Real-world community hospital hyperglycemia management in noncritically ill, type 2 diabetic patients: a comparison between basal-bolus insulin and correctional insulin.

Purpose: This study evaluated the safety and efficacy of two insulin regimens for inpatient hyperglycemia management: combination short-plus long-acting insulin (basal-bolus insulin regimen, BBIR) vs. short-acting insulin only (correctional insulin only regimen, CIOR). Methods: Chart reviews identified noncritically ill patients with pre-existing type 2 diabetes mellitus receiving insulin injections. Study participants (N = 138) were divided into BBIR (N = 104) and CIOR (N = 34) groups. Data for the entire duration of each patient's stay were analyzed. Results: The primary outcome of percent hyperglycemic days was higher in BBIR vs. CIOR (3.97 ± 0.33% vs. 1.22 ± 0.38%). The safety outcome of percent hypoglycemic events was not different between BBIR and CIOR (0.78 ± 0.22% vs. 0.53 ± 0.37%). Regarding secondary outcomes, the percentage of euglycemic days was lower in BBIR vs. CIOR (26.74 ± 2.97% vs. 40.98 ± 5.91%). Overall blood glucose (BG) and daily insulin dose were higher in BBIR vs. CIOR (231.43 ± 5.37 vs. 195.55 ± 6.25 mg/dL and 41.36 ± 3.07 vs. 5.02 ± 0.68 units, respectively). Insulin regimen-associated differences in hyperglycemia and daily insulin dose persisted after adjusting for covariates. Conclusion: Our observations linking BBIR to worse glycemic outcomes differ from those reported in the randomized controlled Rabbit 2 and Rabbit 2 Surgery trials. This discrepancy can be partly explained by the fact that BBIR patients displayed worse glycemic baselines. Also, there was no diabetes stewardship team to monitor BG and modify insulin therapy, which is relevant since achieving euglycemia in BBIR patients requires more dose adjustments. This study highlights challenges with standard inpatient glycemic management and calls for further research assessing the benefits of pharmacist-led diabetes stewardship.

Pharmacokinetic and pharmacodynamic equivalence of Biocon's biosimilar Insulin 70/30 with US-licensed HUMULIN® 70/30 formulation in healthy subjects: Results from the RHINE-3 (Recombinant Human INsulin Equivalence-3) study.

AIM: To establish the pharmacokinetic (PK) and pharmacodynamic (PD) equivalence of proposed biosimilar insulin 70/30 (Biocon's Insulin-70/30) and HUMULIN® 70/30 (HUMULIN-70/30; Eli Lilly and Company, IN). MATERIALS AND METHODS: In this phase 1, automated euglycaemic glucose clamp study, 78 healthy subjects were randomized (1:1) to receive a single dose of 0.4 IU/kg of Biocon's Insulin-70/30 and HUMULIN-70/30. Plasma insulin concentrations and glucose infusion rates (GIRs) were assessed over 24 hours. Primary PK endpoints were area under the insulin concentration-time curve from 0 to 24 hours - AUCins.0-24h - and maximum insulin concentration - Cins.max . Primary PD endpoints were area under the GIR time curve from 0 to 24 hours - AUCGIR.0-24h - and maximum GIR - GIRmax . RESULTS: Equivalence was shown between Biocon's Insulin-70/30 and HUMULIN-70/30 for the primary PK/PD endpoints. The 90% confidence intervals of the treatment ratios were entirely within the acceptance range of 80.00%-125.00%. The secondary PK/PD profiles were also comparable. There were no clinically relevant differences in the safety profiles of the two treatments and no serious adverse events were reported. CONCLUSION: PK/PD equivalence was demonstrated between Biocon's Insulin-70/30 and HUMULIN-70/30 in healthy subjects. Treatment with Biocon's Insulin-70/30 and HUMULIN-70/30 was well tolerated.

Comparative Efficacy and Safety of Ultra-Long-Acting, Long-Acting, Intermediate-Acting, and Biosimilar Insulins for Type 1 Diabetes Mellitus: a Systematic Review and Network Meta-Analysis.

BACKGROUND: Increasing availability of competing biosimilar alternatives makes it challenging to make treatment decisions. The purpose of this review is to evaluate the comparative efficacy and safety of ultra-long-/long-/intermediate-acting insulin products and biosimilar insulin compared to human/animal insulin in adults with type 1 diabetes mellitus (T1DM). METHODS: MEDLINE, EMBASE, CENTRAL, and grey literature were searched from inception to March 27, 2019. Randomized controlled trials (RCTs), quasi-experimental studies, and cohort studies of adults with T1DM receiving ultra-long-/long-/intermediate-acting insulin, compared to each other, as well as biosimilar insulin compared to human/animal insulin were eligible for inclusion. Two reviewers independently screened studies, abstracted data, and appraised risk-of-bias. Pairwise meta-analyses and network meta-analyses (NMA) were conducted. Summary effect measures were mean differences (MD) and odds ratios (OR). RESULTS: We included 65 unique studies examining 14,200 patients with T1DM. Both ultra-long-acting and long-acting insulin were superior to intermediate-acting insulin in reducing A1c, FPG, weight gain, and the incidence of major, serious, or nocturnal hypoglycemia. For fasting blood glucose, long-acting once a day (od) was superior to long-acting twice a day (bid) (MD - 0.44, 95% CI: - 0.81 to - 0.06) and ultra-long-acting od was superior to long-acting bid (MD - 0.73, 95% CI - 1.36 to - 0.11). For weight change, long-acting od was inferior to long-acting bid (MD 0.58, 95% CI: 0.05 to 1.10) and long-acting bid was superior to long-action biosimilar od (MD - 0.90, 95% CI: - 1.67 to - 0.12). CONCLUSIONS: Our results can be used to tailor insulin treatment according to the desired results of patients and clinicians and inform strategies to establish a competitive clinical market, address systemic barriers, expand the pool of potential suppliers, and favor insulin price reduction. PROSPERO REGISTRATION: CRD42017077051.

Effects of Recommendations for Diabetes Management at Hospital Discharge on Long-Term Diabetes Control.

OBJECTIVE: To determine the impact of diabetes-specific recommendations at 1 year after hospital discharge on glycemic control and diabetes care in an outpatient setting. METHODS: A total of 139 patients with type 2 diabetes on a basal-bolus insulin regimen during hospitalization were included in the statistical analysis. We gathered data on treatment regimens after 12 to 16, 26 to 30, and 52 to 56 weeks following discharge as well as glycosylated hemoglobin (HbA1c) levels for all patients. Prescriptions for diabetes therapy were retrieved. All changes in insulin or oral/noninsulin injectable drug regimens were recorded. RESULTS: Half of the patients (n = 69) were discharged on their preadmission regimen (no change), and a change in the home treatment was recommended in the other half (n = 70). In the group of patients whose preadmission therapy was adjusted, HbA1c decreased from 9.6% (80 mmol/mol) to 8.5% (69 mmol/mol) (P = .0004) 1 year after discharge. In the group of patients discharged on their preadmission regimen, no significant changes in HbA1c levels during the study were observed. At follow-ups occurring 12 to 16 weeks after discharge, 52% (95% CI: 37.4%-66.3%) of patients in the change group had their treatment modified, compared with 18.6% (95% CI: 9.7%-30.9%) in the no-change group. In the group of patients discharged on their preadmission regimen, no significant change was observed. At the beginning of the study, patients in the change treatment group had higher HbA1c levels than patients in the no-change group (9.6 ± 2.0 vs 8.6 ± 1.7, P < .001). At the end of the study, no significant changes in terms of HbA1c levels were found between the groups (8.8 ± 1.9 vs 8.5 ± 1.9, P = .2). CONCLUSIONS: Significant improvement in diabetes control occurred 1 year after hospital discharge in patients who underwent modifications in their treatment. This supports the relevance of providing and implementing proper care recommendations at transition.

Initiation of basal bolus insulin therapy.

Most practice guidelines recommend the use of longacting or pre-mixed insulin at the initiation of insulin therapy in type 2 diabetes, especially in patients not achieving glycaemic goals. Nonetheless, there are some specific indications where basal bolus insulin is the preferred regimen for insulin initiation. These include the "5S" situations - 'Severe' hyperglycaemia, 'Symptomatic' diabetes, 'Sick' diabetes (acute or chronic comorbidity), 'Special' situations (pregnancy, childhood, adolescence) and 'Secondary' diabetes (pancreatic, drug-induced, endocrine disorders). This review describes a practical approach to initiation and follow up of basal bolus insulin regimens.

GlucoTab-guided insulin therapy using insulin glargine U300 enables glycaemic control with low risk of hypoglycaemia in hospitalized patients with type 2 diabetes.

AIMS: To investigate efficacy, safety and usability of the GlucoTab system for glycaemic management using insulin glargine U300 in non-critically ill hospitalized patients with type 2 diabetes (T2D). MATERIALS AND METHODS: In this open, non-controlled single-arm pilot study, glycaemic control at the general ward of a tertiary care hospital was guided by a mobile decision support system (GlucoTab) for basal-bolus insulin dosing using the novel basal insulin analogue insulin glargine U300 for the first time. Glycaemic control was surveilled with capillary glucose measurements and continuous glucose monitoring (CGM). The primary endpoint was efficacy of glycaemic management, defined as the percentage of blood glucose measurements within the target range of 3.9 to 7.8 mmol/L. RESULTS: A total of 30 patients with T2D (12 female; age, 67 ± 11 years; HbA1c, 70 ± 26 mmol/mol; BMI, 31.8 ± 5.6 kg/m2 ; length of study, 8.5 ± 4.5 days) were included. In total, 894 capillary glucose values and 49 846 data points of CGM were available, of which 56.1% of all measured capillary glucose values and 54.3% of CGM values were within the target area (3.9-7.8 mmol/L). Overall capillary mean glucose was 8.5 ± 1.2 and 8.4 ± 1.2 mmol/L assessed by CGM. Time within glucose target improved continuously during the course of treatment, while time within hypoglycaemia (<3.9 mmol/L) decreased substantially. The GlucoTab-suggested total daily dose was accepted by staff in 97.3% of situations. CONCLUSIONS: Treatment with GlucoTab using insulin glargine U300 in hospitalized patients with T2D is effective and safe.

Glycemic control with a basal-bolus insulin protocol in hospitalized diabetic patients treated with glucocorticoids: a retrospective cohort study.

BACKGROUND: Improved glycemic control is the desired outcome after the discharge of patients with diabetes. We aimed to determine the efficacy of a basal-bolus insulin protocol in hospitalized patients with diabetes treated with glucocorticoids. METHODS: A retrospective cohort study compared the glycemic control of 150 hospitalized patients with diabetes and elevated inflammatory markers who were either treated with (n = 61) or without glucocorticoids (n = 89). All patients were treated with a basal-bolus regimen. RESULTS: Glycosylated hemoglobin A1C (HbA1C) levels, mode of diabetes treatment before admission, length of hospitalization and inflammatory markers were similar in both groups of patients (treated and untreated with glucocorticoid). There was a trend toward female predominance in the glucocorticoid-treated group. Mean daily glucose levels were higher in patients taking glucocorticoids when compared with untreated patients (12.5 ± 2.7 mmol/l vs. 10.9 ± 2.4 mmol/l, p < .0001), and significantly higher at 5:00 PM (13.1 ± 3.4 vs. 10.2 ± 3 mmol/l, p < .0001), and 8:00 P.M. (13.9 ± 4.1 mmol/l vs. 11 ± 3.1 mmol/l, p < 0.001) . No difference was detected between the two groups in prandial and basal insulin doses during hospitalization. Overall, 64% of patients in the glucocorticoid-treated group versus 39% in the untreated group had inadequate glycemic control during hospitalization (p = 0.003). CONCLUSION: A significantly higher percentage of patients with diabetes who were treated with glucocorticoids during hospitalization did not achieve glycemic control with a basal-bolus insulin protocol. These patients had significantly higher mean blood glucose levels due to elevated levels in the afternoon and evening. New basal-bolus protocols with appropriate adjustments of short acting insulin are needed to treat patients with diabetes on glucocorticoid therapy.

[Effectiveness of one-year insulin glargine and insulin glulisine basal-bolus treatment in people with type 2 diabetes. An analysis from drug reimbursement perspective]. / A glargin és glulizin inzulinnal folytatott bázis-bolus kezelési rendszer egyéves eredményessége 2-es típusú cukorbetegségben. Elemzés a gyógyszerár-támogatás tükrében.

INTRODUCTION: Being entitled for no patient co-payment, the Hungarian reimbursement condition of analogue insulins as part of basal-bolus treatment in type 2 diabetes mellitus (T2DM) requires that two HbA1c levels should achieve <8.0% target value within 12 months (measured two months apart) after switching from treatment with human insulins. Achieving this target, the treatment should be considered effective from drug reimbursement perspective. AIM: The aims of the study were to investigate the effectiveness of insulin glargine + insulin glulisine basal-bolus regimen from the payer's perspective and to investigate the ability to maintain the achieved glycaemic control in previously uncontrolled T2DM patients (HbA1c >9.0%). METHOD: This one-year, non-interventional study included patients with T2DM inadequately controlled (HbA1c >9.0%) on previous human basal-bolus treatment. The main outcomes were the proportion of patients who achieved the adequate glycaemic control (defined by the reimbursement rules) and the proportion of patients who achieved reimbursement rules defined HbA1c <8.0% target value by the 6 months after switch and could maintain this glycaemic control for upcoming further 6 months. As safety outcome, the hypoglycaemic events were recorded. RESULTS: Out of the 557 patients enrolled, 287 had available data to be included in the efficacy analysis. Out of the 287 efficacy analysis patients, 169 (58.9%) achieved the reimbursement rules defined glycaemic control. At 6 months, 167 patients had HbA1c value <8.0% and 152 (91.0%) remained in this target range until the end of the 12-month observational period. Overall, 1221 non-severe and 6 severe hypoglycaemic events were reported. CONCLUSIONS: More than half of the patients with T2DM who were newly switched to insulin glargine + glulisine basal-bolus treatment could achieve the reimbursement rule criteria requiring for prescription of the analogue insulins with no co-payment beyond 1 year of treatment in Hungary. However, the results revealed that glycaemic control assessment with HbA1c measurements had not met the reimbursement requirements in a significant part of patients. Orv Hetil. 2018; 159(50): 2122-2128.

Efficacy of basal-bolus insulin regimens in the inpatient management of non-critically ill patients with type 2 diabetes: A systematic review and meta-analysis.

Hyperglycemia during hospitalization is associated with increased rates of complications and longer hospital stays. Various insulin regimens are used in the inpatient diabetes management of non-critically ill patients. In this systematic review and meta-analysis, we aimed to assess the efficacy and safety of basal-bolus insulin therapy (BBI) by summarizing evidence from studies of BBI versus sliding scale insulin therapy (SSI) in the management of hospitalized non-critically ill type 2 diabetes patients. We searched MEDLINE, EMBASE, Scopus, and the Cochrane Library for studies comparing BBI therapy with SSI therapy in hospitalized non-critically ill patients with type 2 diabetes. Primary outcome was mean daily blood glucose (BG) during admission. Secondary outcomes were incidence of hypoglycemia and length of hospital stay. Results of included randomized controlled trials (RCT) were pooled and meta-analysed to provide estimates of the efficacy of BBI therapy. Five RCTs and seven observational studies were included in the review. Meta-analysis of RCTs showed significantly lower mean daily BG with BBI than SSI. Mean difference in daily BG between the two regimens ranged from 14 to 29 mg/dl. BBI therapy was associated with increased risk of mild hypoglycemia (BG ≤ 70 mg/dl, RR 5.75; 95% CI 2.79-11.83), (BG ≤ 60 mg/dl, RR 4.21; 95% CI 1.61-11.02) compared with SSI therapy. There was no difference in risk of severe hypoglycemia (BG ≤ 40 mg/dl) and no difference in mean length of stay. In conclusion, basal-bolus insulin in the inpatient diabetes management results in significantly lower mean daily BG than sliding scale insulin but is associated with increased risk of mild hypoglycemia.

Comparison of insulin degludec with insulin detemir in type 1 diabetes: a 1-year treat-to-target trial.

The long-term safety and tolerability of insulin degludec (IDeg) was compared with that of insulin detemir (IDet), as basal treatment in participants with type 1 diabetes mellitus (T1DM). In the present multinational, 26-week core + 26-week extension, controlled, open-label, parallel-group trial, adults with T1DM were randomized to IDeg or IDet as basal insulin treatment combined with meal-time bolus insulin aspart. IDeg was administered once daily, whilst IDet was administered once or twice daily depending on patients' glycaemic control. After 1 year, IDeg provided a 33% lower rate of nocturnal hypoglycaemia compared with IDet: estimated rate ratio (IDeg : IDet) 0.67 [95% confidence interval (CI) 0.51; 0.88]; p < 0.05. IDeg improved glycated haemoglobin after 1 year of treatment, similarly to IDet, but IDeg also provided a significantly greater reduction in fasting plasma glucose compared with IDet: estimated difference (IDeg - IDet) -1.11 (95% CI -1.83; -0.40) mmol/l; p < 0.05. The present study confirmed the long-term safety and tolerability profile of IDeg in patients with T1DM. IDeg provided a lower risk of nocturnal confirmed hypoglycaemia than IDet.

Switching from twice-daily glargine or detemir to once-daily degludec improves glucose control in type 1 diabetes. An observational study.

BACKGROUND AND AIMS: Degludec is an ultralong-acting insulin analogue with a flat and reproducible pharmacodynamic profile. As some patients with type 1 diabetes (T1D) fail to achieve 24-h coverage with glargine or detemir despite twice-daily injections, we studied the effect of switching T1D patients from twice-daily glargine or detemir to degludec. METHODS AND RESULTS: In this prospective observational study, T1D patients on twice-daily glargine or detemir were enrolled. At baseline and 12 weeks after switching to degludec, we recorded HbA1c, insulin dose, 30-day blood glucose self monitoring (SMBG) or 14-day continuous glucose monitoring (CGM), treatment satisfaction (DTSQ), fear of hypoglycemia (FHS). We included 29 patients (mean age 34 ± 11 years; diabetes duration 18 ± 10 years). After switching to degludec, HbA1c decreased from 7.9 ± 0.6% (63 ± 6 mmol/mol) to 7.7 ± 0.6% (61 ± 6 mmol/mol; p = 0.028). SMBG showed significant reductions in the percent and number of blood glucose values <70 mg/dl and in the low blood glucose index (LBGI) during nighttime. CGM showed a significant reduction of time spent in hypoglycemia, an increase in daytime spent in target 70-180 mg/dl, and a reduction in glucose variability. Total insulin dose declined by 17% (p < 0.001), with 24% reduction in basal and 10% reduction in prandial insulin. DTSQ and FHS significantly improved. CONCLUSION: Switching from twice-daily glargine or detemir to once daily degludec improved HbA1c, glucose profile, hypoglycemia risk and treatment satisfaction, while insulin doses decreased. ClinicalTrials.govNCT02360254.

Insulin in ramadan.

Many people with diabetes, both type 1 and type 2, require insulin for maintainance of glycaemic control and health. Most of these people can observe the Ramadan fast, provided appropriate dosage adjustments are made, and basic rules of safety followed. This article describes modifications and precautions that are needed while prescribing insulin during Ramadan.

Randomized, 1-year comparison of three ways to initiate and advance insulin for type 2 diabetes: twice-daily premixed insulin versus basal insulin with either basal-plus one prandial insulin or basal-bolus up to three prandial injections.

AIM: Many patients with type 2 diabetes mellitus (T2DM) initiate insulin therapy when other treatments fail; how best to do this is poorly defined. METHODS: People with T2DM [n = 588; glycated haemoglobin A1C (A1C) >7.0%, mean baseline 9.4%] were randomized to twice-daily premixed protamine-aspart/aspart insulin (PM - 2), once-daily insulin glargine plus zero to one prandial insulin glulisine injection (G + 1), or insulin glargine plus zero to three prandial injections (G + 3). Insulin was titrated for 60 weeks. Efficacy and safety outcomes were assessed. RESULTS: Discontinuation rates were 53 of the 194 (27%), 44 of the 194 (23%) and 38 of the 194 (20%), for PM - 2, G + 1 and G + 3. Glycaemic control improved in all groups (A1C 7.2 ± 1.37, 7.1 ± 1.68 and 7.0 ± 1.21% at 60 weeks; 7.5 ± 1.29, 7.2 ± 1.62 and 7.2 ± 1.63% at endpoint). G + 1 was statistically non-inferior to PM - 2 in reducing A1C. G + 3 was slightly superior to PM - 2 in attaining <7.0% at 60 weeks, but only when the analysis included Good Clinical Practice non-adherent sites. Hypoglycaemia with plasma glucose <2.8 mmol/l was more frequent with PM - 2 versus G + 1 and G + 3; [adjusted incidence: 46 (p = 0.0087) vs. 33 (p = 0.0045) and 31.5%; events per patient-year: 1.9 vs. 0.8 and 0.9, p ≤ 0.0001]. Insulin dosage and weight-gain were similar. CONCLUSION: Basal insulin plus a single prandial injection is as effective in improving glycaemic control as premixed insulin. Full basal-prandial therapy is only slightly more effective than premixed insulin. Stepwise basal-prandial regimens improve glycaemic control with less hypoglycaemia than twice-daily premixed insulin.

Effectiveness, Simplification and Persistence of IDegLira in Poorly Controlled People with Type 2 Diabetes: A 4-Year Follow-Up Real-World Study.

INTRODUCTION: Efficacy and safety of the fixed ratio combination of insulin degludec and liraglutide (IDegLira) has been largely documented. However, long-term data are limited. This study aimed at describing persistence in therapy and the effectiveness at 48 months of IDegLira. METHODS: We conducted an observational study based on retrospective chart review. All patients treated with IDegLira during 2018-2022 were included. Data on treatment approaches and clinical outcomes were collected at the first prescription of IDegLira (T0) and after 6, 12, 24, 36, and 48 months. RESULTS: Overall, 156 patients (mean age 68 years, 64.1% men) started IDegLira, of whom 88 (56.4%) were previously treated with basal-oral therapy (BOT) and 68 (43.6%) with basal-bolus schemes (BB). Before starting IDegLira, 23.8% were treated with ≥ 2 oral antihyperglycemic agents in association with insulin; at T0, the proportion decreased to 3.2%. Short-acting insulin was discontinued after the first week. After 48 months, levels of HbA1c were significantly reduced by 1.34% in the BOT group and 1.07% in the BB group (p < 0.0001 in both groups). In the BOT group, FBG levels decreased by about 50 mg/dl and body weight was unchanged. In the BB group, FBG levels decreased by about 40 mg/dl and body weight was significantly reduced by an average of 7.7 kg. Five patients (3.2%) interrupted therapy with IDegLira during 48 months, and no severe hypoglycemia occurred. CONCLUSIONS: Our study emphasizes the important role of IDegLira in maintaining a good metabolic control while minimizing the risk of major hypoglycemia and weight gain in the long term. The substantial simplification of treatment schemes can increase adherence.

Flash Glucose Monitoring is Associated with HbA1c Improvement in Type 2 Diabetes Managed with Multiple Daily Injections of Insulin in the UK: A Retrospective Observational Study.

INTRODUCTION: There is a growing body of evidence demonstrating the benefit of flash glucose monitoring in people living with type 2 diabetes mellitus (T2DM). This real-world study aimed to evaluate the effect of initiating flash glucose monitoring on change in HbA1c after 3-6 months in adults living with T2DM treated with multiple daily injections of insulin. METHODS: A retrospective observational study using data from ten clinical centres in the UK for adults with T2DM treated with multiple daily injections of insulin for at least 1 year was conducted. Patients who had been using the FreeStyle Libre/Libre 2 Flash Glucose Monitoring System for at least 3 months with baseline HbA1c 64-108 mmol/mol (8.0-12.0%) recorded up to 3 months prior to system use were included. Pregnant patients and those on dialysis were excluded. Patients with an HbA1c value measured 3-6 months after commencing flash glucose monitoring were included in the final analysis for evaluation of change. RESULTS: In total, 87 patients were included in the final analysis (mean age, 60.0 ± 11.8 years, 60.9% male, mean body mass index (BMI), 31.6 ± 5.4 [mean ± SD]). From a mean baseline HbA1c of 80 ± 11 mmol/mol (9.5% ± 1.0%), HbA1c lowered by 11 ± 14 mmol/mol (1.0% ± 1.3%) at 3-6 months (p < 0.0001). A decrease was observed independent of age, baseline HbA1c, sex, duration of insulin use and BMI subgroups. CONCLUSIONS: Initiation of flash glucose monitoring was associated with a clinically and statistically significant improvement in HbA1c in a real-world setting at 3-6 months.

A dose titration protocol for once-daily insulin glargine 300 U/mL for the treatment of diabetes mellitus in dogs.

BACKGROUND: In purpose-bred dogs, insulin glargine 300 U/mL (IGla300) has long duration of action, peakless time-action profile, and low potency, making it suitable for use as a basal insulin. HYPOTHESIS: To evaluate IGla300 in client-owned diabetic dogs monitored using a flash glucose monitoring system (FGMS). ANIMALS: Ninety-five client-owned diabetic dogs, newly diagnosed or previously treated with other insulin formulations, with or without concurrent diseases. METHODS: Prospective multi-institutional study. Clinical signs and standardized assessment of FGMS data, using treatment and monitoring guidelines established a priori, guided dose adjustments and categorization into levels of glycemic control. RESULTS: The initial IGla300 dose was 0.5 U/Kg q24h for newly diagnosed dogs and (median dose [range]) 0.8 U/Kg (0.2-2.5) q24h for all dogs. Glycemic control was classified as good or excellent in 87/95 (92%) dogs. The IGla300 was administered q24h (1.9 U/kg [0.2-5.2]) and q12h (1.9 U/kg/day [0.6-5.0]) in 56/95 (59%) and 39/95 (41%) dogs, respectively. Meal-time bolus injections were added in 5 dogs (0.5 U/kg/injection [0.3-1.0]). Clinical hypoglycemia occurred in 6/95 (6%) dogs. Dogs without concurrent diseases were more likely to receive IGla300 q24h than dogs with concurrent diseases (72% vs 50%, respectively; P = .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Insulin glargine 300 U/mL can be considered a suitable therapeutic option for once-daily administration in diabetic dogs. Clinicians should be aware of the low potency and wide dose range of IGla300. In some dogs, twice-daily administration with or without meal-time bolus injections may be necessary to achieve glycemic control. Monitoring with FGMS is essential for dose titration of IGla300.

A prospective, multicentre, randomized, open-label comparison of a long-acting basal insulin analog glargine plus glulisine with premixed insulin in insulin naïve patients with Type 2 diabetes - A study from India.

AIMS: We aimed to compare the effectiveness of Glargine plus Glulisine to premixed insulin analogue, as measured by HbA1c ≤ 7.0% in insulin naive Type 2 Diabetes (T2D) patients with elevated fasting and/or postprandial plasma glucose. METHODS: Insulin-naive T2D patients (116 men, 84 women) on ≥ 2 oral hypoglycemic agents with inadequate glycemic control were randomized either to group 1 (insulin Glargine plus Glulisine, n = 101) or group 2 (Premixed Insulin analogue, n = 99). RESULTS: In the intention to treat analysis, at week 24, percentage of patients with good glycaemic control (HbA1c ≤ 7.0%) was similar between the two groups (16.8% in Group 1 vs. 13.1% in Group 2, χ2 - 0.535, p = 0.47). Significant reductions in fasting and postprandial levels were observed in groups 1 and 2 at both post-baseline time points (Week 12 and 24). In group 1, reduction in HbA1c from baseline to week 12 was 0.6 ± 0.1 and 0.7 ± 0.2 at week 24, p < 0.0001 for all. In group 2, no significant change in HbA1c was observed. In group 1, 83.2% required an additional dose of glulisine and in group 2, 88.9% required an additional dose of premixed insulin. Hypoglycemic events were similar in both groups (0.12 events per person-year in group 1 and 0.13 events per person-year in group 2). Weight gain was non-significant in both groups. CONCLUSIONS: Glargine plus Glulisine, though in higher dose was effective as premixed insulin in lowering HbA1c. Hypoglycemic events per person-year were similar in both groups.

BEYOND 2 years: durability of metabolic benefits by simplification of complex insulin regimens in type 2 diabetes.

PURPOSE: To assess the magnitude and durability of the metabolic benefits by simplification of complex insulin treatments in patients with type 2 diabetes inadequately controlled by a full basal-bolus insulin regimen. Herein we report the results of the scheduled 2-year extension of the BEYOND trial. METHODS: Originally, 305 participants with inadequate glycemic control (HbA1c > 7.5%) were randomly assigned to intensification of basal-bolus insulin regimen (n = 101), to a fixed-ratio combination (basal insulin + GLP-1RA, n = 102), or to an association of basal insulin plus an SGLT-2 inhibitor (gliflo-combo, n = 102). The primary efficacy outcome was change from baseline in HbA1c at 24 months assessed by an intention-to-treat analysis. A per-protocol analysis was also performed. RESULTS: Fifty-five percent of patients completed the study in the two comparison arms. Compared with patients randomized to basal-bolus, patients of the other groups experienced non statistically different reductions in HbA1c level according to either an intention-to-treat analysis (-0.8 ± 1.1%, -0.7 ± 1.1%, and -1.3 ± 1.1%, mean ± SD, fixed-ratio, gliflo-combo and basal bolus, respectively) or per-protocol analysis (-1.2 ± 1.0%, -1.2 ± 1.1%, and -1.3 ± 1.0%, respectively). The final HbA1c level (per protocol) was 7.2 ± 0.8%, 7.3 ± 0.9%, and 7.5 ± 0.9%, respectively (P = NS). Treatment satisfaction (DTSQ) increased in both exchange groups, whereas the proportion of patients with hypoglycemia was lower. CONCLUSION: Simplification of complex insulin regimen may be a durable option in at least one-half of patients with type 2 diabetes. CLINICAL TRIAL REGISTRATION: Clinical trial registration no. NCT04196231, clinicaltrials.gov.

Efficacy and safety of basal-bolus insulin at 1:1.5 ratio compared to 1:1 ratio using a weight-based initiation and titration (WIT2) algorithm in hospitalized patients with type 2 Diabetes: a multicenter, randomized, clinical study.

BACKGROUND: Most studies initiated basal-bolus insulin in a ratio of 1:1 and titrated based on glucose. This study aimed to investigate the effectiveness and safety of a weight-based and ratio of 1:1.5 basal-bolus insulin using an algorithm for both initiation and titration in hospitalized patients with type 2 diabetes (T2D). METHODS: Hospitalized patients with T2D were randomly assigned to two groups in equal numbers to receive 1:1.5 and 1:1 ratios of basal-bolus insulin using a weight-based algorithm for both initiation and titration. The primary outcome was the time taken to reach the fasting blood glucose (FBG) target and 2-h postprandial blood glucose (2hBG) targets after three meals. The secondary outcome included insulin dosage to achieve glycemic control and the incidence of hypoglycemia during hospitalization. RESULTS: 250 patients were screened between October 2021 and June 2022, 220 were randomly grouped, and 182 completed the trial (89 in the 1:1.5 and 93 in the 1:1 groups). The time taken to reach FBG targets was comparable between the two groups (3.4 ± 1.7 vs. 3.0 ± 1.3 days, p = 0.137) within about 3 days. The 2hBG after three meals was shorter in the 1:1.5 group than in the 1:1group (2.9 ± 1.5 vs. 3.4 ± 1.4 days, p = 0.015 for breakfast, 3.0 ± 1.6 vs. 3.6 ± 1.4 days, p = 0.005 for lunch, and 3.1 ± 2.1 vs. 4.0 ± 1.5 days, p = 0.002 for dinner). No significant difference in insulin dosages was found between the two groups at the end of the study. The incidence of hypoglycemia was similar in both groups. CONCLUSIONS: We demonstrated that fixed dose-ratio basal-bolus insulin at 1:1.5 calculated using a weight-based initiation and titration algorithm was simple, as effective, and safe as ratio at 1:1 in managing T2D in hospitalized patients. Trial Registration ChiCTR 2,100,050,963. Date of registration: September 8, 2021.

Insulin Therapy in Small Animals, Part 3: Dogs.

Insulin therapy should ideally mimic a basal-bolus pattern. Lente, NPH, NPH/regular mixes, PZI, glargine U100, and detemir are intermediate-acting formulations that are administered twice daily in dogs. To minimize hypoglycemia, intermediate-acting insulin protocols are usually geared towards alleviating (but not eliminating) clinical signs. Insulin glargine U300 and insulin degludec meet the criteria for an effective and safe basal insulin in dogs. In most dogs, good control of clinical signs is achieved when using a basal insulin alone. In a small minority, bolus insulin at the time of at least one meal per day may be added to optimize glycemic control.