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.

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.

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.

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.

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.

Unmasking Type 1 Diabetes in Adults: Insights From Two Cases Revealing Misdiagnosis As Type 2 Diabetes, With Emphasis on Autoimmunity and Continuous Glucose Monitoring.

Type 1 diabetes mellitus (T1DM) is often misdiagnosed as type 2 diabetes mellitus (T2DM) in adults, resulting in inadequate treatment and poor disease management. In this report, we present two patients initially misdiagnosed with T2DM for 14 and four years, respectively, leading to complications like diabetic ketoacidosis (DKA). Reevaluation confirmed adult-onset T1DM through antibody tests. Treatment was adjusted to a basal-bolus insulin regimen with the use of continuous glucose monitoring (CGM). The correct diagnosis and CGM implementation significantly improved diabetes mellitus management. This case report emphasizes the importance of mindful diagnosis in adult patients with diabetes mellitus, considering both type 1 and type 2 differentials.

Switching from Multiple Insulin Injections to a Fixed Combination of Degludec and Liraglutide in Patients with Type 2 Diabetes Mellitus: Results from the Simplify Study After 6 Months.

INTRODUCTION: This study aimed to evaluate the effectiveness and safety of switching from basal bolus insulin treatment (BBIT) to a fixed combination of insulin degludec and liraglutide (IDegLira) in patients with type 2 diabetes mellitus (T2DM) who had preserved insulin secretion but inadequate glucose control. The study also aimed to assess the feasibility of implementing this therapeutic approach in common clinical practice settings. METHODS: This was a non-randomized, open-label, multicenter, prospective, single-arm study involving 234 patients with T2DM who were receiving BBIT. Inclusion criteria were duration of diabetes mellitus > 60 months, stable total daily dose of insulin (TDDI) ranging from > 20 to < 70 IU/day (approx. > 0.3 to < 0.7 IU/kg body weight/day), C-peptide levels > 10% above the lower limit, HbA1c levels > 7% and < 10% (Diabetes Control and Complications Trial), and body mass index > 25 kg/m2. The primary endpoints were changes in glycated hemoglobin (HbA1c) and body weight at week 28 after treatment switching. Secondary endpoints included changes in the 7-point glycemic profile, hypoglycemia frequency, blood pressure, blood lipids, liver enzymes, insulin dose, and a patient questionnaire focusing on treatment satisfaction, concerns and impact on daily activities. A subgroup of 55 patients underwent continuous glucose monitoring (CGM) with the evaluation of CGM-derived parameters, such as time in range (TIR), time above range (TAR), time below range (TBR), hypoglycemia, and glucose variability. RESULTS: A significant decrease in HbA1c (8.6% vs. 7.6%; p < 0.0001) and body weight (97.8 vs. 94.0 kg; p < 0.0001) was observed at week 28 after treatment switching. Significant improvements were also seen in all measurements of the 7-point glycemic profile (p < 0.0001), reduction in the number of hypoglycemia episodes per patient, and the proportion of patients with at least one hypoglycemia event (p < 0.001). Furthermore, there was a significant decrease in daily insulin dose (55.6 vs. 32.7 IU/day; p < 0.0001), as well as improvements in blood pressure, blood lipids, and liver enzymes (gamma glutamyl transferase and alanine aminotransferase). The subgroup of patients who underwent CGM showed a significant increase in TIR (57.9% vs. 69.0%; p < 0.01) and a decrease in TAR (40.1% vs. 28.8%; p < 0.01), while TBR, hypoglycemia (number of episodes per patient and proportion of patients), and glucose variability did not change significantly. CONCLUSION: The results of this study suggest that switching from BBIT to IDegLira in patients with T2DM and preserved insulin secretion can simplify treatment without compromising glycemic control. The switch to IDegLira was associated with significant improvements in various glucose control parameters, including HbA1c, glycemic profile, hypoglycemia, insulin doses, and CGM-derived parameters TIR and TAR. Additionally, it led to significant reductions in body weight, blood pressure, lipid profile, and liver enzyme levels. Switching to IDegLira may be considered a safe and beneficial approach in clinical practice settings, offering metabolic and individual advantages.

Diabetes-related outcomes with basal-bolus vs. premixed insulin among veterans with type 2 diabetes: A single institutional retrospective study.

BACKGROUND: The purpose of this study was to compare diabetes (DM)-related outcomes between basal-bolus (BB) and premixed (PM) insulin regimens. METHODS: Retrospective chart review including veterans with type 2 diabetes (T2DM), ≥18 years old with hemoglobin A1c (HbA1c) ≥8%. Outcomes were assessed after one year of BB or PM insulin therapy. Data were analyzed using Chi-square/Fisher exact tests and logistic regression. RESULTS: Out of 140 enrolled subjects (70 BB and 70 PM), 94% were males with average age and duration of DM of 65.7 ± 10.1 and 12.9 ± 9 years, respectively. The BB and PM groups were similar in age, gender distribution, HbA1c, body mass index (BMI) and DM duration at baseline. Following 1 year of treatment, there was no significant difference between the groups for change in HbA1c (-1.9 ± 1.8 vs -2.1 ± 1.9%, p = 0.3) or hypoglycemia rate (30% vs 21.4%, p = 0.3), respectively. There was similar increase in average BMI in both groups (0.84 ± 3.1 for BB vs 0.4 ± 2.2 kg/m2 for PM, p = 0.2). CONCLUSIONS: There were no significant differences for glycemic control, hypoglycemia rate or BMI between the BB or PM insulin groups. These results suggest PM insulin is equally effective and safe as BB insulin.

Cushing's Syndrome and Other Causes of Insulin Resistance in Dogs.

The most common causes of insulin resistance in diabetic dogs are Cushing syndrome, diestrus, and obesity. Cushing-associated effects include insulin resistance, excessive postprandial hyperglycemia, perceived short duration of insulin action, and/or substantial within-day and/or day-to-day glycemic variability. Successful strategies to manage excessive glycemic variability include basal insulin monotherapy and combined basal-bolus insulin treatment. Ovariohysterectomy and insulin treatment can achieve diabetic remission in about 10% of cases of diestrus diabetes. Different causes of insulin resistance have an additive effect on insulin requirements and the risk of progression to clinical diabetes in dogs.

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.

Long-term field study of lispro and neutral protamine Hagedorn insulins treatment in dogs with diabetes mellitus.

BACKGROUND: The long-term clinical and biofhemical effects of basal-bolus insulin treatment with lispro and NPH in dogs with diabetes mellitus are undocumented. OBJECTIVES: To perform a prospective pilot field study of the long-term effects of lispro and NPH on clinical signs and serum fructosamine concentrations (SFC) in dogs with diabetes mellitus. METHODS: Twelve dogs received combined lispro and NPH insulins treatment twice a day and were examined every 2 weeks for 2 months (visits 1-4), and every 4 weeks for up to 4 additional months (visits 5-8). Clinical signs and SFC were recorded at each visit. Polyuria and polydipsia (PU/PD) were scored as absent (0) or present (1). RESULTS: Median (range) PU/PD scores of combined visits 5-8 (0, 0-1) were significantly lower than median scores of combined visits 1-4 (1, 0-1, p = 0.03) and at enrolment (1, 0-1, p = 0.045). Median (range) SFC of combined visits 5-8 (512 mmol/L, 401-974 mmol/L) was significantly lower than SFC of combined visits 1-4 (578 mmol/L, 302-996 mmol/L, p = 0.002) and at enrolment (662 mmol/L, 450-990 mmol/L, p = 0.03). Lispro insulin dose was significantly and negatively, albeit weakly, correlated with SFC concentration during visits 1 through 8 (r = -0.3, p = 0.013). Median duration of follow up was 6 months (range 0.5-6) and most dogs (8, 66.7%) were followed for 6 months. Four dogs withdrew from the study within 0.5-5 months because of documented or suspected hypoglycaemia, short NPH duration or sudden unexplained death. Hypoglycaemia was noted in 6 dogs. CONCLUSIONS: Long-term lispro and NPH combination therapy may improve clinical and biochemical control of some diabetic dogs with comorbidities. Risk of hypoglycaemia should be addressed with close monitoring.

An Indirect Comparison of Basal Insulin Plus Once-Weekly Semaglutide and Fully Optimised Basal-Bolus Insulin in Type 2 Diabetes.

INTRODUCTION: To date, there have been few head-to-head comparisons between semaglutide once-weekly (OW) and short-acting meal-time insulin in participants with type 2 diabetes (T2D) treated with basal insulin and requiring treatment intensification. This indirect comparison evaluated the effects of these regimens on glycated haemoglobin (HbA1c), body weight, hypoglycaemia, and other clinically relevant outcomes. METHODS: A post-hoc, unanchored, individual participant data meta-analysis was conducted on the basis of data from single treatment arms in the SUSTAIN 5 and DUAL 7 trials. Semaglutide 0.5 mg OW and 1.0 mg OW plus basal insulin were compared with an optimised (treat-to-target) basal-bolus regimen of insulin glargine and insulin aspart over 26 weeks, using regression adjustment to account for baseline differences between the trials. RESULTS: Over 26 weeks, semaglutide 1.0 mg OW plus basal insulin reduced mean HbA1c by significantly more than the basal-bolus regimen (treatment difference: - 0.36%; p = 0.003), while semaglutide 0.5 mg OW plus basal insulin was comparable with basal-bolus insulin (treatment difference: 0.08%, p = 0.53). Both doses of semaglutide were associated with significant weight loss relative to insulin intensification (treatment differences: 6.8-9.4 kg; p < 0.001). At both doses, semaglutide intensification required less basal insulin per day than bolus intensification, and more participants on semaglutide met HbA1c targets of < 7.0% and ≤ 6.5% without hypoglycaemia or weight gain (odds ratio [OR] for < 7.0%, 21.9; OR for ≤ 6.5%, 16.2; both p < 0.001). CONCLUSIONS: In T2D uncontrolled by basal insulin, intensification with semaglutide 1.0 mg OW was associated with better glycaemic control, weight loss, and reduced hypoglycaemia versus a basal-bolus regimen, while limiting the treatment burden associated with frequent injections. Clinicians could consider treatment intensification with semaglutide when T2D is uncontrolled by basal insulin, especially when weight management is a priority. Effective glycaemic control coupled with weight management can alleviate the burden of diabetes-associated complications.

Nanotechnology: Newer Approach in Insulin Therapy.

Insulin is a peptide hormone released by pancreatic beta cells. An autoimmune reaction in diabetes mellitus type 1 causes the beta cells to die, preventing insulin from being produced or released into the bloodstream; that impacts 30 million people globally and is linked to shortened lifespan due to acute and chronic repercussions. Insulin therapy aims to replicate normal pancreatic insulin secretion, which includes low levels of insulin that are always present to support basic metabolism, as well as the two-phase secretion of additional insulin in response to high blood sugar - an initial spike in secreted insulin, followed by an extended period of continued insulin secretion. This is performed by combining various insulin formulations at varying rates and lengths of time. Since the beginning of human insulin use, several advances in insulin formulations have been made to help meet these aims as much as possible, resulting in improved glycaemic control while limiting hypoglycemia. In this review, we looked at devices used by patients with type 1 diabetes, such as insulin pumps, continuous glucose monitors, and, more recently, systems that combine a pump with a monitor for algorithm-driven insulin administration automation. We intend to provide insight into supplementary therapies and nanotechnology employed in insulin therapy as a result of our review.

De-intensification of basal-bolus insulin regimen after initiation of a GLP-1 RA improves glycaemic control and promotes weight loss in subjects with type 2 diabetes.

AIMS: To evaluate the impact of adding a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in people with type 2 diabetes (T2D) in basal-bolus (BB) insulin regimen, on insulin requirement, HbA1c, weight loss up to 24 months. METHODS: Data on subjects with T2D on BB who initiated a GLP-1 RA have been retrospectively collected. HbA1c, body weight, and insulin dose were recorded at baseline, 6, 12, and 24 months after initiation of GLP-1 RA therapy. A linear mixed model for repeated measures was used to evaluate the changes in HbA1c, body weight, and insulin requirement over time. RESULTS: We included 156 subjects (63.5% males; age 62 ± 11 years, HbA1c 70 ± 22.0 mmol/mol; 8.6 ± 4.2%). Compared to baseline, HbA1c and body weight were significantly lower at 6 months after introducing a GLP-1RA and remained stable up to 24 months (all p < 0.0001 vs. baseline). At 24 months, 81% of subjects discontinued prandial insulin, while 38.6% discontinued basal insulin as well. Insulin requirement at baseline (aOR 0.144; 95% CI, 0.046-0.456; P = 0.001) was the only significant predictor of prandial insulin discontinuation. CONCLUSIONS: Replacing prandial insulin with GLP-1 RA is a valuable strategy to simplify the BB insulin regimen while improving glycaemic control and promoting weight loss in subjects with T2D.

IDegLira for the Real-World Treatment of Type 2 Diabetes in Italy: Protocol and Interim Results from the REX Observational Study.

INTRODUCTION: IDegLira was shown to maintain glycemic control while reducing risk of hypoglycemia and body weight gain. The REX study was designed to generate real-world evidence on the use of IDegLira in Italian clinical practice in two different subgroups of patients, those switching to IDegLira from a basal insulin-supported oral therapy (BOT group) and those from a basal plus bolus insulin regimen (BB group). METHODS: Adult patients with T2D diagnosed for at least 12 months and having started IDegLira 2-3 months prior to enrolment, coming from a BOT or BB regimen, were enrolled in this multicenter observational prospective cohort study conducted in 28 Italian centers. This paper presents the methodological framework of the REX study and provides the interim analysis results describing the patients' baseline characteristics and the clinical reasons for IDegLira treatment initiation. RESULTS: Of the 360 patients enrolled in the REX study, 331 were considered eligible for this interim analysis, 76.4% in the BOT and 23.6% in the BB group. Mean (SD) HbA1c was 8.5% (1.4) in the BOT and 8.2% (1.7) in the BB group. The most common T2D complications were diabetic macroangiopathy and diabetic nephropathy in both groups. The median (interquartile range) insulin daily dose before IDegLira was 15.0 (10.0-20.0) units in the BOT group and 42 (30.0-52.0) in the BB group. Oral antidiabetics were taken by 98% and 51.3% of patients, respectively. The main reason for switching to IDegLira was the inadequate glycemic control in the BOT group (86% of patients), and the intent to simplify the treatment in the BB group (66.7%). CONCLUSIONS: IdegLira is initiated after BOT in inadequately controlled patients to improve glycemic control, whereas in BB patients it is used to simplify the therapeutic regimen. Final results of the REX study will shed light on patients' outcomes after IdegLira treatment under routine clinical care.

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.

Outcomes of "Real-World" Insulin Strategies in the Management of Hospital Hyperglycemia.

CONTEXT: Guidelines recommend scheduled long-acting basal and short-acting bolus insulin several times daily to manage inpatient hyperglycemia. In the "real world," insulin therapy is complicated, with limited data on the comparative effectiveness of different insulin strategies. OBJECTIVE: This work aimed to evaluate the association of different insulin strategies with glucose control and hospital outcomes after adjustment for patient and physician factors that influence choice of therapy. METHODS: This retrospective, observational study took place at an academic hospital. Participants included noncritically ill hospitalized medical/surgical patients (n = 4558) receiving subcutaneous insulin for 75% or longer during admission. Insulin therapy was grouped into 3 strategies within the first 48 hours: basal bolus (BB: scheduled long and short/rapid n = 2358), sliding scale (SS: short/rapid acting n = 1855), or basal only (BO: long only: n = 345). Main outcome measures included glucose control: hypoglycemic days, hyperglycemic days, euglycemic days, mean glucose; and hospitalization: in-hospital mortality, length of stay (LOS), and readmissions. RESULTS: Initial therapy with BB was associated with more hypoglycemic (2.40; CI, 2.04 to 2.82) (P < .001) and fewer euglycemic days (0.90; CI, 0.85 to 0.97) (P = .003) than SS, whereas BO was associated with fewer hyperglycemic days (0.70; CI, 0.62 to 0.79) (P < .001), lower mean glucose (-18.03; CI, -22.46 to -12.61) (P < .001), and more euglycemic days (1.22; CI, 1.09 to 1.37) (P < .001) compared to SS. No difference in mortality, LOS, and readmissions was found. However, decreased LOS was observed in the BB subgroup with a medical diagnostic related group (0.93; CI, 0.89 to 0.97) (P < .001). CONCLUSION: BO had a more favorable hyperglycemia profile than SS. BB, on the other hand, showed worse glycemic control as compared to SS. In the real-world hospital, BO may be a simpler and more effective insulin strategy.