Insulin Efsitora versus Degludec in Type 2 Diabetes without Previous Insulin Treatment.

Background: Insulin efsitora alfa (efsitora) is a new basal insulin designed for once-weekly administration. Data on safety and efficacy have been limited to small, phase 1 or phase 2 trials.

Methods: We conducted a 52-week, phase 3, parallel-design, open-label, treat-to-target trial involving adults with type 2 diabetes who had not previously received insulin.

Novel Once-Weekly Basal Insulin Fc Achieved Similar Glycemic Control With a Safety Profile Comparable to Insulin Degludec in Patients With Type 1 Diabetes.

Objective: Basal Insulin Fc (BIF; insulin efsitora alfa; LY3209590), a fusion protein combining a novel single-chain insulin variant with a human IgG Fc domain, is designed for once-weekly basal insulin administration. This phase 2 study assessed safety and efficacy of BIF versus degludec in 265 patients with type 1 diabetes (T1D) using multiple daily injections.

Research Design And Methods: During this randomized, parallel, open-label study, patients with T1D were randomized (1:1) to receive BIF once weekly or degludec once daily over the 26-week treatment period.

Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial.

Importance: The effects of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, as an addition to insulin glargine for treatment of type 2 diabetes have not been described.

Objective: To assess the efficacy and safety of tirzepatide added to insulin glargine in patients with type 2 diabetes with inadequate glycemic control.

Design, Setting, And Participants: Randomized phase 3 clinical trial conducted at 45 medical research centers and hospitals in 8 countries (enrollment from August 30, 2019, to March 20, 2020; follow-up completed January 13, 2021) in 475 adults with type 2 diabetes and inadequate glycemic control while treated with once-daily insulin glargine with or without metformin.

Immunogenicity of the Novel Glucagon Analogue Dasiglucagon: Results of a Dedicated Immunogenicity Trial in Type 1 Diabetes.

Dasiglucagon is a next-generation glucagon analogue that is stable in aqueous formulation. This dedicated immunogenicity trial to support use as rescue treatment for severe hypoglycemia was conducted to evaluate the immunogenicity of repeated subcutaneous doses of dasiglucagon in subjects with type 1 diabetes. A total of 112 subjects were randomized 1:1 to receive three subcutaneous weekly doses of either 0.

Long-Term Efficacy and Safety of Ultra Rapid Lispro (URLi) in Adults with Type 1 Diabetes: The PRONTO-T1D Extension.

Introduction: The PRONTO-T1D study, which evaluated the efficacy and safety of ultra rapid lispro (URLi) versus lispro in adults with type 1 diabetes (T1D), met the primary endpoint of noninferiority of HbA1c change from baseline compared to lispro at 26 weeks. We present results of an additional 26-week treatment phase evaluating long-term efficacy and safety of URLi.

Methods: In this phase 3, treat-to-target study, subjects were randomized to double-blind mealtime URLi, lispro, or open-label postmeal URLi with insulin degludec or glargine for 26 weeks.

Ultra rapid lispro improves postprandial glucose control compared with lispro in patients with type 1 diabetes: Results from the 26-week PRONTO-T1D study.

Aims: To evaluate the efficacy and safety of ultra rapid lispro (URLi) versus lispro in adults with type 1 diabetes in a 26-week, treat-to-target, phase 3 trial.

Materials And Methods: After an 8-week lead-in to optimize basal insulin glargine or degludec, patients were randomized to double-blind mealtime URLi (n = 451) or lispro (n = 442), or open-label post-meal URLi (n = 329). The primary endpoint was change from baseline glycated haemoglobin (HbA1c) to 26 weeks (non-inferiority margin 0.

Increased insulin clearance in peroxisome proliferator-activated receptor gamma2 Pro12Ala.

The Pro12Ala polymorphism of the peroxisome proliferator-activated receptor (PPARgamma(2)) is associated with reduced risk for type 2 diabetes. Although increased insulin sensitivity of glucose disposal and lipolysis has been reported, the exact mechanism by which the risk reduction is conferred is not clear. Because the conclusion of greater insulin sensitivity hinged upon lower insulin levels in some studies, it is possible that more efficient insulin clearance is involved.

Intramyocellular lipids: anthropometric determinants and relationships with maximal aerobic capacity and insulin sensitivity.

The existence of metabolically relevant intramyocellular lipids (IMCL) as assessed by the noninvasive (1)H-magnetic resonance spectroscopy (MRS) has been established. In the present studies, we analyzed the relationships between IMCL in two muscle types [the predominantly nonoxidative tibialis muscle (tib) and the predominantly oxidative soleus muscle (sol)] and anthropometric data, aerobic capacity (VO(2)max, bicycle ergometry, n = 77) and insulin sensitivity (hyperinsulinemic euglycemic clamp, n = 105) using regression analysis. In univariate regression, IMCL (tib) was weakly but significantly correlated with percentage of body fat (r = 0.

Lipid content in the musculature of the lower leg assessed by fat selective MRI: intra- and interindividual differences and correlation with anthropometric and metabolic data.

Purpose: To assess the muscular lipid content (LC) in different muscle groups of the lower leg by a magnetic resonance imaging technique working with chemical shift selective excitation, and comparison with anthropometric and metabolic data.

Materials And Methods: Examinations were performed in 67 volunteers (54 male/13 female, age 29 +/- seven years) on a 1.5 T whole body imager, applying a highly selective spectral-spatial technique for fat selective MRI.

Effect of glimepiride on insulin-stimulated glycogen synthesis in cultured human skeletal muscle cells: a comparison to glibenclamide.

Objective: To examine the effect of glimepiride on insulin-stimulated glycogen synthesis in cultured human skeletal muscle cells in comparison with glibenclamide.

Research Design And Methods: Myotubes derived from glucose-tolerant subjects were incubated with glimepiride or glibenclamide (0-100 micro mol/l) for 4 h and with or without insulin (100 nmol/l) for 2 h, and subsequently glycogen synthesis was determined.

Results: Glimepiride had no significant effect on basal glycogen synthesis; in contrast, glimepiride caused a dose-dependent increase of insulin-stimulated glycogen synthesis, with a maximal effect of 39.