This retrospective cohort study compared real‐world clinical and healthcare‐resource utilization (HCRU) data in patients with type 2 diabetes using basal insulin (BI) who switched to insulin glargine 300 units/mL (Gla‐300) or another BI. Data from the Predictive Health Intelligence Environment database 12 months before (baseline) and 6 months after (follow‐up) the switch date (index date, March 1, 2015 to May 31, 2016) included glycated haemoglobin A1c (HbA1c), hypoglycaemia, HCRU and associated costs. Baseline characteristics were balanced using propensity score matching. Change in HbA1c from baseline was similar in both matched cohorts (n = 1819 in each). Hypoglycaemia incidence and adjusted event rate were significantly lower with Gla‐300. Patients switching to Gla‐300 had a significantly lower incidence of HCRU related to hypoglycaemia. All‐cause and diabetes‐related hospitalization and emergency‐department HCRU were also favourable for Gla‐300. Lower HCRU translated to lower costs in patients using Gla‐300. In this real‐world study, switching to Gla‐300 reduced the risk of hypoglycaemia in patients with type 2 diabetes when compared with those switching to another BI, resulting in less HCRU and potential savings of associated costs.

Pioglitazone in combination with insulin therapy improved glycaemic control, reduced insulin dose requirements and improved lipid profiles in patients with type 2 diabetes previously poorly controlled with combination therapy.

Protein tyrosine phosphatase 1B (PTP1B) is a protein tyrosine phosphatase of unknown function, although increasing evidence supports a role for this phosphatase in insulin action. We have investigated the interaction of PTP1B with the insulin receptor using a PTP1B glutathione S-transferase (GST) fusion protein with a point mutation in the enzyme's catalytic domain. This fusion protein is catalytically inactive, but the phosphatase's phosphotyrosine binding site is maintained. The activated insulin receptor was precipitated from purified receptor preparations and whole-cell lysates by the inactive PTP1B-GST, demonstrating a direct association between the insulin receptor and PTP1B. A p120 of unknown identity was also precipitated from whole-cell lysates by the PTP1B fusion protein, but IRS-1 (pp185) was not. A catalytically inactive [35S]PTP1B-fusion protein bound directly to immobilized insulin receptor kinase domains and was displaced in a concentration-dependent manner. Finally, tyrosine-phosphorylated PTP1B was precipitated from whole-cell lysates by an anti-insulin receptor antibody after insulin stimulation. The site of interaction between PTP1B and the insulin receptor was studied using phosphopeptides modeled after the receptor's kinase domain, the NPXY domain, and the COOH-terminal. Each phosphopeptide inhibited the PTP1B-GST:insulin receptor interaction. Study of mutant insulin receptors demonstrated that activation of the kinase domain is necessary for the PTP1B:insulin receptor interaction, but receptors with deletion of the NPXY domain or of the COOH-terminal can still bind to the PTP1B-GST. We conclude that PTP1B can associate directly with the activated insulin receptor at multiple different phosphotyrosine sites and that dephosphorylation by PTP1B may play a significant role in insulin receptor signal transduction.

Aims To compare HbA1c and hypoglycaemia in insulin‐naïve patients with type 2 diabetes (T2D) who initiated insulin glargine 300 units/mL (Gla‐300) or 100 units/mL (Gla‐100). Materials and methods This retrospective cohort study examined electronic medical records of insulin‐naïve adults with T2D who initiated Gla‐300 or Gla‐100 during March 2015 through to December 2016 with active records for ≥12 months before and ≥6 months after initiation, and ≥1 valid HbA1c value during 6‐month baseline and 90–180‐day follow‐up. Outcomes included HbA1c and hypoglycaemia. Cohorts were propensity score‐matched (1:2) on baseline demographic and clinical characteristics. Sensitivity analyses were conducted using broader inclusion criteria. Results The matched cohorts included 1004 Gla‐300 and 2008 Gla‐100 initiators (mean age 60.4 years; 53.2% male). During 6‐month follow‐up, Gla‐300 versus Gla‐100 initiators had a greater mean HbA1c decrease (−1.52 ± 2.08% vs. –1.30 ± 2.12%; P = 0.003) and more patients achieved HbA1c <7% (25.0% vs. 21.5%; P = 0.029) and <8% (55.0% vs. 49.2%; P = 0.002); and HbA1c <7% (21.9% vs. 17.4%; P = 0.003) and <8% (49.1% vs. 41.8%; P < 0.001) without hypoglycaemia. Gla‐300 initiators were similarly or less likely to have any or inpatient/emergency department‐associated hypoglycaemia during 3‐ and 6‐month follow‐up (e.g. any hypoglycaemia to 6 months: 9.7% vs. 12.5%; adjusted odds ratio 0.61; P = 0.057). Conclusions Among insulin‐naïve adults with T2D, Gla‐300 was associated with significantly better HbA1c reductions (latest value during 90–180‐day follow‐up) and similar or improved hypoglycaemia outcomes (3‐ and 6‐month follow‐up) than Gla‐100.

Aim To compare the second‐generation basal insulin glargine 300 units/mL (Gla‐300) and first‐generation basal insulins on glycaemic control and hypoglycaemia risk in older adults with type 2 diabetes (T2D). Materials and methods DELIVER 3 was a retrospective observational cohort study of electronic medical records. A total of 1176 older adults (aged ≥ 65 years) with T2D and ≥1 HbA1c value during 6 month baseline and 3 to 6 month follow‐up who switched from basal insulin to Gla‐300 were propensity score‐matched to 1176 older adults who switched to a first‐generation basal insulin [insulin detemir (IDet) or insulin glargine 100 units/mL (Gla‐100)]. Outcomes were follow‐up HbA1c, achievement of HbA1c <7% and <8%, hypoglycaemia incidence and event rates, and healthcare resource utilization. Results Following basal insulin switching, HbA1c reductions were greater/similar with Gla‐300 versus IDet/Gla‐100 (variable follow‐up: −0.45% ± 1.40% vs. −0.29% ± 1.57%; P = .021; fixed follow‐up: −0.48% ± 1.49% vs. −0.38% ± 1.59%; P = .114), while HbA1c goal attainment was similar in both cohorts. Gla‐300 was associated with less hypoglycaemia [event rate: adjusted rate ratio (aRR): 0.63, 95% CI: 0.53‐0.75; P < .001] and inpatient/emergency department‐associated hypoglycaemia (adjusted hazard ratio: 0.58, 95% CI: 0.37‐0.90; P = .016; aRR: 0.43, 95% CI: 0.31‐0.60; P < .001) by variable follow‐up. By fixed follow‐up, hypoglycaemia results significantly or numerically favoured Gla‐300. Conclusion Among older adults with T2D, switching to Gla‐300 versus Gla‐100/IDet was associated with greater/similar improvements in glycaemic control, and generally less hypoglycaemia.