Glargine Research Articles

Cardiovascular Outcomes in GRADE (Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness Study).

Cardiovascular disease is a major cause of morbidity and mortality in patients with type 2 diabetes. The effects of glucose-lowering medications on cardiovascular outcomes in individuals with type 2 diabetes and low cardiovascular risk are unclear. We investigated cardiovascular outcomes by treatment group in participants randomly assigned to insulin glargine, glimepiride, liraglutide, or sitagliptin, added to baseline metformin, in GRADE (Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness Study). A total of 5047 participants with a mean±SD age of 57.2±10.0 years, type 2 diabetes duration of 4.0±2.7 years, and low baseline prevalence of cardiovascular disease (myocardial infarction, 5.1%; cerebrovascular accident, 2.0%) were followed for a median of 5 years. Prespecified outcomes included between-group time-to-first event analyses of MACE-3 (composite of major adverse cardiovascular events: cardiovascular death, myocardial infarction, and stroke), MACE-4 (MACE-3+unstable angina requiring hospitalization or revascularization), MACE-5 (MACE-4+coronary revascularization), MACE-6 (MACE-5+hospitalization for heart failure), and the individual components. MACE outcomes and hospitalization for heart failure in the liraglutide-treated group were compared with the other groups combined using Cox proportional hazards models. MACE-6 was also analyzed as recurrent events using a proportional rate model to compare all treatment groups. We observed no statistically significant differences in the cumulative incidence of first MACE-3, MACE-4, MACE-5, or MACE-6, or their individual components, by randomized treatment group. However, when compared with the other treatment groups combined, the liraglutide-treated group had a significantly lower risk of MACE-5 (adjusted hazard ratio, 0.70 [95% CI, 0.54-0.91]; P=0.021), MACE-6 (adjusted hazard ratio, 0.70 [95% CI, 0.55-0.90]; P=0.021), and hospitalization for heart failure (adjusted hazard ratio, 0.49 [95% CI, 0.28-0.86]; P=0.022). Compared with the liraglutide group, significantly higher rates of recurrent MACE-6 events occurred in the groups treated with glimepiride (rate ratio, 1.61 [95% CI, 1.13-2.29]) or sitagliptin (rate ratio 1.75; [95% CI, 1.24-2.48]). This comparative effectiveness study of a contemporary cohort of adults with type 2 diabetes, largely without established cardiovascular disease, suggests that liraglutide treatment may reduce the risk of cardiovascular events in patients at relatively low risk compared with other commonly used glucose-lowering medications. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01794143.

Reduction of prevalence of patients meeting the criteria for metabolic syndrome with tirzepatide: a post hoc analysis from the SURPASS Clinical Trial Program

BackgroundMetabolic syndrome is characterized as the co-occurrence of interrelated cardiovascular risk factors, including insulin resistance, hyperinsulinemia, abdominal obesity, dyslipidemia and hypertension. Once weekly tirzepatide is approved in the US and EU for the treatment of type 2 diabetes (T2D) and obesity. In the SURPASS clinical trial program for T2D, tirzepatide demonstrated greater improvements in glycemic control, body weight reduction and other cardiometabolic risk factors versus placebo, subcutaneous semaglutide 1 mg, insulin degludec, and insulin glargine. This post hoc analysis assessed the effect of tirzepatide use on the prevalence of patients meeting the criteria for metabolic syndrome across SURPASS 1–5.MethodsMetabolic syndrome was defined as having ≥ 3 of 5 criteria according to the US National Cholesterol Education Program: Adult Treatment Panel III. Analyses were based on on-treatment data at the primary endpoint from patients adherent to treatment (taking ≥ 75% study drug). A logistic regression model with metabolic syndrome status as the response variable, metabolic syndrome status at the baseline visit as an adjustment, and randomized treatment as fixed explanatory effect was used. The effect of tirzepatide use on the prevalence of patients meeting the criteria for metabolic syndrome by categorical weight loss, background medication and gender were assessed.ResultsIn SURPASS, the prevalence of patients meeting the criteria for metabolic syndrome at baseline was 67–88% across treatment groups with reductions at the primary endpoint to 38–64% with tirzepatide versus 64–82% with comparators. Reductions in the prevalence of patients meeting the criteria for metabolic syndrome was significantly greater with all tirzepatide doses versus placebo, semaglutide 1 mg, insulin glargine, and insulin degludec (p < 0.001). Individual components of metabolic syndrome were also reduced to a greater extent with tirzepatide vs comparators. Greater reductions in body weight were associated with greater reductions in the prevalence of patients meeting the criteria for metabolic syndrome and its individual components. Background SGLT2i or sulfonylurea use or gender did not impact the change in prevalence of patients meeting the criteria for metabolic syndrome.ConclusionsIn this post hoc analysis, tirzepatide at all doses studied was associated with a greater reduction in the prevalence of patients meeting the criteria for metabolic syndrome compared to placebo, semaglutide 1 mg, insulin degludec, and insulin glargine. Although more evidence is needed, these data would support greater potential improvement in cardiovascular risk factor profile with tirzepatide treatment in people across the continuum of T2D.

Oxidative stress and inflammatory markers in streptozotocin-induced acute and subacute toxicity response

Streptozotocin (STZ) is used as a diabetes-inducing agent in experimental animal studies. However, it is known that STZ-induced diabetic animals show significant increases in oxidative stress parameters and neurodegeneration besides their blood glucose level. In this study, the acute and subacute toxic effects of STZ on the liver, sciatic nerve, and brain tissues were investigated in vivo rat model. Sprague-Dawley rats were divided into two groups; while 50 mg/kg STZ was administered ip to the STZ group, only saline was administered to the control group. After STZ administration, three units (100 U/mL) of subcutaneous insulin glargine were applied daily to prevent the formation of diabetes. At 24 h, 1,2, and 4 weeks after applications, rats from each group were sacrificed and tissues were removed under anesthesia. At the end of the study, compared to the control, a significant decrease in SOD and GST activity and an increase in lipid peroxidation were detected in the liver and sciatic tissues of rats in the STZ-treated group in the first 24h. Considering the TUNEL, NFκB, and NOS2 expressions, it was noted that while the effects of STZ on the liver were observed in the acute stage (24h), it had subacute effects on the brain. When apoptosis-related gene expression (Bcl-2, Bax, CASP3, CASP8, CASP9, TNF-α) and immunohistochemistry were evaluated, the apoptotic effect of STZ was observed mostly in sciatic nerve tissues. Within the scope of the study, it was revealed that STZ did not only show selective toxicity to pancreatic β cells but also very toxic to other tissues and organs.

Effectiveness and safety of insulin glargine U-300 as compared to insulin glargine U-100 in oral antidiabetic (OAD) failure cases—record-based observational study

Effectiveness and safety of insulin glargine U-300 as compared to insulin glargine U-100 in oral antidiabetic (OAD) failure cases—record-based observational study

Retrospective Analysis of Once-Daily Versus Twice-Daily Insulin Glargine Dosing in Noncritically Ill Individuals.

Insulin is the treatment of choice for diabetes care in the hospital. There is some debate regarding the efficacy and safety of once-daily versus twice-daily insulin glargine in the hospital, particularly in the critically ill population. The purpose of this pilot study was to evaluate the efficacy and safety of insulin glargine administered as a once-daily versus twice-daily regimen in the noncritically ill population. A retrospective chart review was conducted from 1 June 2020 to 31 May 2021. Inclusion criteria were age ≥18 years and on a regimen of either once-daily or twice-daily insulin glargine for ≥72 hours during the specified time frame. The primary end point was a comparison of the number of days with all blood glucose measurements within the range of 70-180 mg/dL throughout a 24-hour period. Secondary end points included the number of hyperglycemic (>180 mg/dL) and hypoglycemic (<70 mg/dL) events that occurred in each study group. Group 1 included 101 individuals who received once-daily dosing, and group 2 included 103 individuals who received twice-daily dosing. Baseline characteristics were similar between the groups except for a higher BMI at admission (P = 0.01) and a higher pre-admission A1C (P = 0.02) in group 2. No differences were found for the primary end point (P = 0.5) or for hypoglycemic (P = 0.6) or hyperglycemic (P = 0.7) events. There were no significant differences in efficacy or safety between once-daily and twice-daily insulin glargine in the noncritically ill population. A larger prospective study could confirm these results.

Comparative Analysis of PEG-Free and PEG-Based Self-Emulsifying Drug Delivery Systems for Enhanced Oral Bioavailability of Therapeutic (Poly) Peptides.

This study aims to compare the potential of Polyethylene glycol (PEG-free and PEG-based self-emulsifying drug delivery systems (SEDDS) for the oral administration of insulin glargine (IG). Hydrophobic ion pairs (HIPs) of IG are formed using various counterions. HIPs are assessed for log P octanol/water and dissociation behavior. They are incorporated into SEDDS based on polyglycerol (PG) and zwitterionic surfactant (ZW) using response surface methodology and compared to conventional PEG-SEDDS in size, stability, and log D SEDDS/release medium. Oral IG bioavailability in PG/ZW-SEDDS and PEG-SEDDS is evaluated in rats. Among the various counterions studied, IG-BIS (bis(isotridecyl)sulfosuccinate) HIPs demonstrated the highest log P and an improved dissociation profile. PG/ZW-SEDDS and PEG-SEDDS have similar ≈40nm sizes and are stable over 24 h. Both formulations have log D > 4 in water and >2 in 50mM phosphate buffer pH 6.8. PG/ZW-SEDDS yielded an oral bioavailability of 2.13 ± 0.66% for IG, while the employment of PEG-SEDDS resulted in an oral bioavailability of 1.15 ± 0.35%. This study highlights the prospective utilization of PEG-free SEDDS involving the concurrent application of PG and ZW surfactants, an alternative to conventional PEG surfactants, for improved oral therapeutic (poly) peptide delivery.

Se-Glargine: Chemical Synthesis of a Basal Insulin Analogue Stabilized by an Internal Diselenide Bridge.

Insulin has long provided a model for studies of protein folding and stability, enabling enhanced treatment of diabetes mellitus via analogue design. We describe the chemical synthesis of a basal insulin analogue stabilized by substitution of an internal cystine (A6-A11) by a diselenide bridge. The studies focused on insulin glargine (formulated as Lantus® and Toujeo®; Sanofi). Prepared at pH 4 in the presence of zinc ions, glargine exhibits a shifted isoelectric point due to a basic B chain extension (ArgB31 -ArgB32 ). Subcutaneous injection leads to pH-dependent precipitation of a long-lived depot. Pairwise substitution of CysA6 and CysA11 by selenocysteine was effected by solid-phase peptide synthesis; the modified A chain also contained substitution of AsnA21 by Gly, circumventing acid-catalyzed deamidation. Although chain combination of native glargine yielded negligible product, in accordance with previous synthetic studies, the pairwise selenocysteine substitution partially rescued this reaction: substantial product was obtained through repeated combination, yielding a stabilized insulin analogue. This strategy thus exploited both (a) the unique redox properties of selenocysteine in protein folding and (b) favorable packing of an internal diselenide bridge in the native state, once achieved. Such rational optimization of protein folding and stability may be generalizable to diverse disulfide-stabilized proteins of therapeutic interest.

Efficacy and safety of tirzepatide in people with type 2 diabetes by baseline body mass index: An exploratory subgroup analysis of SURPASS-AP-Combo.

To assess the efficacy and safety of tirzepatide versus insulin glargine in people with type 2 diabetes (T2D) by baseline body mass index (BMI). Participants with T2D from the Phase 3 SURPASS-AP-Combo trial (NCT04093752) were categorized into three BMI subgroups (normal weight [<25 kg/m2 ], overweight [≥25 and <30 kg/m2 ], and obese [≥30 kg/m2 ]) according to World Health Organization criteria. Exploratory outcomes including glycaemic control, body weight, cardiometabolic risk, and safety were compared among three tirzepatide doses (5, 10 or 15 mg) and insulin glargine. Of 907 participants, 235 (25.9%) had a BMI <25 kg/m2 , 458 (50.5%) a BMI ≥25 to <30 kg/m2 , and 214 (23.6%) a BMI ≥30 kg/m2 at baseline. At Week 40, all tirzepatide doses led to a greater reduction in mean glycated haemoglobin (HbA1c; -2.0% to -2.8% vs. -0.8% to -1.0%, respectively) and percent change in body weight (-5.5% to -10.8% vs. 1.0% to 2.5%, respectively) versus insulin glargine, across the BMI subgroups. Compared with insulin glargine, a higher proportion of tirzepatide-treated participants achieved treatment goals for HbA1c and body weight reduction. Improvements in other cardiometabolic indicators were also observed with tirzepatide across all the BMI subgroups. The safety profile of tirzepatide was similar across all subgroups by BMI. The most frequent adverse events with tirzepatide were gastrointestinal-related events and decreased appetite, with relatively few events leading to treatment discontinuation. In participants with T2D, regardless of baseline BMI, treatment with tirzepatide resulted in statistically significant and clinically meaningful glycaemic reductions and body weight reductions compared with insulin glargine, with a safety profile consistent with previous reports.

Is Tirzepatide the New Game Changer in Type 2 Diabetes?

Background: Tirzepatide (TZP) is a once-weekly glucagon-like peptide 1 (GLP-1) and glucose-dependent-insulinotropic-polypeptide (GIP) receptor co-agonist approved for T2D. TZP provides promising evidence in improving glucose control and weight loss in T2D and obesity across preclinical and human studies, including data from the SURPASS program. Aims: The goal of this paper was to review the evidence on TZP in terms of glucose control, body weight, and the progression of chronic diabetes-related complications and comorbidities. Results: The mean change in HbA1c ranged from −1.6% to −2.06% over placebo, from −0.29% to −0.92% over each GLP-1RAs, and from −0.7% to −1.09% over basal insulins. In SURPASS-6, TZP was more effective than insulin lispro U100 added to basal insulin in reducing HbA1c levels at the study end (−2.1% vs. −1.1%, respectively). Compared to placebo, TZP induces a significant weight loss: 7.5 (5 mg/week); 11 (10 mg/week); and 12 kg (15 mg/week). Compared to GLP-1RAs, TZP reduces body weight from −1.68 kg to −7.16 kg depending on the dose (5 to 15 mg, respectively). Compared to basal insulin alone rigorously titrated, TZP added onto basal-insulin results in the best strategy for the composite endpoint of improvement of glucose control and weight loss. In SURPASS-6, TZP compared to insulin lispro U100 in add-on to insulin glargine U100 reduced body weight by 9 kg in mean (versus weight gain in basal-bolus users: +3.2 kg). TZP has pleiotropic effects potentially dampening the individual cardiovascular risk, including a reduction in systolic arterial pressure by 4 to 6 mmHg and total cholesterol by 4–6% compared to baseline. A post hoc analysis of SURPASS-4 revealed that TZP, compared to glargine U100, delayed the rate of glomerular filtration decline (−1.4 mL/min vs. −3.6 mL/min, respectively), reduced the rate of urinary albumin excretion (−6.8% vs. +36.9%, respectively), and was associated with a lower occurrence of the composite renal endpoint (HR 0.58 [0.43; 0.80]). Conclusions: Consistent evidence indicates that TZP dramatically changes the clinical course of T2D in different clinical scenarios. The efficacy and safety of TZP on chronic diabetes-related comorbidities and complications seem promising, but ongoing trials will clarify the real benefits.

Comparison of efficacy and safety of insulin degludec/liraglutide and insulin glargine U-100/lixisenatide in individuals with type 2 diabetes mellitus using professional continuous glucose monitoring.

Insulin glargine U100/lixisenatide and insulin degludec/liraglutide are fixed-ratio combinations containing basal insulin and a glucagon-like peptide-1 receptor agonist capable of reducing both fasting and postprandial blood glucose levels with a single formulation. This study aimed to compare the time in range (TIR) and the time below range (TBR) level 1 using professional continuous glucose monitoring and to establish criteria for the differential use of the fixed-ratio combinations. Thirty-six outpatients with type 2 diabetes mellitus (24 men and 12 women; average age, 62.1 years) were randomly assigned to the groups. At 0 and 18 weeks, a device was worn to compare the TIR and TBR level 1. Thecorrelation between the C-peptide index at baseline and TIR at 18 weeks was assessed. The TIR and TBR level 1 showed no significant differences between the two groups. Both groups showed significant positive correlations between the C-peptide index and the TIR (P = 0.002, r = 0.679; P = 0.002, r = 0.681, respectively). The changes in glycemic variability, therapeutic indices, and body mass index were not significantly different among the groups (P > 0.05). The receiver operating curve analysis revealed that the cut-off values of the C-peptide index to achieve TIR of >70% at 18 weeks were 1.258 (sensitivity, 77.8%; specificity, 100%) and 1.099 (sensitivity, 57.1%; specificity, 90.9%) in the insulin glargine U100/lixisenatide and insulin degludec/liraglutide groups, respectively. A TIR of >70% was achieved for both fixed-ratio combinations without significant differences.

Efficacy and safety of insulin glargine 300 units/mL vs insulin degludec in patients with type 1 and type 2 diabetes: a systematic review and meta-analysis.

Ultra-long-acting insulin analogs [insulin degludec (IDeg) and insulin glargine 300 units/mL (IGla-300)] offer a longer duration of action with less risk of hypoglycemia compared to other long-acting insulins. However, data about the comparative efficacy and safety are inconsistent. We searched CENTRAL, PubMed, Embase, ICTRP Search Portal, and ClinicalTrials.gov on 7 October 2022. Randomized controlled trials (RCTs) comparing the safety and efficacy of IDeg (100 or 200 units/mL) and IGla-300 in patients with type 1 or type 2 diabetes were included. Three review authors independently selected trials, assessed the risk of bias, extracted data, and evaluated the overall certainty of the evidence using GRADE. The primary outcomes were the change in glycated hemoglobin (HbA1c) and any hypoglycemia; the secondary outcomes were the change in fasting plasma glucose (FPG) and severe and nocturnal hypoglycemia. Four open-label RCTs were included (2727 participants), 3 parallel and 1 cross-over. Overall, the risk of bias assessment yielded some concern or high risk. There was a comparable change in HbA1c from baseline to the end of treatment, a mean difference of 0.07% (95% confidence interval (CI) 0.06 - 0.19; p = 0.29; 3 trials; 2652 patients; very low-certainty evidence), and a comparable rate of any hypoglycemia, rate ratio 1.02 (95% CI 0.8 - 1.3; p = 0.87; 3 trials; 2881 patients; very low-certainty evidence). IDeg resulted in more reduction in FPG compared to IGla-300, mean difference of 10.27 mg/dL (95% CI 7.25 - 13.29; p < 0.001; 3 trials; 2668 patients; low-certainty evidence). Similar rates of nocturnal and severe hypoglycemia were observed, rate ratio of 1.13 (95% CI 0.72 - 1.78; p = 0.54; 3 trials; 2668 patients; very low-certainty evidence) and 1.4 (95% CI 0.41 - 4.73; p = 0.59; 2 trials; 1952 patients; very low-certainty evidence), respectively. There is no evidence of a difference between IDeg and IGla-300 in the mean change in HbA1c and the risk of anytime, nocturnal, and severe hypoglycemia. IDeg appeared to cause a higher reduction in FPG compared to IGla-300. However, this finding should be interpreted with caution due to the small number of trials included and their high risk of bias. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022364891, identifier CRD42022364891.

P-32 A Seckel syndrome patient exhibited with metabolic problems

Abstract Introduction Seckel syndrome is a disease with nine distinct phenotypes that is inherited autosomally recessively and is caused by DNA damage on chromosomes 3, 13, and 18. It is also known as 'bird-headed dwarfism' due to the disease's characteristic phenotypic features, microcephaly and dwarfism. In addition to mental retardation, other possible complications include bilateral optic atrophy, strabismus, hearing difficulties, micrognathia, microdontia, hypodontia, malocclusion of the mandible, scoliosis, bone anomalies, hematological, endocrinological, genitourinary, neurological anomalies (epilepsy, etc.), and cancers. Presented here is a patient with metabolic dysfunction who has been diagnosed with Seckel's syndrome. Clinical Case A male patient, age 22, was admitted to the endocrinology outpatient clinic for regulation of hyperglycemia. The patient's medical history included diabetes of type 2 since 2021, hypothyroidism, mental retardation, and hepatosteatosis. His parents were related as first cousins. One of the patient's two brothers has been diagnosed with Seckel syndrome. On his physical examination, his temperature was 36.1°C, his blood pressure was 92/61 mmHg, his heart rate was 76 beats per minute, his height was 125 cm, his weight was 19 kg, and his BMI was 12 kg/m2. Microcephaly, hypodontia, and micrognotia were observed. The patient was using insulin glargin 32 units, insulin aspart 2×18 units, metformin 500mg once day, and levothyroxine sodium 50mcg. In blood glucose follow-ups, the highest was 304 mg/dl and the lowest was 127 mg/dl, whereas Hba1c was 7.5% and c-peptide was 2.44 ng/ml. Anti-GAD, anti-islet cell, anti-TPO, and antithyroglobulin antibodies were negative. Insulin glargine was changed to 34 units, and insulin aspart was changed to 2×20 units. Due to mental retardation and hypodontia, it was discovered that the patient could not pay attention to his diet, could hardly eat solid foods, and was provided primarily liquids, particularly sugar-sweetened, flavored, and carbonated soft drinks. The patient was referred to the dental polyclinic and dietitian, while the family was monitored at the genetics polyclinic. Conclusion Follow-up care for patients with Seckel syndrome should include routine metabolic screening. Due to the patient's mental cooperation and dietary habits resulting from dental anomalies, metabolic control may be challenging. To ensure metabolic homeostasis in these patients, a multidisciplinary approach is necessary, involving the patient, his or her family, in multidisciplinary setting.

P-33 A rare form of diabetes: MELAS

Abstract Introduction MELAS (mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes) is a fatal multisystemic condition caused by a mitochondrial DNA mutation, the most prevalent is m.3243AAG. Diagnosis is common at a young age,and individuals with late diagnosis due to comorbidities have a shorter life expectancy. It causes dementia, epilepsy, myopathy, hearing loss, diabetes, and growth retardation. We present a patient with MELAS who was diagnosed late since it is a rare manifestation of diabetes with a different treatment than regular diabetes. Clinical Case A fifty-year-old female patient requested regulation of her blood sugar. She had type 2 diabetes for 20 years and hypertension, hyperlipidemia; she had a coronary bypass surgery three years ago and had been using a hearing implant for one year. She is under insulin treatment since 2018. Her 13-year-old daughter was just diagnosed with MELAS due to growth and development delays, and the m.3243AG mutation was discovered. She also screened for MELAS and found heteroplasmic m.3243A&amp;lt;G mutation. Her height was 143 cm, weight was 38 kg and BMI was 18.5 kg/m2. The patient was oriented and cooperative, but reluctant to answer questions. Her speech was slow, she was partial numbness, and she was not open to communication due to hearing loss, questions were always answered by her daughter. She exhibited a poor memory and calculation functions. She had muscle weakness in both extremities with a proximal muscles strength level of 3 and also described exercise intolerance. The patient did not have any seizures. She described a loss of hearing in the left ear and very poor hearing in the right ear. She had attacks of a migraine-like headache in left side of head and palpitation. Her medications included insulin glargine 1×22 units, insulin glulisine 3×8 units, coenzyme Q10 2×100 mg, arginine 3×2.5 grams, ranolazine 375 mg, perindopril 5 mg, sprinolactone 25 mg, metoprolol 50 mg, and rosuvastatin 20 mg. While Hba1c was 10.4 µg/dl, there were postprandial hyperglycemias with the highest 372 mg/dl and fasting hypoglycemias with the lowest 55 mg/dl in blood sugar follow-ups. The patient's treatment was arranged as 2×15 units of insulin degludec aspart and 1×8 units of insulin glulisine before lunch. Linagliptin was preferred instead of the weight-loss GLP-1 agonist to reduce mitochondrial stress in the patient with low BMI. Diabetic oral nutrition therapy was recommended to the malnourished patient. For cardiac evaluation, echocardiography and rhythm holter were requested. The patient was referred to the dementia outpatient clinic for memory and poor higher neurological function. Our patient had late diagnosis of MELAS with multiple complications including sensorineural deafness, a short stature and neurologic manifestations. Considering MELAS in diabetic patients with hearing loss, neurodegenerative findings, low body mass index and intolerant of metformin will significantly reduce the morbidity of the disease by enabling early diagnosis and treatment.

Effectiveness and Safety of Initiation and Titration of Insulin Glargine 300 U/mL in Insulin-Naive Patients with Type 2 Diabetes Mellitus Uncontrolled on Oral Antidiabetic Drug Treatment in Turkey: The EASE Study

Effectiveness and Safety of Initiation and Titration of Insulin Glargine 300 U/mL in Insulin-Naive Patients with Type 2 Diabetes Mellitus Uncontrolled on Oral Antidiabetic Drug Treatment in Turkey: The EASE Study

Improvement of blood glucose control and reduction of hypoglycemia, body weight, and C-reactive protein in type 1 diabetic patients treated with intensive insulin therapy with insulin analogs

Background/Aim. Good metabolic control can delay the onset and progression of chronic complications of diabetes mellitus (DM). Intensified insulin therapy (IIT) is the cornerstone of good metabolic control in the treatment of type 1 DM (T1DM) while avoiding hypoglycemia and body weight (BW) gain in those patients. The aim of the study was to assess the effects of IIT with insulin analogs (aspart and glargine) in T1DM patients. Methods. This prospective clinical study included 49 patients with at least one year of T1DM duration, who were on IIT with human insulin at that moment. They commenced therapy with insulin aspart for three months, followed by insulin glargine for another three months. An analysis of blood glucose (BG) control (glycated hemoglobin ? HbA1c, mean BG, fasting BG, postprandial BG, and glycemic variability) and analysis of BW, hypoglycemia, and C-reactive protein (CRP) levels were performed. Results. The HbA1c level decreased slightly (non-significantly) after three months of insulin aspart therapy (from 9.28% to 8.83%) and decreased significantly after the aspart/glargine combination (to 8.08%; p &lt; 0.001). After the first three months with aspart therapy, a significant reduction in postprandial BG was noted after all three main meals. The mean postprandial rise of BG was significantly reduced. The variability of daily BG was significantly reduced (standard deviation of BG fell from 2.28 mmol/L to 1.90 mmol/L; p &lt; 0.05). The mean BG value in the profiles decreased (from 9.11 mmol/L to 8.31 mmol/L; p &lt; 0.05). All BG values in the profiles after six months were statistically significantly lower compared to the initial values, as well as the mean BG (6.88 mmol/L; p &lt; 0.001) and the variability of daily BG (1.49 mmol/L; p &lt; 0.01). Our results showed a significant reduction in the number of hypoglycemias after three months, especially after the introduction of insulin glargine therapy (significant reduction in the number of symptomatic, asymptomatic, and nocturnal hypoglycemias). The results showed a discrete but significant reduction in BW and a significant reduction in CRP levels (from 3.43 mg/L to 2.25 mg/L; p &lt; 0.001). Conclusion. Treatment of patients with T1DM with insulin analogs (insulin aspart and insulin glargine) in IIT leads to improved BG control with a reduction in the number of hypoglycemia, BW, and CRP levels.

Increasing the production of insulin glargine in Pichia pastoris through medium modification

Increasing the production of insulin glargine in <i>Pichia pastoris</i> through medium modification

Effect of Overlapping Insulin Glargine Administration in Decreasing Incidence of Hyperglycemia after Discontinuation of Intravenous Insulin Infusion

Effect of Overlapping Insulin Glargine Administration in Decreasing Incidence of Hyperglycemia after Discontinuation of Intravenous Insulin Infusion

Once-weekly Insulin Icodec Versus Once-daily Long-acting Insulin for Type II Diabetes: A Meta-analysis of Randomized Controlled Trials.

Insulin icodec is a novel basal insulin analog with once-weekly subcutaneous administration. We aim to estimate the efficacy and safety of insulin icodec vs long-acting insulin (insulin glargine and degludec) in type II diabetic patients. We conducted a systematic review and meta-analysis synthesizing randomized controlled trials (RCTs), which were retrieved by systematically searching PubMed, Web of Science, SCOPUS, and Cochrane through May 29, 2023. We used RevMan V. 5.4 to pool dichotomous data using risk ratio (RR) and continuous data using mean difference (MD) with a 95% confidence interval (CI). Our primary outcome was glycated hemoglobin (HbA1C) change. We included 7 RCTs with a total of 3183 patients. Insulin icodec was associated with significantly decreased HbA1C (MD: -0.15 with 95% CI [-0.24, -0.06], P = .002) and increased percentage of time with glucose in range (TIR) (MD: 4.06 with 95% CI [2.06, 6.06], P = .0001). However, insulin icodec was associated with increased body weight (MD: 0.57 with 95% CI [0.45, 0.70], P = .00001). Also, there was no difference regarding any serious adverse events (AEs) (RR: 0.96 with 95% CI [0.76, 1.20], P = .7) or AEs leading to withdrawal (RR: 1.54 with 95% CI [0.84, 2.82], P = .16). However, insulin icodec was associated with increased any AEs incidence (RR: 1.06 with 95% CI [1.01, 1.12], P = .02). Insulin icodec was associated with decreased HbA1C, increased TIR, with similar hypoglycemic and serious AEs. However, it was also associated with increased body weight and the incidence of any AEs.

A retrospective electronic medical record-based study of insulin usage and outcomes in insulin-naive Indian adults with T2DM: The REALITY study

ObjectiveThis retrospective longitudinal study analyzed the demographic profile, insulin usage pattern, and outcomes of insulin-naive adults with type 2 diabetes mellitus (T2DM) who initiated insulin glargine.MethodsThe study included 1006 insulin naive T2DM individuals aged ≥ 18 years, treated with any insulin type between January 2016 and December 2018, using electronic medical records.ResultsMajority of participants were men (55.8%) with a mean age of 59.8 ± 11.9 years and average T2DM duration of 12.0 ± 6.6 years. Insulin glargine was the most commonly used insulin (66.9%), followed by insulin aspart (16.4%), insulin degludec (15.1%), human insulin (11.1%), and insulin isophane (9.2%). At baseline, the mean glycated hemoglobin (HbA1c) was 8.9 ± 1.9%, mean fasting plasma glucose (FPG) was 190 ± 59 mg/dL, and mean post-prandial plasma glucose (PPG) was 264 ± 78 mg/dL. In the insulin glargine group, baseline HbA1c was 9.0 ± 1.7%, FPG was 196 ± 62 mg/dL, and PPG was 283 ± 81 mg/dL. Throughout the study, there was an improvement in HbA1c, FPG, and PPG levels in the insulin glargine group. Body weight remained relatively stable, and the number of hypoglycemic events was minimal and non-life-threatening.ConclusionThe REALITY study in India demonstrated that initiating basal insulin treatment in insulin-naive individuals with T2DM led to improved glycemic parameters over a 12-month period.

Detection of recombinant Pichia pastoris producing glargine

The global prevalence of diabetes continues to rise. Diabetes management involves the administration of insulin to help regulate blood glucose levels. Currently, two main types of insulin are used for diabetes treatment: human insulin and insulin analogs. One such insulin analog is insulin glargine, categorized as a long-acting insulin. Four prominent organisms used for insulin production are Escherichia coli, Pichia pastoris, Saccharomyces cerevisiae, and Hansenula polymorpha. Pichia pastoris was used to produce insulin glargine in this study. The pPICZαA-G plasmid containing the synthetic glargine gene was inserted into Pichia pastoris. Recombinant Pichia pastoris containing the pPICZαA-G plasmid was detected using selection media with Zeocin, Polymerase Chain Reaction (PCR), and DNA sequencing. Through the implementation of selection media containing Zeocin, PCR, and DNA sequencing techniques, it was known that the recombinant Pichia pastoris contained the synthetic glargine gene. Further research will be carried out testing the expression of glargine in recombinant Pichia pastoris.