Ulrike Hövelmann

Profil · Project Development

Aims: Severe hypoglycaemia (SH) remains common in type 1 diabetes (T1D). SH can be treated with glucagon, but its cost, short shelf life and difficulty of preparation and administration make glucagon underused. Dasiglucagon is a glucagon analogue available in a ready-to-use aqueous formulation. This is an integrated analysis of the safety and effi...

Background and Objective Individuals with diabetes mellitus may prefer different body regions for subcutaneous insulin administration. This trial investigated whether choice of injection region affects exposure and glucose-lowering effect of once-weekly basal insulin icodec.Methods In a randomised, open-label, crossover trial, 25 individuals with t...

Congenital hyperinsulinism (HI) is the most common cause of persistent hypoglycemia in neonates, infants, and children, and is caused by genetic mutations in the insulin secretion pathway in pancreatic beta-cells. Current medical and surgical treatments are often highly burdensome, only partially effective, and associated with significant morbidity...

Dapiglutide is a first-in-class peptide with dual activity on the GLP-1 and GLP-2 receptors and with potential to treat several metabolic/gastrointestinal (GI) diseases. In a multiple ascending dose cohort trial, 40 healthy subjects (mean BMI 24.6 kg/m2) received once weekly s.c. injections of dapiglutide (1, 2.25, 3.5 or 6 mg) or placebo for 4 wee...

People with diabetes may inject s.c. insulin in different body regions. To address if choice of injection region affects insulin icodec exposure and glucose-lowering effect, this study compared icodec administration in different s.c. injection regions. In a randomized, open-label, three-period crossover trial, 25 individuals with T2D on basal insul...

Glycine and cysteine are non-essential amino acids that are required to generate glutathione, an intracellular tripeptide that neutralizes reactive oxygen species and prevents tissue damage. During aging glutathione demand is thought to increase, but whether additional dietary intake of glycine and cysteine contributes towards the generation of glu...

Aims: The glucagon-like peptide-1 analogue, semaglutide, has been co-formulated with the absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate, for oral administration. This trial investigated whether upper gastrointestinal (GI) disease had any effect on the exposure of oral semaglutide, an important consideration given that its abs...

Aim: To evaluate the pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence (BE) of MYL-1601D biosimilar with originator, NovoLog® (Ref-InsAsp-US) and NovoRapid® (Ref-InsAsp-EU). Materials and methods: This was a double-blind, randomized, crossover study that enrolled 71 healthy subjects to receive a single subcutaneous dose (0.2 U/kg) of...

OBJECTIVE To evaluate the efficacy and safety of dasiglucagon, a ready-to-use, next-generation glucagon analog in aqueous formulation for subcutaneous dosing, for treatment of severe hypoglycemia in adults with type 1 diabetes. RESEARCH DESIGN AND METHODS This randomized, double-blind trial included 170 adult participants with type 1 diabetes, eac...

IntroductionMany commercially available glucagon products for treatment of severe hypoglycaemia require cumbersome reconstitution and potentially intimidating injection during an emergency. Nasal glucagon (NG) is a novel drug-device combination product consisting of a single-use dosing device that delivers glucagon dry powder through nasal administ...

Insulin icodec* is a novel basal insulin analog designed for single once-weekly (OW) subcutaneous injection. This randomized, double–blind, double–dummy trial investigated the pharmacokinetics (PK), pharmacodynamics (PD) and safety of insulin icodec. Fifty individuals with type 2 diabetes (insulin treated±metformin; 43 men; mean±SD age 57±5 years,...

Background Ultra rapid lispro (URLi) is a novel insulin lispro formulation developed to more closely match physiological insulin secretion and improve postprandial glucose control. This study compared the pharmacokinetics, glucodynamics, safety, and tolerability of URLi and Humalog® in patients with type 1 diabetes mellitus (T1DM).Methods This was...

URLi is a novel prandial insulin lispro formulation developed to more closely match physiological insulin secretion. This randomized, double-blind, 2 period, crossover, 10 h euglycemic clamp study assessed PK and glucodynamics after one 15U SC dose of URLi and lispro in 41 patients with T1D (mean ± SD age, 32.0 ± 6.8 y; duration of T1D, 17.7 ± 9.3...

Introduction: Severe hypoglycemia is one of the most feared adverse outcomes of insulin therapy and requires urgent assistance. The use of currently available glucagon products for rescue treatment of severe hypoglycemia is limited by complex reconstitution steps required before injection, as these products are not stable in solution. As a result,...

The GLP-1 analog semaglutide has been co-formulated with the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC) to allow oral administration. Since oral semaglutide is absorbed in the stomach, the effect of upper gastrointestinal disease (UGD) on exposure to oral semaglutide has been investigated in an open-label, parallel-g...

OBJECTIVE Currently available glucagon formulations have limited stability which hampers their use in dual‐hormone‐artificial pancreas‐systems. We characterized the pharmacokinetic and pharmacodynamic properties of dasiglucagon†, a novel, stable and liquid formulated glucagon‐analogue, during hypoglycaemic and euglycaemic conditions in adult patien...

Nasal Glucagon: Potentially Viable Alternative to Treat Insulin- Induced Hypoglycemia in Adults with Type 1 Diabetes JEFFREY SUICO, ULRIKE HÖVELMANN, SHUYU ZHANG, TONG SHEN, BRANDON BERGMAN, JENNIFER SHERR, ERIC ZIJLSTRA, BRIAN FRIER, LEONA PLUM-MORSCHEL Indianapolis, Indiana, USA Mainz, Germany Edinburgh, UK Commercially available glucagon require...

To develop a dual hormone artificial pancreas (DHAP) a liquid stable glucagon component is needed. Currently available glucagon products have limited stability after reconstitution and are therefore not suited for DHAP usage. Dasiglucagon is a novel liquid stable glucagon analog, which does not require mixing prior to use. In this randomized double...

URLi (LY900014), a novel ultra-rapid mealtime insulin in Phase 3 development, is shown to reduce postprandial glucose after subcutaneous injection. This study evaluated the pharmacokinetics and pharmacodynamics (PD) of URLi via CSII. In a double-blind, randomized cross-over study, 24 adult patients with T1D received URLi or insulin lispro (Humalog®...

Objective: Treatment of severe hypoglycemia outside of the hospital setting is limited to glucagon formulations requiring reconstitution before use, which may lead to erroneous or delayed glucagon administration. We compared the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics and safety and tolerability of different doses of dasigluc...

Background: Fast-acting insulin aspart (faster aspart) is insulin aspart set in a new formulation with faster initial absorption after subcutaneous administration. This study investigated the pharmacokinetic properties, including the absolute bioavailability, of faster aspart when administered subcutaneously in the abdomen, upper arm or thigh. Me...

Background Absorption of current rapid-acting insulins is too slow for patients with diabetes mellitus to achieve optimal postprandial glucose control. Faster-acting insulin aspart (faster aspart) is insulin aspart in a new formulation with faster early absorption. We compared the pharmacokinetic/pharmacodynamic properties of faster aspart and insu...

Background Due to population aging, an increasing number of elderly patients with diabetes use insulin. It is therefore important to investigate the characteristics of new insulins in this population. Faster-acting insulin aspart (faster aspart) is insulin aspart (IAsp) in a new formulation with faster absorption. This study investigated the pharma...

Aims: Basal insulin peglispro (BIL) is a novel PEGylated basal insulin with a flat pharmacokinetic and glucodynamic profile and reduced peripheral effects, which results in a hepato-preferential action. In Phase 3 trials, patients with T1DM treated with BIL had lower prandial insulin requirements, yet improved prandial glucose control, relative to...

Objective: Lipohypertrophy (LHT) is common in insulin-treated patients but its exact impact on insulin absorption and action is unclear. Research design and methods: In this crossover study, 13 patients with type 1 diabetes received subcutaneous abdominal injections of 0.15 units/kg insulin lispro into LHT (confirmed by examination and ultrasoun...

Faster aspart ist eine neue Insulin aspart (IAsp) Formulierung mit schnellerer initialer Resorption nach subkutaner Injektion. In dieser doppelblinden Crossover-Studie wurden Pharmakokinetik und Pharmakodynamik (PK/PD) einer Einzelgabe (0,2 E/kg Faster aspart bzw. IAsp) bei 30 alteren (≥65 Jahre) und 37 jungeren Patienten (18 – 35 Jahre) mit T1D ve...

A medical need remains for a once-daily insulin with 24-h basal coverage in all patients. We characterize the steady-state (SS) pharmacokinetic/pharmacodynamic properties of insulin degludec (IDeg) versus insulin glargine (IGlar). In this controlled, single-center study, 66 type 1 diabetes patients were randomized to two 8-day periods of once-daily...

AimsFaster-acting insulin aspart (faster aspart) is a new formulation of insulin aspart, containing excipients resulting in faster absorption after s.c. injection. This randomised, single-centre, double-blind study evaluated pharmacokinetics and pharmacodynamics of faster aspart and insulin aspart.Materials and Methods Fifty-two patients with T1D (...

This study assessed pharmacokinetics (PK) and pharmacodynamic postprandial glycemia (PPG) in patients with type 1 diabetes mellitus (T1DM) after a standardized liquid meal following insulin lispro (IL) or regular human insulin (RHI) given by microneedle-based intradermal (ID) versus subcutaneous (SC) delivery. In this randomized, open-label, five-w...

Because of its zinc-free formulation insulin glulisine (GLU) might have a faster onset of action than other short-acting analogues. We compared the pharmacokinetics and pharmacodynamics of GLU with those of insulin aspart (ASP). Twelve healthy subjects, aged 18-65 years, participated in this randomized, double-blind, crossover trial. Subjects recei...

Exercise is associated with an increased risk of hypoglycemic or hyperglycemic events. The aim of this study was to assess glucose changes during and after physical exercise in patients with type 1 diabetes managed by continuous subcutaneous insulin infusion before and after a 14-day moderate or intense exercise program. Sixteen male patients [hemo...

OBJECTIVE Pharmacological profiles of biphasic insulin aspart 30/70 (BIAsp 30) once daily (OD), twice daily (b.i.d.), and three times daily (t.i.d.) were compared with other insulin regimens in two crossover glucose clamp studies of insulin-treated type 2 diabetic patients. RESEARCH DESIGNS AND METHODS Study 1 consisted of BIAsp 30 OD, b.i.d., and...