Post Hoc Analysis Evaluating the Impact of Antihyperglycemic Background Therapies on Attainment of A1C Targets Without Hypoglycemia in the ACHIEVE Control Pragmatic, Real-Life Study.

BACKGROUND: ACHIEVE Control, a prospective, open-label, randomized, pragmatic, real-life study in insulin-naive people with type 2 diabetes (A1C 8.0-11.0%), demonstrated superiority of insulin glargine 300 units/mL (Gla-300) versus first-generation standard-of-care basal insulin (SOC-BI; glargine 100 units/mL or insulin detemir) in achieving individualized A1C targets without documented symptomatic (glucose ≤3.9 mmol/L [≤70 mg/dL] or <3.0 mmol/L [<54 mg/dL]) or severe hypoglycemia (American Diabetes Association level 3) at 6 months. Noninsulin antihyperglycemic background therapies are commonly used; however, sulfonylureas may increase hypoglycemia risk. This post hoc analysis assessed outcomes according to background therapy. METHODS: Subgroup analyses were performed per concomitant use/nonuse of sulfonylureas, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase 4 inhibitors, or sodium-glucose cotransporter 2 (SGLT2) inhibitors. End points (6 and 12 months) included A1C target attainment without documented symptomatic or severe hypoglycemia, A1C target attainment, and absence of documented symptomatic or severe hypoglycemia. RESULTS: Odds ratios (ORs) at 12 months mostly favored Gla-300 versus SOC-BI across subgroups except in analysis of SGLT2 inhibitors, in which ORs were similar. Among sulfonylurea users, ORs at 12 months strongly favored Gla-300 versus SOC-BI for all end points, particularly A1C target achievement without documented symptomatic hypoglycemia (glucose ≤3.9 mmol/L [≤70 mg/dL]; OR 1.25, 95% CI 1.02-1.53) or severe hypoglycemia and achievement of no documented symptomatic hypoglycemia (glucose <3.0 mmol/L [<54 mg/dL]; OR 1.25, 95% CI 1.02-1.52) or severe hypoglycemia. CONCLUSION: The results suggest that, in insulin-naive people with type 2 diabetes, Gla-300 is effective with a risk of hypoglycemia that is lower than or similar to that of SOC-BI regardless of background medication. Individuals receiving concomitant sulfonylureas were more likely to remain without symptomatic or severe hypoglycemia with Gla-300.

Target attainment in insulin-naive patients at high risk for hypoglycemia: Results from ACHIEVE Control.

AIMS: To better understand outcomes in people with type 2 diabetes at high risk of hypoglycemia, we conducted post hoc analyses in subgroups of participants from the real-world ACHIEVE Control study (NCT02451137) with ≥1 hypoglycemia risk factor. METHODS: Insulin-naive adults with type 2 diabetes and A1c ≥8% were randomized 1:1 to insulin glargine 300 U/mL (Gla-300) or standard-of-care basal insulin (SOC-BI). Participants had documented history of ≥1 risk factors for hypoglycemia: chronic kidney disease, cardiovascular disease, dementia or blindness, age ≥65 years, or history of hypoglycemia. Outcomes included individualized A1c target attainment without documented symptomatic hypoglycemia (blood glucose [BG] ≤3.9 mmol/L or <3.0 mmol/L) or severe hypoglycemia, A1c target attainment, and absence of documented symptomatic or severe hypoglycemia at 6 and 12 months. RESULTS: Within subgroups, odds ratios generally showed trends favoring Gla-300 versus SOC-BI, particularly for hypoglycemia avoidance in participants ≥65 years of age (BG ≤3.9 mmol/L; odds ratio, 1.52; 95% confidence interval, 1.14-2.03) and those with chronic kidney disease (BG ≤3.9 mmol/L; odds ratio, 2.28; 95% confidence interval, 1.26-4.12). Results were consistent with the overall population. CONCLUSIONS: These data suggest potential benefit of Gla-300 versus SOC-BI for avoiding hypoglycemia in participants with ≥1 hypoglycemia risk factor.

Bridging ß-Cyclodextrin Prevents Self-Inclusion, Promotes Supramolecular Polymerization, and Promotes Cooperative Interaction with Nucleic Acids.

A bridge to assemble: Cyclodextrins bridged with an ammonium linker bearing a hydrophobic substituent can efficiently form supramolecular polymers and avoid the competing self-inclusion and head-to-head processes. Furthermore, the self-assembling cyclodextrin derivative interacts in a highly cooperative manner with DNA, as demonstrated by compaction experiments. It also interacts cooperatively with siRNA and allows its transfection.

Discovery of Novel (Imidazo[1,2-a]pyrazin-6-yl)ureas as Antiproliferative Agents Targeting P53 in Non-small Cell Lung Cancer Cell Lines.

A series of (imidazo[1,2-a]pyrazin-6-yl)ureas were synthesized through 6-aminoimidazo[1,2-a]pyrazine as a key intermediate. 1-(Imidazo[1,2-a]pyrazin-6-yl)-3-(4-methoxy - phenyl)urea displayed a cytostatic activity against a non-small cell lung cancer cell line and was chosen for further mechanistic studies. Growth kinetics highlighted a selective dose-dependent response of P53-mutant NSCLC-N6-L16 cell line and overexpression of TP53 gene induced by this compound. These pharmacological data suggest a promising reactivation of p53 mutant in NSCLC-N6-L16 cell line.