology	2021	Randomized Controlled Trial
Advancing therapy with iGlarLixi versus premix BIAsp 30 in basal insulin-treated type 2 diabetes: Design and baseline characteristics of the SoliMix randomized controlled trial	McCrimmon RJ et al.	Diabetes, obesity & metabolism	2021	Clinical Study
Composite cardiovascular risk and BMI affected comparative profiles of BIAsp 30 + metformin vs BIAsp 30 monotherapy: a MERIT post-hoc analysis	Guo L et al.	Scientific reports	2021	Randomized Controlled Trial
Effects of Exenatide and Humalog Mix25 on Fat Distribution, Insulin Sensitivity, and β-Cell Function in Normal BMI Patients with Type 2 Diabetes and Visceral Adiposity	Wang X et al.	Journal of diabetes research	2020	Randomized Controlled Trial
Study rationale and design of the EANITIATE study (EmpAgliflozin compared to NPH Insulin for sTeroId diAbeTEs) - a randomized, controlled, multicenter trial of safety and efficacy of treatment with empagliflozin compared with NPH-insulin in patients with newly onset diabetes following initiation of glucocorticoid treatment	Klarskov CK et al.	BMC endocrine disorders	2020	Clinical Study
Biphasic human insulin 30 thrice daily, is it reasonable?	Saadeh NA et al.	BMC research notes	2020	Observational Study
Switching from Neutral Protamine Hagedorn Insulin to Insulin Glargine 300 U/mL Improves Glycaemic Control and Reduces Hypoglycaemia Risk: Results of a Multicentre, Prospective, Observational Study	Wolnik B et al.	Journal of diabetes research	2020	Observational Study
Comparing the efficacy and safety of insulin detemir versus neutral protamine hagedorn insulin in treatment of diabetes during pregnancy: a randomized, controlled study	Ji J et al.	BMJ open diabetes research & care	2020	Randomized Controlled Trial
Sexual Differences in response to Mid- or Low-Premixed Insulin Analogue in Patients with Type 2 Diabetes	Liu BL et al.	Journal of diabetes research	2020	Randomized Controlled Trial
Comparison of Hypoglycemia and Safety Outcomes With Long-Acting Insulins Versus Insulin NPH in Pregestational and Gestational Diabetes	Sleeman A et al.	The Annals of pharmacotherapy	2020	Observational Study
Comparison between the effect of regular human insulin and NPH with novo-rapid and levemir insulin in glycemic control in gestational diabetes	Amini FG et al.	Human antibodies	2019	Randomized Controlled Trial
Comparison of analog insulin mix 50:50 with human insulin mix 30:70 in persons with type 2 diabetes during Ramadan	Hajjaji IM et al.	International journal of clinical practice	2019	Randomized Controlled Trial
Efficacy and safety of three-times-daily versus twice-daily biphasic insulin aspart 30 in patients with type 2 diabetes mellitus inadequately controlled with basal insulin combined with oral antidiabetic drugs	Yang W et al.	Diabetes research and clinical practice	2019	Randomized Controlled Trial

More cited research

A 26-week, randomized trial of insulin detemir versus NPH insulin in children and adolescents with type 2 diabetes (iDEAt2) (None, human RCT)
A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as add-on therapy to oral glucose-lowering drugs in insulin-na (None, human RCT)
A comparison of semisynthetic human NPH insulin and porcine NPH insulin in the treatment of insulin-dependent diabetes mellitus (None, human trial (non-randomized))
A comparison of the pharmacokinetics and metabolic effects of human regular and NPH insulin mixtures (None, human RCT)

Conditions researched

Related compounds

FAQ

What is NPH Insulin (isophane)?

An intermediate-acting insulin made by combining insulin with protamine; also called isophane or NPH insulin (Humulin N, Novolin N).

How many registered human trials study NPH Insulin (isophane)?

The PeptideWhiz trial index lists 103 registered trials for NPH Insulin (isophane), the most recent from 2026.

How much published research exists on NPH Insulin (isophane)?

The PeptideWhiz paper index links 409 PubMed papers to NPH Insulin (isophane); by study type, 464 human and 1 animal studies.

Which conditions is NPH Insulin (isophane) researched for?

Atherosclerosis, cardiovascular disease & high blood pressure, Carpal tunnel, Chronic and systemic inflammation, Concussion, traumatic brain injury & stroke recovery, Dementia, Alzheimer's & cognitive decline, Diabetic retinopathy and glaucoma, Fat loss, obesity & body recomposition, Heart repair: after heart attack, heart failure & enlarged heart, High cholesterol and statins, Insulin resistance, prediabetes & type 2 diabetes, Kidney protection (CKD, diabetic kidney, lupus kidney), Lung health, asthma & COPD, Osteoarthritis, cartilage loss & avoiding joint replacement, Post-surgical inflammation and surgery recovery, Pregnancy and breastfeeding: safety notes.

Research and education only. Not medical advice. No dosing guidance. Data: ClinicalTrials.gov registry and PubMed via the PeptideWhiz index (204,289 studies).