To examine the effect of dapagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on major components renal glucose reabsorption (decreased maximum reabsorptive capacity [TmG], increased splay, and reduced threshold), using pancreatic/stepped hyperglycemic clamp (SHC) technique.Subjects with type diabetes (n=12) matched healthy subjects underwent pancreatic/SHC (plasma range 5.5-30.5 mmol/L) at baseline after 7 days dapagliflozin treatment. A pharmacodynamic model was developed to...

Aim: Canagliflozin is a sodium‐glucose co‐transporter 2 (SGLT2) inhibitor that being investigated for the treatment of type diabetes mellitus (T2DM). Methods: This was randomized, double‐blind, placebo‐controlled, parallel‐group, 28‐day study conducted at two sites, in 29 subjects with T2DM not optimally controlled on insulin and up to one oral antihyperglycaemic agent. Subjects were treated canagliflozin 100 mg QD or 300 twice daily (BID) placebo. Safety, tolerability, pharmacokinetic...

OBJECTIVE To determine the effects of volanesorsen (ISIS 304801), a second-generation 2'-O-methoxyethyl chimeric antisense inhibitor apolipoprotein (apo)C-III, on triglyceride (TG) levels and insulin resistance in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS A randomized, double-blind, placebo-controlled trial was performed 15 adult diabetes (HbA1c >7.5% [58 mmol/mol]) hypertriglyceridemia (TG >200 <500 mg/dL). Patients were randomized 2:1 to receive 300 mg...

Aims: Effects of the long acting GLP-1 analogue - liraglutide in subjects with type 2 diabetes. Methods: 144 diabetic on metformin treatment (1000 mg BID) were randomised to 5 weeks (double-blind) plus liraglutide, or metformin, glimepiride (open label). The dose was increased weekly from 0.5 OD. Results: Liraglutide added monotherapy associated a significant reduction fasting serum glucose (FSG) (-3.9 mM -4.9; -2.9) (primary objective), and HbA1c levels (-0.8% -1.2; -0.4). Furthermore,...

OBJECTIVE Human regular U-500 (U-500R) insulin (500 units/mL) is increasingly being used clinically, yet its pharmacokinetics (PK) and pharmacodynamics (PD) have not been well studied. Therefore, we compared PK PD of clinically relevant doses U-500R with the same human U-100 (U-100R) (100 units/mL). RESEARCH DESIGN AND METHODS This was a single-site, randomized, double-blind, crossover euglycemic clamp study. Single subcutaneous injections 50- 100-unit U-100R were administered to 24 healthy...

Aim To test the hypothesis that an improving body composition in insulin‐resistant individuals could enhance insulin sensitivity. Methods A total of 16 people with a mean mass index 29.3 kg/m 2 and resistance, received single dose bimagrumab or placebo were assessed at week 10 for sensitivity, using hyperinsulinaemic‐euglycaemic clamp intravenous glucose tolerance ( IVGTT ), dual energy X ‐ray absorptiometry positron‐emission tomography. Results Bimagrumab increased lean by 2.7% P < .05)...

Inhaled insulin (INH, Exubera) is under investigation for preprandial treatment of patients with type 1 and 2 diabetes (1–3). This dry-powder formulation delivered by aerosol, permitting the noninvasive administration rapid-acting (4). Preliminary studies have shown that INH provides reproducible effective control glycemia (1,5–7). randomized controlled trial examined extent to which availability affects perceived acceptability therapy among who failed achieve target on current...

Background: This study compared insulin lispro (IL) pharmacokinetics (PK) and pharmacodynamics (PD) delivered via microneedle intradermal (ID) injection with subcutaneous (SC) under euglycemic glucose clamp conditions. Methods: Ten healthy male volunteers were administered 10 international units (IU) of IL at 3 lengths (1.25, 1.50, or 1.75 mm) in a randomized, crossover fashion on Days 1–3 followed by repetitive ID 1.5-mm dose (Day 4) an SC 5). Results: Microneedle delivery resulted more...

To compare the pharmacokinetics and glucodynamics of three rapid-acting insulin analogs (aspart, glulisine, lispro) injected subcutaneously with or without recombinant human hyaluronidase (rHuPH20).This double-blind six-way crossover euglycemic glucose clamp study was conducted in 14 healthy volunteers. Each analog (0.15 units/kg) rHuPH20.The commercial formulations had comparable time-exposure time-action profiles as follows: 50% exposure at 123-131 min total infused 183-186 min. With...

To assess the therapeutic potential of fatty acid synthase (FASN) inhibition with FT-4101, a potent, selective, orally bioavailable, small-molecule by (a) evaluating dose-response single FT-4101 doses (3, 6 and 9 mg) on hepatic de novo lipogenesis (DNL) in healthy participants (Study 1) (b) demonstrating safety, tolerability efficacy steatosis after 12 weeks dosing patients non-alcoholic liver disease (NAFLD; Study 2).In 1, three sequential cohorts men (n = 10/cohort) were randomized to...

Abstract Context The effect of sotagliflozin (a dual sodium–glucose cotransporter [SGLT] 2 and SGLT1 inhibitor) on intestinal glucose absorption has not been investigated in humans. Objective To measure rate appearance oral (RaO) using a tracer method following standardized mixed meals taken after single or canagliflozin doses. Setting Clinical research organization Design participants In double-blind, 3-period crossover study (NCT01916863), 24 healthy were randomized to cohorts 12...

This study evaluates the pharmacodynamic and pharmacokinetic properties of novel ultra-fast insulin product VIAject, a formulation human soluble generally recognised as safe ingredients designed to increase rate absorption.We performed five euglycaemic glucose clamps (Biostator; target blood 5 mmol/l) in ten healthy volunteers. Using crossover design with fixed treatment order, 12 IU insulin, U lispro were injected s.c. abdominal region on three days. On other two days, 6 3...

To compare the pharmacokinetics, pharmacodynamics, and safety of insulin lispro or regular human (RHI) with without recombinant hyaluronidase (rHuPH20) administered before a standardized meal.In this four-way, crossover study, 22 patients type 1 diabetes received injections individually optimized doses RHI rHuPH20 liquid meal.With coadministration, early exposure (0-60 min) increased by 54% (P = 0.0011) for 206% < 0.0001) compared respective alone. Peak blood glucose decreased 26 mg/dL...

Remogliflozin etabonate (RE) is the prodrug of remogliflozin, a selective inhibitor renal sodium-dependent glucose transporter 2 (SGLT2), which could increase urine excretion (UGE) and lower plasma in humans. This double-blind, randomized, placebo-controlled, single-dose, dose-escalation, crossover study first human trial designed to evaluate safety, tolerability, pharmacokinetics (PK) pharmacodynamics RE. All subjects received single oral doses either RE or placebo separated by...

Various factors influence the pharmacokinetic and pharmacodynamic properties of insulin analogs. The aim present study was to determine time steady state degludec (IDeg), a basal analog with an ultralong duration action, after once-daily subcutaneous administration in subjects varying age, diabetes type, ethnicity.Time analyzed 195 across five Phase I randomized single-center double-blind studies: three type 1 (T1DM), including one elderly subjects, two 2 (T2DM), African American...

Aims We assessed safety and efficacy of two selective 11β‐HSD1 inhibitors (RO5093151/RO‐151 RO5027383/RO‐838) in this randomized, controlled study metformin‐treated patients with type 2 diabetes. Methods Patients either received placebo (N = 21), RO‐151 BID 5 mg 24) or 200 20) RO‐838 QD 50 21) for 28 days. Metabolic assessments comprising nine‐point plasma glucose profiles, oral tolerance tests determination metabolic biomarkers including insulin, C‐peptide, glucagon, HbA1c lipids were done...

OBJECTIVE Healthy pancreatic β-cells secrete the hormones insulin and amylin in a fixed ratio. Both are lacking type 1 diabetes, postprandial glucose control using therapy alone is difficult. This study tested pharmacodynamic effects of analog pramlintide delivered ratio over 24-h period. RESEARCH DESIGN AND METHODS Patients with diabetes were stabilized on pump lispro before randomized, single-masked, two-way crossover, inpatient which regular human was administered or placebo separate...

Activation of GPR119 receptors, expressed on enteroendocrine and pancreatic islet cells, augments glucagon counterregulatory responses to hypoglycemia in pre-clinical models. We hypothesized that MBX-2982, a agonist, would augment experimental participants with type 1 diabetes. To assess this, we designed phase 2a double-masked, cross-over trial 18 (20–60 years) Participants were randomized treatment 600 mg MBX-2982 or placebo daily for 14 days two-week washout between treatments....

&lt;p dir="ltr"&gt;Activation of GPR119 receptors, expressed on enteroendocrine and pancreatic islet cells, augments glucagon counterregulatory responses to hypoglycemia in pre-clinical models. We hypothesized that MBX-2982, a agonist, would augment experimental participants with type 1 diabetes.&lt;b&gt; &lt;/b&gt;To assess this, we designed phase 2a double-masked, cross-over trial 18 (20–60 years) diabetes. Participants were randomized treatment 600 mg MBX-2982 or placebo daily for 14 days...