Basal-bolus Therapy Research Articles

Clinical Evaluation of Basal-Bolus Therapy Delivered by the V-Go® Wearable Insulin Delivery Device in Patients with Type 2 Diabetes: A Retrospective Analysis.

Insulin therapy is frequently required to achieve glycemic targets (A1c) in type 2 diabetes (T2D); however, clinicians and patients face barriers with the complexities of multiple daily injection regimens. Patch-like wearable insulin devices, such as V-Go, may simplify and optimize this complexity. This study evaluated the change in A1C and insulin total daily dose (TDD) in a suboptimally-controlled (not achieving A1C targets) T2D population after switching to V-Go. A retrospective chart analysis at a diabetes clinic was performed to evaluate change in A1c measurements from baseline (V-Go initiation) to end of study observation. Of the 139 patients enrolled, A1C significantly decreased from baseline (−1.5 ± 1.79%; p < 0.001). Patients prescribed insulin at baseline (n = 122) used significantly less insulin TDD (−8 u/day; p = 0.006). The percentage of patients meeting the target of A1C < 8% increased from 14% at baseline to 48% at study completion (p = 0.008). Patients prescribed a basal-bolus regimen prior to V-Go achieved an A1C reduction of 1.5 ± 2.0% (p < 0.0001) and experienced the greatest reduction in TDD (−24 u/day; p < 0.0001). Thus, patients switching to V-Go from a variety of therapies at baseline experienced reductions in A1C while using less insulin, with a reduction in clinically relevant hypoglycemia, indicating the potential benefit of V-Go in optimizing and simplifying T2D care.

Dynamics of change in the integrated indicators of life quality and dental status of children with chronic somatic pathology at the stages of complex treatment

The increase in the incidence of type 1 diabetes mellitus in the child population over the past decades and the lack of adequate control of the disease dictate the advisability of a comprehensive study of the quality of life of this category of patients. Assessment of the quality of life complements a comprehensive medical examination and allows the most complete assessment of the child’s health, to develop rational approaches to therapy and rehabilitation. The quality of life was studied in 119 adolescents with type 1 diabetes mellitus and the duration of the disease from one to twelve years. The control group consisted of 83 practically healthy adolescents, matched by sex and age. We used the PedsQL 4.0 Pediatric Quality of Life Questionnaire for children aged 13 to 18 years: general (Generic Core Scales) and special (Diabetes Module) modules. For non-drug correction of microvascular disorders in the periodontium, in addition to traditional treatment (basal-bolus insulin therapy and symptomatic therapy), magnetic laser therapy and enzyme therapy were prescribed. it was found that the self-assessment of the quality of life of healthy children, as well as those with type 1 diabetes mellitus, exceeds the indicators of the parents’ assessment. When assessing the quality of life in adolescents with type 1 diabetes mellitus, the achievement of target glycemic indicators was noted, which is associated with control by parents, as well as self-discipline and personal manifestations of responsibility? The effectiveness of the proposed schemes of pharmaco-physiotherapeutic action in combination with basic-bolus insulin therapy and symptomatic therapy in children with different experience with type 1 diabetes mellitus has been proven by consistently stable quality of life indicators, especially in the scales «Problems associated with treatment 1» and «Problems associated with treatment 2,».

Эффективность различных прандиальных регуляторов у пациентов с сахарным диабетом 2 типа и морбидным ожирением

The choice of hypoglycemic therapy in patients with morbid obesity remains the urgent problem. At the same time, studies evaluating the features of treatment of diabetes in such patients have not yet been conducted. In this regard, an open prospective randomized study of the effectiveness of various drugs, mainly with prandial hypoglycemic effect in combination with basal insulin in patients with type 2 diabetes and morbid obesity was initiated. The study involved 141 patients. The first group received glucagon-like peptide 1 receptor agonist in combination with Metformin and basal insulin. In the second group, in addition to basal insulin and Metformin, the sulfonylurea drug was added. The third group used traditional basal-bolus therapy with Metformin. Initially and after 24 weeks of the study, all participants underwent the hospital examination, which included the determination of anthropometric indicators (height, body weight, waist circumference) and indicators of carbohydrate metabolism (fasting glucose, postprandial glycaemia, glycated hemoglobin). In addition, the frequency of hypoglycemia was assessed. It was found that in patients with type 2 diabetes and morbid obesity, the drug of choice as prandial component of treatment is the agonist of the glucagon-like peptide 1 receptor, possibly due to pleiotropic effects. In general, taking into account the presence of the complex of comorbid conditions in such patients, the ongoing hypoglycemic therapy should be personalized

Safe and Sufficient Glycemic Control by Using a Digital Clinical Decision Support System for Patients With Type 2 Diabetes in a Routine Setting on General Hospital Wards.

The aim was to investigate the applicability of a clinical decision support system in a real-world inpatient setting for patients with type 2 diabetes on general hospital wards.A total of 150 patients with type 2 diabetes requiring subcutaneous insulin therapy were treated with basal-bolus insulin therapy guided by a decision support system (GlucoTab) providing automated workflow tasks and suggestions for insulin dosing to health care professionals.By using the system, a mean daily blood glucose (BG) of 159 ± 32 mg/dL was achieved. 68.8% of measurements were in the target range (70 to <180 mg/dL). The percentage of BG values <40, <70, and ≥300 mg/dL was 0.02%, 2.2%, and 2.3%, respectively. Health care professionals' adherence to suggested insulin doses and workflow tasks was high (>93% and 91%, respectively).The decision support system facilitates safe and efficacious inpatient diabetes care by standardizing treatment workflow and providing decision support for basal-bolus insulin dosing.

Effect of the FreeStyle Libre™ flash glucose monitoring system on glycemic control in individuals with type2 diabetes treated with basal-bolus insulin therapy: An open label, prospective, multicenter trial in Japan.

Aims/IntroductionWe investigated the effect of FreeStyle LibreTM on glycemic control in Japanese type 2 diabetes patients treated with basal–bolus insulin therapy.Materials and MethodsThis prospective, 90‐day single‐arm study enrolled 94 adults with type 2 diabetes treated with insulin. A 14‐day masked baseline phase was followed by an 11‐week treatment phase during which participants used the device to monitor glucose levels. The primary end‐point was time spent in hypoglycemia (<70 mg/dL) for baseline versus study end (days 76–90). Secondary end‐points included other measures of glycemic control, along with patient satisfaction using the Japanese Diabetes Treatment and Satisfaction Questionnaire.ResultsTime spent in hypoglycemia was low at baseline (0.51 ± 0.93 h/day) and did not significantly decrease at study end (0.47 ± 0.63 h/day, P = 0.6354). Time in range, time in hyperglycemia and estimated A1c all improved versus baseline (by +1.7 ± 3.0 h/day, −1.6 ± .4 h/day and −0.4 ± 0.8%, respectively, P < 0.0001 in each). Finger stick tests fell from 2.9 ± 1.3 to 1.9 ± 1.4/day, and mean scanning frequency during the intervention phase was 11.3/day. The mean treatment satisfaction score increased by 11.8 ± 5.3 (P < 0.0001). Two severe hypoglycemia‐related adverse events were reported; one of which was possibly related to the device. Three participants reported mild device‐related skin trauma, site discomfort or subcutaneous bleeding.ConclusionsUse of FreeStyle Libre by Japanese type 2 patients diabetes treated with basal–bolus insulin therapy showed a low baseline of hypoglycemia, and enabled improved glycemic control and treatment satisfaction.

Basal insulin ameliorates post-breakfast hyperglycemia via suppression of post-breakfast proinsulin/C-peptide ratio and fasting serum free fatty acid levels in patients with type 2 diabetes.

In general, basal insulin targets fasting plasma glucose (FPG) levels, and prandial insulin targets postprandial glucose (PPG) levels. However, the effects of basal insulin on PPG levels are controversial. We investigated the effect of basal insulin on postprandial hyperglycemia using a test meal at breakfast as well as compared differences between degludec and glargine. A total of 20 participants with type 2 diabetes were randomly assigned to degludec (n = 10) or glargine (n = 10). We initiated basal-bolus insulin therapy and titrated only basal insulin until FPG was < 6.1mmol/L. We evaluated changes in post-breakfast glucose levels and changes in clinical parameters such as serum C-peptide (CPR), proinsulin (PI), and free fatty acids (FFA) levels between the pre- and post-titration periods. Differences between degludec and glargine in the post-titration period were also evaluated. Post-breakfast glucose levels significantly decreased by 46.1% in the post-titration period compared with the pre-titration period (n = 20, p < 0.001). These decreases correlated positively with decreases in the post-breakfast PI/CPR ratio (r = 0.692, p < 0.001) and in fasting FFA levels (r = 0.720, p < 0.001). There were no significant differences in post-breakfast glucose levels between degludec and glargine. However, the hypoglycemic rate with degludec was significantly lower than with glargine. Our results suggest that basal insulin with either degludec or glargine decreases the incidence of post-breakfast hyperglycemia accompanied by decreasing the post-breakfast PI/CPR ratio and fasting FFA levels in patients with type 2 diabetes.

Basal-Bolus Insulin Regimen for Hospitalised Patients with COVID-19 and Diabetes Mellitus: A Practical Approach.

Background and AimThe coronavirus disease 2019 (COVID-19) outbreak has rapidly crossed international boundaries and placed increasing demands on healthcare facilities worldwide. Patients with diabetes and uncontrolled blood glucose levels are at increased risk for poor clinical outcomes and in-hospital mortality related to COVID-19. Therefore, achieving good glycaemic control is of paramount importance among hospitalised patients with COVID-19. Basal-bolus insulin therapy is a safe and effective intervention for the management of hyperglycaemia in hospitalised patients. The aim of this article is to provide a practical guidance for the use of the basal-bolus insulin regimen in hospitalised patients with COVID-19 and diabetes mellitus.MethodsThis guidance document was formulated based on the review of available literature and the combined personal experiences of the authors. We provide a comprehensive review on the use of the basal-bolus insulin regimen, including its principles, rationale, indications, prerequisites, initiation, and dose titration, and also suggest targets for blood glucose control and different levels of capillary blood glucose monitoring. Various case scenarios are used to illustrate how optimal glucose control can be achieved, such as through adjustments in doses of prandial and basal insulin, the use of correctional insulin dosing and changes in the timing and content of major and minor meals.ConclusionThe practical guidance for the use of the basal-bolus insulin regimen in hospitalised patients with COVID-19 and diabetes mellitus presented here can be used for patients admitted to hospital for indications other than COVID-19 and for those in ambulatory care.Electronic supplementary materialThe online version of this article (10.1007/s13300-020-00873-3) contains supplementary material, which is available to authorized users.

91-LB: Study of Glycemic Variability and Hypoglycemia Using Continuous Glucose Monitoring in Type 2 Diabetes Mellitus Changed from Basal-Bolus Therapy to Basal-GLP-1RA Therapy

Background and Aims: There are currently nine categories of hypoglycemic drugs and the range of choice is expanding. Insulin is very effective but prone to hypoglycemia. Therefore, it is important to consider changing to drugs that are unlikely to cause hypoglycemia in patients who have stable glycemic status. At the same time, however, it should be noted that inappropriate de-escalation of treatment leads to a worsening of the glycemic situation. Thus, in patients with T2D treated with Basal-Bolus Therapy (BBT) using a small amount of bolus insulin and stable glycemic control, under CGM, we had left basal insulin and switched from all bolus insulin to a weekly GLP-1 RA. Materials and Methods: The subjects were T2D outpatients who were changed from BBT to Basal-GLP-1 RA Therapy (BGT) under CGM during the period from November 2018 to November 2019. Freestyle Libre Pro was used as CGM in all cases. We analyzed average glucose levels, glycemic variability (%CV), Time Below Range (&amp;lt;70mg/dl), Time In Range (70-180 mg/dl) for 3 days before and after treatment change. A total of 18 patients were included in this study. On average, the patient group was aged 58 years and they had been living with T2D for the past 7.0 years. Their HbA1c was 6.6% and BMI was 25.9 kg/m2. Non-fasting CPR was 2.9 ng/ml. Total daily bolus insulin dose was 12.6 units. Results: In all cases, bolus insulin was changed to dulaglutide 0.75mg with the same amount of basal insulin. There was no deterioration in mean glucose levels, TBR and TIR (115.4 vs. 105.7 mg/dl, 8.2 vs. 7.5%, 81.4 vs. 87.6%, respectively). %CV (21.1 vs. 15.7%; P = 0.029) and HbA1c (6.6 vs. 6.3%; P = 0.020) were significantly improved. Conclusion: In T2D with stable glycemic status and maintained endogenous insulin secretion, stepping down from BBT using a small amount of bolus insulin to BGT was able to better manage glycemic level and variability under CGM observation. Disclosure A. Miyoshi: None. S. Obara: None. N. Wada: None.

1043-P: GoBolus Study: Impact of Faster Aspart on Glycemic Control in a Real-World Population with Type 1 Diabetes on Basal-Bolus Therapy as Multiple Daily Injections Using Flash Glucose Monitoring

Background and Methods: Randomized trials have shown that faster aspart (FA) improves glycemic control in patients with T1D. The German observational study GoBolus (NCT03450863) collected real-world clinical and patient-reported data of patients with T1D treated with basal/bolus therapy as multiple daily injections (MDIs), who were switched from other bolus insulins to FA by their physician. Results: Overall, 243 patients were enrolled, with a mean age of 49.9 years, mean baseline A1C of 8.1%, mean BMI of 28.1 kg/m2 and mean diabetes duration of 18.8 years: 55.6% were male. Over 24 weeks’ FA treatment, primary endpoint (A1C) decreased by 0.19% (p&amp;lt;0.01) without changes in insulin doses or basal/bolus insulin ratios. Flash glucose monitoring data (Figure) showed increased “time in range” (TIR, 3.9-10 mmol/L) from 46.9% to 50.1% (p=0.01) and decreased time in hyperglycemia (&amp;gt;10 and &amp;gt;13.9 mmol/L) from 49.1% to 46.1% (p=0.03) and 20.4% to 17.9% (p=0.01), respectively, without change for time in hypoglycemia (&amp;lt;3.9 and &amp;lt;3.0 mmol/L). Mean interstitial and 3-h postprandial glucose improved from 10.4 to 10.1 mmol/L (p=0.04) and 11.9 to 11.0 mmol/L (p&amp;lt;0.01), respectively. Conclusions: Switching bolus insulin to FA in patients with T1D on MDIs improved glycemic control, increased TIR and decreased time in hyperglycemia. Disclosure T. Danne: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Sanofi. M. Schweitzer: Employee; Self; Novo Nordisk A/S. W. Keuthage: Advisory Panel; Self; Deutschland GmbH, Novo Nordisk A/S, Roche Diabetes Care. Board Member; Self; Abbott, Berlin-Chemie AG. S. Kipper: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. Y. Kretzschmar: Employee; Self; Novo Nordisk A/S. J. Simon: None. R. Ziegler: Advisory Panel; Self; Abbott, Lilly Diabetes, Novo Nordisk A/S, Roche Diabetes Care. Consultant; Self; Novo Nordisk A/S, Roche Diabetes Care. Speaker’s Bureau; Self; Abbott, Dexcom, Inc., Novo Nordisk A/S, Roche Diabetes Care. Funding Novo Nordisk

24-OR: Electronic Decision Support for Insulin Therapy Is Safe and Efficient in Inpatients with Type 2 Diabetes

Attainment of good glycemic control in hospitalized patients with type 2 diabetes (T2D) is often hampered by fear of hypoglycemia and insufficient knowledge in insulin therapy. An electronic algorithm-based decision support system (GlucoTab®, decide Clinical Software GmbH, Graz, Austria) for inpatient management was developed and has proven efficacy in clinical trials. After implementing GlucoTab® in routine care, a retrospective analysis of T2D patients requiring subcutaneous insulin therapy on an Endocrinology ward was performed. Data from days when patients received algorithm-steered basal-bolus insulin therapy (BBI) was compared with days when insulin therapy was performed according to local standard care (SC) provided by an endocrinologist. As the treating physician was free to start/stop decision support during inpatient stay, patients switched between BBI and SC. During the first six months following GlucoTab® implementation, a total of 71 T2D patients required subcutaneous insulin therapy and subsequently were included in this analysis. Incomplete treatment days (e.g., admission and discharge days; days, where both therapy schemes applied) were excluded, resulting in 261 BBI and 274 SC days. Baseline characteristics were as follows: 39 % women, 99 % Caucasian, age 73.5 ± 12.5 years, diabetes duration 15.4 ± 10.6 years, HbA1c 70.4 ± 24.2 mmol/mol, BMI 29.0 ± 5.5 kg/m² and creatinine 1.6 ± 1.2 mg/dL. Mean daily glucose was lower for BBI vs. SC: 156.9 ± 35.7 mg/dL vs. 172.1 ± 47.3 mg/dL. Total daily insulin dose was higher for BBI vs. SC: 42.2 ± 25.2 U vs. 33.7 ± 20.9 U. Blood glucose (BG) in target (70-180 mg/dL) was higher for BBI vs. SC: 70 % vs. 61.2 %. BG &amp;lt;70 mg/dL was 1.6 % vs. 1.9 % and BG &amp;lt;54 mg/dL was 0.2 % vs. 0.6 % (BBI vs. SC, respectively). Continuous use of BBI resulted in a BG decline from 182 (day 1) to 147 mg/dL (day 10) while it remained elevated in SC (188 to 177 mg/dL). BBI showed beneficial glycemic control compared to SC in routine use during inpatient diabetes management. Disclosure D.A. Hochfellner: None. H. Ziko: None. M.H. Sagmeister: None. H. Elsayed: None. M. Cigler: None. T. Poettler: None. F. Aberer: None. G. Sendlhofer: None. P. Beck: Employee; Self; decide Clinical Software. Stock/Shareholder; Self; decide Clinical Software. J.K. Mader: Advisory Panel; Self; Becton, Dickinson and Company, Eli Lilly and Company, Medtronic, Prediktor Medical, Sanofi-Aventis. Speaker’s Bureau; Self; Abbott, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Roche Diabetes Care, Sanofi-Aventis.

1020-P: Effects of Insulin Degludec and Insulin Glargine U300 on Interday Glycemic Variability in Individuals with Type 1 Diabetes: A Multicenter, Randomized, Crossover Study

Background: Insulin degludec (IDeg) and insulin glargine U300 (IGla-300) are recently launched ultra-long-acting insulin formulations. It remains unclear whether or how their glucose-stabilizing effects differ. We now compared the effects of these insulins on parameters on glycemic variability in patients with type 1 diabetes (T1D). Methods: This multicenter, randomized, crossover, non-inferiority trial recruited 46 patients with T1D treated with basal-bolus insulin therapy at 14 facilities in Japan. Patients were randomly assigned 1:1 to IGla-300 (first period)/IDeg (second period) or IDeg (first period)/IGla-300 (second period) groups, in which subjects were treated with the corresponding basal insulin for 4-week periods. The last week of each treatment period constituted the data collection phase, during which the participants determined the plasma glucose level seven times a day using a SMBG devise and were also equipped with a CGM devise. The primary end point was comparison of day-to-day glycemic variability evaluated by the standard deviation (SD) of FPG during the last week of each treatment period. Results: The SD for FPG in the IDeg treatment period was not inferior to that in the IGla-300 treatment period (95% CI, -16.1-3.0 mg/dL). The levels (95% CI, -18.4-5.7 mg/dL) and the coefficient of variance (95% CI, -4.6-4.3 %) of FPG did not significantly differ between the two periods. Parameters obtained with CGM, including time-in-range, duration of nocturnal hypoglycemia, mean amplitude of glycemic excursion, and mean of the daily differences, as well as the doses of basal and bolus insulins also did not significantly differ between the two treatment periods. Conclusion: IDeg was not inferior to IGla-300 in terms of inter-day glycemic variability in the treatment of T1D, and the treatments with these two insulins yielded similar outcomes for various parameters related to blood glucose control. Disclosure H. Miura: None. K. Sakaguchi: Other Relationship; Self; AstraZeneca, Novartis AG, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sanwa Kagaku Kenkyusho, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. A. Kaneko: None. J. Ito: None. Y. Morita: None. T. Yamada: None. N. Otowa-Suematsu: None. A. So: None. T. Nakamura: None. H. Komada: None. Y. Okada: None. Y. Hirota: Other Relationship; Self; Sanofi. Y. Tamori: None. W. Ogawa: Research Support; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharma GmbH &amp; Co.KG, Eli Lilly Japan K.K., Kowa Company, Ltd., Nippon Boehringer Ingelheim Co. Ltd., Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Other Relationship; Self; Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited.

2191-PUB: Challenging the 50%/50% Basal/Bolus Insulin Ratio Rule: Have We Been Wrong? A Cross-Sectional Study

There is a generally-held belief that the ratio between basal and bolus insulin requirements in patients using insulin therapy should be 50%/50%. Yet, it appears this belief was based on a small study with healthy individuals, which may not be applicable to patients with insulin deficiency. To assess the validity of the rule we followed patients with type 2 diabetes treated with basal-bolus insulin therapy that has been frequently adjusted by a technology-based titration service. To keep glycemia stable, the service adjusts insulin dosage at least weekly and thus treatment closely tracks insulin requirements. We performed a cross-sectional study, accumulating data on N=306 patients over an average±SD period of 3.4±1.7 years. Insulin titrations occurred every 6.8±1.5 days to enable HbA1c maintenance at 7.2±0.7%. In 74.8% of the patients the average basal insulin fraction was less than 50% of total daily dose of insulin, and in about a third it was less than 38% (Figure). Additionally, the basal fraction did not remain stable in each patient over time (Figure). In 79.7% of the patients, it changed more than 20% and in 50% more than 29.8% (e.g., basal fraction changes in a single patient would range between 20% and 50% over time). In patients with type 2 diabetes treated with insulin, basal-bolus ratio is not 50%/50% and it changes over time. Thus, this ratio should not be used as a treatment guide. Disclosure I. Hodish: Stock/Shareholder; Self; Hygieia. M. Willis: Employee; Self; Hygieia. S. Sritharan: None. E. Bashan: Employee; Self; Hygieia. Stock/Shareholder; Self; Hygieia.

269-OR: Effect of Insulin Degludec on Frequency of Severe Hypoglycemia in Patients with Type 1 Diabetes Prone to Nocturnal Severe Hypoglycemia: The HypoDeg Trial

Background and Aims: The long-acting insulin analog degludec reduces the risk of nocturnal hypoglycemia in patients with type 1 diabetes (T1D). The HypoDeg trial compared the effect of insulin degludec to insulin glargine U100 on frequency of nocturnal hypoglycemia in T1D patients with recurrent nocturnal severe hypoglycemia and reported a significant 37% relative risk reduction (RRR) of symptomatic nocturnal hypoglycemia ≤ 3.0 mmol/L with insulin degludec. Here we report the data on severe hypoglycemia (SH). Materials and Methods: In this investigator-initiated, prospective, randomized, open-label, blinded-endpoint crossover trial conducted at 10 centers in Denmark, we recruited 149 T1D patients (&amp;gt;18 years) with ≥2 episodes of nocturnal SH in the preceding two year. Patients were randomly assigned (1:1) to basal-bolus therapy with insulin degludec and insulin aspart or insulin glargine U100 and insulin aspart. A 1-year plus 1-year treatment period was specified, consisting of two 3-month run-in periods, each followed by a 9-month maintenance period. Episodes of SH were reported by telephone and adjudicated blinded to treatment. Results: A total of 136 SH episodes were reported during the maintenance periods: 56 (41%) episodes during treatment with insulin degludec and 80 (59%) episodes during treatment with insulin glargine U100, resulting in a RRR of 35% (95% confidence interval [CI]: 0-60%; p=0.04). This corresponds to an absolute rate reduction of 0.3 episodes (95% CI: 0.0-0.5) per patient-year with insulin degludec. The difference was primarily due to a lower risk of nocturnal episodes (RRR 52%, 95% CI: -10-80%; p=0.08), whereas there was no difference during daytime (RRR 10%, 95% CI: -80-50%; p=0.75). Conclusion: Treatment with insulin degludec in T1D patients with recurrent nocturnal SH resulted in a clinically significant reduced rate of SH compared with insulin glargine U100. Disclosure R.M. Agesen: Employee; Self; Novo Nordisk A/S. A. Alibegovic: Employee; Self; Novo Nordisk A/S. H.U. Andersen: Advisory Panel; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. P. Gustenhoff: Advisory Panel; Self; Abbott Laboratories, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi-Aventis. T.K. Hansen: None. T. Jensen: Stock/Shareholder; Self; Novo Nordisk A/S. C.B. Juhl: None. A.K. Jensen: None. S. Lerche: None. K. Nørgaard: Advisory Panel; Self; Abbott, Medtronic. Research Support; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Medtronic, Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk Inc. H.D. Parving: None. A.L. Sørensen: None. L. Tarnow: None. B. Thorsteinsson: None. U. Pedersen-Bjergaard: Advisory Panel; Self; Novo Nordisk A/S, Sanofi. Research Support; Self; Novo Nordisk A/S. Funding Novo Nordisk A/S

The effect of glycated hemoglobin variability on the development of microvascular complications in patients with type 1 diabetes

Introduction. The results of a 25-year observational program to assess the effect of glycated hemoglobin variability on the development of microvascular complications in patients with type 1 diabetes mellitus are presented.Objective: This study aimed to evaluate the effect of glycated hemoglobin (HbA1c) variability on the development of microvascular complications in patients with type 1 diabetes mellitus (DM1) and disease duration of 25 years.Materials and methods: A retrospective analysis of the database of patients with DM1 was performed from the moment of the disease manifestation until the time of the last visit. Determination of HbA1c level is carried out using parameters certified in accordance with the National Standard for Glycohemoglobin Standardization (NGSP) or the International Federation of Clinical Chemists (IFCC). HbA1c variability was determinated by average current HbA1c, average of longitudinal HbA1c (from the manifestation to the last visit – 2019), median and maximum of difference in changes of HbA1c (median and max∆HbA1c). Statistical analysis was performed by IBM SPSS Statistics ver.22. A statistically significant difference is the value p &lt; 0.05.Results. A total of 88 patients were enrolled in this study, they were divided in 3 groups depending on the registered microvascular complications (MVC): without MVC (n = 38), isolated MVC (retinopathy or nephropathy) (n = 25) and multiple MVC (retinopathy and nephropathy) (n = 25). Clinical characteristics [median (25; 75 percentile)]: age of manifestation of DM1 is 9 years (5; 12), age of patients at the time of the last visit is 33 years (29; 35), duration of DM1 is 24 years (20; 27), body mass index 24 kg/m2 (21; 25). Medication: basal-bolus insulin therapy (n = 82) or pump insulin therapy (n = 6). The average level of longitudinal HbA1c for the three groups was: 8% (7.6; 8.9), 8.5% (7.9; 8.9), 8.6% (7.8; 10), p = 0.2. Average of current (at the time of the last visit) HbA1c – 8.2% (7.2; 9.0), 8.1% (7.5; 9.0), 8.4% (7.3; 9.7), p = 0.4. Statistically significant differences were determined in the group without complications and in the group with multiple complications between the levels of maxΔ HbA1c 2.3% (1.8; 2.8) vs 4.7% (3.2; 5.6), p &lt; 0.0001 and median Δ HbA1c 0.7% (0.6; 0.9) vs 1.4% (1; 1.7), р &lt; 0.0001. There were no statistically significant relationships between the maximum and medianΔ HbA1c in the groups without complications and in the group with isolated complications.Conclusions: Longitudinal HbA1c and current HbA1c are not associated with the development of microvascular complications. The potential role in the development of microvascular complications was determined for the maximum and median Δ HbA1c.

The effect of low dose glargine U 300 on uncontrolled type 2 diabetes mellitus. An observational study in Indian patients

Introduction. Insulin therapy plays an important role in the management of diabetes mellitus. The primary goal of insulin therapy is to achieve the best possible glycemic control without hypoglycemia. First-generation basal insulin (BI) analogues, such as insulin glargine 100 U/mL (Gla-100) and insulin detemir (IDet), provide more prolonged and stable activity than neutral protamine Hagedorn (NPH) insulin, with a lower risk of hypoglycemia. Insulin glargine 300 U/mL (glargine U 300) is a long acting basal insulin analogue approved for the treatment of diabetes mellitus. Insulin glargine 300 U/mL has a more stable and prolonged pharmacokinetic/pharmacodynamics profile than insulin glargine 100 U/mL, with a duration of glucose-lowering activity exceeding 24 h. Although the average daily insulin dose was higher, hypoglycemia episodes were lower in patients treated with Gla-300 compared with those treated with Gla-100. This is due to a more extended time action profile than Gla-100 resulting in a more stable and sustained glycemic control. The formulation of Gla-100 delivers the same amount of Insulin as Gla-300, in a third of the injection volume. It is essential to determine whether the clinical benefits of hypoglycemia reduction observed with insulin glargine in RCTs translate into a real-life clinical practice setting. Materials and methods. Fifty patients diagnosed with type 2 diabetes mellitus with uncontrolled plasma glucose levels (HbA1c of > 7.5) who were on oral hypoglycemic agents, premix insulin and basal bolus therapy were enrolled into the study and started on glargine U 300 at a dose of 0.2 IU/kg and analysed for glycemic and kidney function parameters. The patients were followed up at 3 and 6 months post treatment. Results. All glycemic control parameters decreased significantly with almost a 50% decline in both FBS and PBS from baseline to 6 months. The HbA1c decreased significantly from baseline to 3 months and 6 months post treatment by 18% and 29% respectively. All biochemical parameters were found to be statistically significant in both groups. Conclusions. In patients with uncontrolled type 2 diabetes, switching from either OHAs or insulin to Gla-300 improves glycemic control, with a low incidence of hypoglycemia. These results confirm the effectiveness and safety of Gla-300 in a real-world setting and show that Gla-300 is a suitable therapy option for patients with diabetes.

PDB29 A COST-UTILITY ANALYSIS OF SODIUM-GLUCOSE COTRANSPORTER (SGLT) 2 INHIBITORS IN ADDITION TO BASAL-BOLUS INSULIN IN THE TREATMENT OF TYPE 1 DIABETES IN THE USA USING THE PRIME DIABETES MODEL

Sodium-glucose cotransporter (SGLT) 2 inhibitors (and combined SGLT1/2 inhibitors) decrease renal glucose reabsorption, promoting glucose excretion in the urine (glucosuria). They have been shown to improve glycemic control in patients with type 2 diabetes with no increase in hypoglycemia. The aim of the present study was to use a modern model of type 1 diabetes to conduct a cost-utility analysis of adding SGLT inhibitors to basal-bolus insulin therapy in the US. The PRIME Diabetes Model (PRIME) was used to evaluate the cost-utility of adding SGLT inhibitors to basal-bolus insulin, adopting the perspective of a comprehensive US healthcare payer over a 60-year time horizon. Treatment effects were taken from a recent meta-analysis, and cohort characteristics were based on an SGLT1/2 inhibitor trial including data collected at 33 US sites. Quality of life utilities and US-specific costs were identified from the literature and the IBM Micromedex® RED BOOK® database, with costs expressed in 2018 US dollars (USD). Future costs and effects were discounted at 3% per annum and one-way and probabilistic sensitivity analyses were conducted. Adding SGLT inhibitors to basal-bolus insulin improved quality-adjusted life expectancy by 0.10 quality-adjusted life years (QALYs) to 12.26 QALYs, accompanied by an increase in lifetime costs of USD 5,363, yielding an incremental cost-utility ratio of USD 52,774 per QALY, fractionally over a willingness-to-pay (WTP) threshold of USD 50,000 per QALY, the lowest WTP threshold used by the Institute for Clinical and Economic Review. The analysis was extensively tailored to the US setting, with the model itself based in part on US clinical data, populated with US-specific drug cost, complication cost and mortality data. Based on data from a recent meta-analysis, addition of SGLT inhibitors to basal-bolus insulin in patients with T1D would be borderline cost-effective from a comprehensive US healthcare payer perspective.

Insulin degludec/liraglutide in type 2 diabetes: a profile of its use

Subcutaneous insulin degludec/liraglutide (Xultophy™) is a titratable, fixed-ratio combination of a long-acting insulin analogue and a glucagon-like peptide-1 receptor agonist (GLP-1RA) that is approved in several countries, including the USA and those in the EU for the treatment of type 2 diabetes (T2D) as add-on therapy. In clinical and real-world studies in insulin-naive or -experienced adults with inadequately controlled T2D, once-daily insulin degludec/liraglutide as add-on therapy to oral antidiabetic drugs consistently provided effective and durable glycaemic control, and delayed the time to treatment intensification. It also reduced the risk of hypoglycaemia and bodyweight gain compared with basal or basal-bolus insulin therapy. Insulin degludec/liraglutide is generally well tolerated and offers the convenience of once-daily administration of two injectable antidiabetic drugs.

The Benefit of Insulin Degludec/Liraglutide (IDegLira) Compared With Basal-Bolus Insulin Therapy is Consistent Across Participant Subgroups With Type 2 Diabetes in the DUAL VII Randomized Trial.

Insulin degludec/liraglutide (IDegLira) results in glycated hemoglobin (HbA1c) levels comparable with basal-bolus (BB) therapy. Here, we assessed the effect of once-daily IDegLira compared with BB (once-daily insulin glargine 100 U/mL and insulin aspart ≤4 times/day) across subgroups with varying characteristics. DUAL VII trial participants (type 2 diabetes [T2D], HbA1c 53-86 mmol/mol [7.0%-10.0%]) were subgrouped post hoc based on the following baseline characteristics: HbA1c (≤58.5, >58.5 to ≤69.4, and >69.4 mmol/mol; ≤7.5%, >7.5 to ≤8.5%, and >8.5%), body mass index (<30, ≥30 to <35, and ≥35 kg/m2), age (18 to <65 and ≥65 years), duration of diabetes (≥0 to 10 and ≥10 years), total pretrial daily basal insulin dose (20 to <30, ≥30 to <40, and ≥40 to ≤50 U), and fasting plasma glucose (<7.2 mmol/L/<130 mg/dL and ≥7.2 mmol/L/≥130 mg/dL). Compared with BB, and in all subgroups, IDegLira treatment consistently gave similar HbA1c reductions, less severe or blood glucose-confirmed hypoglycemia, lower end-of-trial (EOT) total daily insulin dose, and weight loss. In all subgroups, mean EOT HbA1c was ≤53 mmol/mol (≤7.0%). The greatest HbA1c reduction occurred in the highest baseline HbA1c subgroup. Overall, mean EOT daily insulin dose was 0.43 to 0.52 U/kg with IDegLira and 0.74 to 1.07 U/kg with BB. More participants achieved the triple composite endpoint (HbA1c <53 mmol/mol [<7.0%] without weight gain or hypoglycemia) with IDegLira vs BB across the baseline HbA1c subgroups (≤58.5 mmol/mol [44.6% vs 7.0%], >58.5 to ≤69.4 mmol/mol [41.1% vs 8.3%], and >69.4 mmol/mol [23.8% vs 3.4%]). These results support initiating IDegLira in patients with varying baseline characteristics and uncontrolled T2D on basal insulin. NCT02420262.

High prevalence of impaired awareness of hypoglycemia and severe hypoglycemia among people with insulin-treated type 2 diabetes: The Dutch Diabetes Pearl Cohort

ObjectivePeople with type 2 diabetes on insulin are at risk for hypoglycemia. Recurrent hypoglycemia can cause impaired awareness of hypoglycemia (IAH), and increase the risk for severe hypoglycemia. The aim...

Insulin Glargine 300U/mL and Insulin Glulisine Treatment in Patients with Type2 Diabetes: A Non-Interventional Study of Effectiveness in Routine Clinical Practice.

IntroductionThe EDITION development program confirmed that insulin glargine 300 U/mL (Gla-300) provides comparable glycemic control to insulin glargine 100 U/mL (Gla-100) but with lower hypoglycemia risk. Our study aimed to evaluate the effectiveness of Gla-300 in everyday practice.MethodsThis one-arm, non-interventional study included patients with type 2 diabetes who were switched to Gla-300-based basal-bolus therapy (BBT) and followed for 6 months. Indications for switching included inadequate glycemic control and/or hypoglycemic events with the previous regimen.ResultsOverall 229 patients were included, with mean age of 60.9 years. All glycemic variables improved between baseline and 6 months significantly (mean ± standard deviation [SD] hemoglobin A1c [HbA1c] from 8.9 ± 1.5% to 7.5 ± 1.1%, fasting blood glucose from 9.5 ± 3.1 mmol/L to 7.0 ± 2.1 mmol/L, postprandial blood glucose from 12.0 ± 3.8 mmol/L to 8.9 ± 2.5 mmol/L). Gla-300 doses were increased and mealtime insulin doses were unchanged. Rates of both non-severe and severe hypoglycemic events decreased significantly compared to pre-study and 6-month follow-up periods. Patients switched because of elevated HbA1c had higher baseline HbA1c and greater decrease in HbA1c paralleled with increase in insulin doses compared to those switched because of hypoglycemia.ConclusionsIn day-to-day practice, switching from human insulin to Gla-300-based BBT resulted in significant improvement in glycemic control and decrease in hypoglycemia risk.