Basal-bolus Insulin Therapy Research Articles

BASal-bolus Insulin therapy in Critically ill patients (BASIC): A randomized controlled trial protocol

BASal-bolus Insulin therapy in Critically ill patients (BASIC): A randomized controlled trial protocol

Cost-utility analysis of once-weekly insulin icodec and once-daily insulin glargine in patients with type 2 diabetes receiving basal-bolus insulin therapy in China.

The purpose of this study is to explore the rational pricing range for the once-weekly administration of insulin icodec in the treatment of type 2 diabetes patients in China who have already received basal insulin therapy. The data foundation of this study originates from the ONWARDS 4 clinical trial and research materials on Chinese type 2 diabetes patients. By comprehensively applying cost-utility analysis methods and binary search techniques, the appropriate price positioning of insulin icodec was determined from the perspective of China's healthcare system. In the long-term treatment simulation, we found that insulin icodec and insulin glargine performed similarly in terms of quality-adjusted life years (QALYs), with 10.15 and 10.07 years, respectively. Although the annual cost of insulin icodec was initially assumed to be equivalent to that of insulin glargine, in-depth analysis revealed that insulin icodec may have higher cost-effectiveness potential. Further price sensitivity analysis indicated that the reasonable cost range of insulin icodec lies between $851.95 and $1358.25. After fine-tuning through univariate sensitivity analysis, this cost range was revised to $784.90 to $1145.96, a conclusion that was robustly validated in subsequent probabilistic sensitivity analysis and scenario simulations. The conclusion drawn from this study is that, with insulin glargine as the cost reference, the economic cost of insulin icodec for Chinese type 2 diabetes patients is expected to range from $784.90 to $1145.96, providing a reference basis for clinical decision-making and healthcare policy formulation.

Exploring the “New World”: weekly basal insulins

therapeutic option today, especially in specific clinical conditions, even in type 2 diabetes. Our country is approaching a new era in the history of insulin. We are indeed close to the availability of the first weekly basal insulin formulations. The AMD annals present a unique chance to evaluate the evolution of pharmacological therapies for diabetes in recent years. The AMD annals confirm that in 2023 still more than 32% of the population with type 2 diabetes in Italy was treated with insulin, and more than 97% of subjects were treated with basal insulin. The appropriate prescription of insulin is hindered by numerous obstacles, resulting in therapeutic inertia. Among these, the non-acceptance of daily injection therapy and the difficulty in adherence justify the rationale for developing weekly basal insulin Among the weekly basal insulins in development, icodec and efsitora are the closest to being introduced into our clinical practice. The development of new biotechnological approaches has resulted in the development of insulins with a half-life of 8 and 17 days for icodec and efsitora, respectively. Icodec and efsitora, in the QWINT and ONWARDS phase 3 programs, have been shown to be effective in achieving primary and secondary efficacy endpoints. The two weekly basal insulins have shown that in the context of an oral basal regimen for people with type 2 diabetes, the risk of hypoglycemia is not different from that of daily basal insulins In studies in type 1 diabetes and in people with type 2 diabetes on basal bolus insulin therapy, the risk of hypoglycemia was found to be higher for new weekly basal insulins than for daily basal insulins, bringing up the need for more research and possibly a different prescribing approach for basal weekly insulins in this population. The reduction in the number of injections results in patients being more satisfied with the treatment, this could result in a significant improvement in quality of life and an increase in acceptance and adherence to prescribed treatment, and finally, it responds to the urgent need to counter therapeutic inertia in the care of people with diabetes.

1867-LB: A Real-World Study Assessing the Efficacy and Safety of Switching from Basal–Bolus Insulin Therapy to Once-Daily iGlarLixi in People with Type 2 Diabetes—Soli De-escalation

1867-LB: A Real-World Study Assessing the Efficacy and Safety of Switching from Basal–Bolus Insulin Therapy to Once-Daily iGlarLixi in People with Type 2 Diabetes—Soli De-escalation

Assessing outcomes of intravenous insulin therapy in non-intensive care patients

ABSTRACT Objectives The aim of this study was to compare outcomes of using intravenous insulin infusion (IVII) therapy for managing hyperglycemia in a non-intensive care unit (ICU) versus an ICU setting. Methods We conducted a retrospective analysis on patients who received IVII for hyperglycemia. The analysis compared variables associated with hypoglycemic events while on IVII, and point-of-care blood glucose control and insulin regimens at discharge. Insulin administration errors occurring on IVII were determined. Results Between November 2020 and August 2022, 881 patients received 1,106 IVIIs (780 in ICU and 326 non-ICU). A cumulative 468 days were spent on IVII in the non-ICU setting and 1564 in the ICU (total 2,032 days). The frequency of hypoglycemia on IVII was higher when provided in the non-ICU vs ICU (1.4% vs 0.7%), p < 0.01). Non-ICU patients had significantly higher average blood glucose during the last 24 h of the hospital stay (185 mg/dL vs 160 mg/dL, non-ICU vs. ICU, Pp < 0.01) and were more likely discharged with basal-bolus insulin therapy (p < 0.01). After adjusting for other variables, the probability of having hypoglycemia (OR 2.35; 95% CI 1.62–3.42; p < 0.001) was higher for the non-ICU cohort. In addition, patients who received IVII in the non-ICU settings had mean glucose levels nearly 26 mg/dL higher (95% CI 19.40–32.9, p < 0.001) at discharge vs. ICU. Seven cases of insulin errors were reported while on IVII in the non-ICU settings, compared to one in the ICU. Conclusions A large number (468) of ICU days were avoided by providing IVII in the non-ICU setting. Of the more than 400 days of IVII therapy provided in the non-ICU, only 7 medication errors occurred. Further studies are needed to optimize IVII strategy for non-ICU patients.

Frequency of hypoglycaemia with basal insulin treatments in adults with type 1 diabetes treated with basal-bolus insulin regimens in treat-to-target trials: A narrative review.

To summarise, in a narrative review, published data on hypoglycaemia occurrence with basal insulin therapy in adults with type 1 diabetes treated with basal-bolus insulin regimens in treat-to-target randomised controlled trials. Data were included from 21 eligible trials, which mainly used self-measured blood glucose or plasma glucose to detect hypoglycaemia. All-day self-measured blood glucose or plasma glucose level 2 (glucose threshold of 3.1 or 3.0 mmol/L) and level 3 (severe, requiring assistance) hypoglycaemic events were reported, respectively, by a range of 69.0%-97.5% and 0%-13.4% adults when receiving basal-bolus insulin therapy, with rates of 10.6-68.1 and 0.0-0.4 events per patient-year of exposure, respectively. Hypoglycaemia rates measured using continuous glucose monitoring (three studies) were numerically, yet consistently, higher than with either other method, except when limiting to symptomatic events. Nocturnal hypoglycaemia rates were generally less than 30% of the equivalent all-day rates. Differences across the studies in design (e.g., titration targets) and participant characteristics hindered comparison of hypoglycaemia rates by insulin formulation. Consequently, few trends were identified by insulin formulation, study methodology or individuals' characteristics, suggesting that further research is required to identify treatment strategies that facilitate development of individualised recommendations to lower hypoglycaemia risk. These findings are useful to understand hypoglycaemia risk with available basal insulin therapies when used in a multiple daily injection regimen, as well as to provide context for the results of ongoing and future clinical trials, including those for two once-weekly basal insulins, insulin icodec and basal insulin Fc.

De-Intensification from Basal-Bolus Insulin Therapy to Liraglutide in Type 2 Diabetes: Predictive Value of Mean Glycaemia during Fasting Test.

Successful conversion from insulin therapy to glucagon-like peptide 1 receptor agonist (GLP-1RA) with basal insulin in well-controlled patients has already been demonstrated. However, the data concerning individuals with poor glycaemic control are scarce. The aim of this work was to assess the success rate of insulin therapy to liraglutide transition in poorly controlled diabetes in a real-world clinical setting and to define predictors of success. We are the first to present the method of a fasting test as a way to identify the patients at higher risk of failure after treatment de-intensification. The retrospective observational study analyzed data of 62 poorly controlled obese diabetic patients on high-dose insulin therapy, who were subjected to a 72 h fasting test during hospitalization and subsequently switched to liraglutide ± basal insulin therapy. During the fasting, all antidiabetic treatment was discontinued. Patients were classified as responders if they remained on GLP-1RA treatment after 12 months. Non-responders restarted the basal-bolus insulin (BBI) regimen. Development of glycated hemoglobin (HbA1c) and body weight in both groups, alongside with parameters associated with the higher risk of return to the BBI regimen, were analyzed. A total of 71% of patients were switched successfully (=responders). Responders had more significant improvement in HbA1c (-6.4 ± 19.7 vs. -3.4 ± 22.9 mmol/mol) and weight loss (-4.6 ± 7.1 vs. -2.5 ± 4.0). Statistically significant difference between groups was found in initial HbA1c (75.6 ± 17.9 vs. 90.5 ± 23.6; p = 0.04), total daily dose of insulin (67.6 ± 36.4 vs. 90.8 ± 32.4; p = 0.02), and mean glycaemia during the fasting test (6.9 ± 1.7 vs. 8.6 ± 2.2 mmol/L; p < 0.01). This study confirms that therapy de-intensification in poorly controlled patients with a BBI regimen is possible. Higher baseline HbA1c, total daily insulin dose, and mean glucose during fasting test are negative predictive factors of successful therapy de-escalation.

Effects of Switching from Degludec to Glargine U300 in Patients with Insulin-Dependent Type 1 Diabetes: A Retrospective Study.

Background and Objectives: Degludec (Deg) and glargine U300 (Gla-300) are insulin analogs with longer and smoother pharmacodynamic action than glargine U100 (Gla-100), a long-acting insulin that has been widely used for many years in type 1 and type 2 diabetes. Both improve glycemic variability (GV) and the frequency of hypoglycemia, unlike Gla-100. However, it is unclear which insulin analog affects GV and hypoglycemia better in patients with insulin-dependent type 1 diabetes. We evaluated the effects of switching from Deg to Gla-300 on the day-to-day GV and the frequency of hypoglycemia in patients with insulin-dependent type 1 diabetes treated with Deg-containing basal-bolus insulin therapy (BBT). Materials and Methods: We conducted a retrospective study on 24 patients with insulin-dependent type 1 diabetes whose treatment was switched from Deg-containing BBT to Gla-300-containing BBT. We evaluated the day-to-day GV measured as the standard deviation of fasting blood glucose levels (SD-FBG) calculated by the self-monitoring of blood glucose records, the frequency of hypoglycemia (total, severe, and nocturnal), and blood glucose levels measured as fasting plasma glucose (FPG) levels and hemoglobin A1c (HbA1c). Results: The characteristics of the patients included in the analysis with high SD-FBG had frequent hypoglycemic events, despite the use of Deg-containing BBT. For this population, SD-FBG and the frequency of nocturnal hypoglycemia decreased after the switch from Deg to Gla-300. Despite the decrease in the frequency of nocturnal hypoglycemia, the FPG and HbA1c did not worsen by the switch. The change in the SD-FBG had a negative correlation with the SD-FBG at baseline and a positive correlation with serum albumin levels. Conclusions: Switching from Deg to Gla-300 improved the SD-FBG and decreased the frequency of nocturnal hypoglycemia in insulin-dependent type 1 diabetes treated with Deg-containing BBT, especially in cases with low serum albumin levels and a high GV.

Complete Agenesis of the Dorsal Pancreas Presenting as Uncontrolled Hyperglycaemia: A Case Report

Agenesis of the Dorsal Pancreas (ADP) is a rare anatomical manifestation of the pancreas, characterised by the total or partial absence of the dorsal pancreatic regions, body, and tail. The anatomy of the pancreas missing the pancreatic tail is considered partial agenesis, while the absence of the body and tail, with the presence of only the pancreatic head, is considered to be complete dorsal agenesis of the pancreas. Here the authors present the case of 20 years old male patient with uncontrolled blood sugars and recent onset of blurred vision. Diagnostic imaging, including Ultrasonography (USG) and Computed Tomography (CT), revealed the pancreatic head, but the body and tail were not seen. Using CT, the patient’s condition was identified as complete ADP. Treatment involved initiating basal bolus insulin therapy, leading to glycaemic control. The patient also underwent cataract surgery for diabetic-related complications. This case underscores the importance of considering congenital pancreatic anomalies in young adults and highlights the utility of advanced imaging techniques in confirming the diagnosis of agenesis of the dorsal pancreas. Early recognition and intervention are crucial for optimising patient outcomes. Further research is needed to enhance understanding of ADP pathophysiology and develop effective management strategies.

Diabete mellito dopo trattamento con ocrelizumab per sclerosi multipla primariamente progressiva

Objectives: immune reconstitution therapies, which include antibody-based cell-depleting therapies targeting CD20+ (ocrelizumab, ofatumumab) or CD52+ (alemtuzumab) leukocytes, are approved for the treatment of multiple sclerosis. Autoimmune thyroid disease is the most common adverse effect of treatment with alemtuzumab, but some cases of autoimmune diabetes have been reported. To date, diabetes mellitus has not been reported after CD20-targeting monoclonal antibodies therapy. Case Report: a 41-year-old man with primary progressive multiple sclerosis was diagnosed with diabetes mellitus six months following the first ocrelizumab infusion. He experienced polyuria and polydipsia, but not other symptoms as visual loss or weight loss. We started a basal-bolus insulin therapy, with progressive and relatively rapid improvement of glycemic control. To note, C-peptide resulted indicative of a preserved beta-cell activity and autoantibodies were negative. To present date, the patient reached an excellent control with metformin. Conclusions: this is the first case of diabetes mellitus reported after ocrelizumab administration. The timing of onset and course are similar to alemtuzumab-induced autoimmune diseases, usually interpreted as an “immune reconstitution syndrome”; however, ocrelizumab cell count depletion appears inferior in duration and cell population affected. This case suggests the need for screening and follow-up of glycemic status in patients treated with ocrelizumab. As a novel therapeutic antibody, further investigation is required to elucidate the correlation between hyperglycemia and ocrelizumab.

A comparison of various deep learning models on blood glucose management of type 1 diabetes: A brief review

Type 1 diabetes has become one of the most common chronic diseases nowadays because patients pancreas cannot produce sufficient insulin, which helps the blood sugar to enter the cells, which will cause them to build up in the bloodstream and leads to complications and dis-eases. Therefore, a basal-bolus insulin therapy that contains daily insulin injections has be-come routine for patients with type 1 diabetes to help regulate the blood sugar level. To better monitor the blood glucose level, digital health monitors are becoming the trending method for type 1 diabetes patients. Meanwhile, all the data generated by the digital monitoring devices made researchers realize that deep learning algorithms could be implanted to help the device better predict a patients blood sugar levels. In this paper, we aim to present a review of testing several state-of-the-art deep-learning models on blood glucose prediction. We have identified a literature search and focused on the deep-learning algorithms for glucose management. After detailed explanations of each model, we employ them on one mutual dataset to identify the direct prediction results of each model and compare the pros and cons of these models accord-ing to the results report. While all these models have the most advanced frameworks, the lack of feature varieties and data availability becomes their limitations. However, followed by the increased focus on the digital health field, these challenges might soon get resolved, which leads to more comprehensive models that could be further deployed in clinical conditions.

The efficacy of switching basal-bolus insulin therapy to basal insulin-supported oral therapy with a glinide and an α-glucosidase inhibitor in patients with type 2 diabetes depends on insulin secretory capacity, but not on blood glucose profiles and insulin dosages prior to the switching.

We aimed to identify patients who would benefit from basal insulin-supported oral therapy (BOT) with a glinide and an α-glucosidase inhibitor (a fixed-dose combination tablet of mitiglinide 10mg and voglibose 0.2mg) in Japanese type 2 diabetic patients. Patients who were hospitalized to improve hyperglycemia received basal-bolus insulin therapy. After the reduction of glucose toxicity, a 75g oral glucose tolerance test and a glucagon test were performed. Thereafter, the basal-bolus insulin therapy was switched to BOT with mitiglinide, followed by further addition of voglibose. Interstitial glucose levels were continuously monitored throughout the study period. Diurnal glucose profile was recorded and analyzed. Patients were divided into two groups according to whether their percentage of time in range (TIR, 70-180mg/dL) under BOT with mitiglinide/voglibose was higher than 70% or not, and the differences in clinical characteristics between the groups were analyzed. Twenty patients were enrolled, and 19 of them completed the study. BOT with mitiglinide/voglibose achieved ≥ 70% of TIR in thirteen patients. The area under the curve of serum C-peptide levels during the oral glucose tolerance test was significantly higher in the patients with ≥ 70% of TIR. The daily insulin dosages and blood glucose profiles were comparable between the two groups. The efficacy of BOT with mitiglinide/voglibose depended on residual insulin secretory abilities. This therapy would be a useful therapeutic option for patients with type 2 diabetes.

Efficacy of switching from basal-bolus insulin therapy to twice-daily insulin degludec/insulin aspart co-formulation plus insulin aspart in patients with poorly controlled type 2 diabetes.

The aim of this study was to evaluate the efficacy of twice-daily (BID) insulin degludec/insulin aspart (IDegAsp) co-formulation + once-daily (OD) bolus insulin aspart (IAsp) injection (IDegAsp BID-Plus) as simplified intensive insulin therapy in patients with poorly controlled type 2 diabetes mellitus (T2DM) with basal-bolus insulin therapy (BBIT). The retrospective study included 155 patients who switched from BBIT to IDegAsp BID-Plus. After the initiation of the treatment, 73 patients continued regular follow-up and insulin doses, number of injections, hemoglobin A1c (HbA1c) levels, and other parameters were recorded from their files at baseline, 24, and 52 weeks. The mean age of the study population was 54.3±10.2 years, the duration of T2DM was 9.7±5.7 years, fasting plasma glucose (FPG) was 252.7±66.7 mg/dl, and HbA1c levels were 10.5±1.5%. Among the included patients, 15 patients received five injections, 51 patients received four injections, and 7 patients received three injections per day. There was a significant decrease in HbA1c (respectively; 10.46±1.54%, 7.97±1.24%, 7.98±1.23%, baseline and 6th-month p<0.001, baseline and 12th-month p<0.001), FPG (respectively; 251.6±66.5 mg/dl, 136.1±34.7 mg/dl, 125.4±67.0 mg/dl, baseline and 6th-month p<0.001, baseline and 12th-month p<0.001) and daily dose of insulin (respectively; 102.9±29.0 Unit, 73.2±18.2 U, 63.7±20.3 Unit, baseline and 6th-month p<0.001, baseline and 12th-month p<0.001) at the end of week 24 and 52. Based on real-world data, this study demonstrated that IDegAsp BID-Plus treatment provides rapid and sustainable blood glucose control with lower insulin doses and fewer injections than previous intensive insulin therapy.

1493-P: Immune-Mediated Diabetes Mellitus—A Rare Complication of Nivolumab Therapy

Background: Immune mediated diabetes mellitus (DM) is a rare complication of immune checkpoint inhibitor (ICI) therapy, with an incidence of less than 1%. We present a case of immune-mediated DM with nivolumab therapy presenting as diabetic ketoacidosis (DKA). Case: A 74-year-old Caucasian male with no history of DM or autoimmune disease was diagnosed with stage III metastatic melanoma and started on treatment with nivolumab, an ICI. He tolerated treatment well and had no evidence of endocrine dysfunction on routine laboratory monitoring. Shortly after completing his 14th cycle of nivolumab therapy, he presented to the emergency department with a one-week history of fatigue, poor appetite, polydipsia, and polyuria. He was found to have DKA with serum blood glucose 446 mg/dL, anion gap 20 mEq/L, serum bicarbonate 14 mEq/L, arterial pH 7.23, and 4+ urine ketones. His hemoglobin A1c was 7.3%, increased from 5.4% one year earlier. He was treated with intravenous insulin then transitioned to basal-bolus subcutaneous insulin therapy, which was continued at discharge. Evaluation in the outpatient setting revealed no measurable GAD65 antibodies or anti-insulin antibodies, but his serum c-peptide was found to be &amp;lt;0.10 ng/mL with corresponding serum blood glucose level 214 mg/dl. This supported a diagnosis of endocrine pancreatic insufficiency, in his case likely immune mediated due to nivolumab therapy. He completed an additional 6 cycles of nivolumab with no further complications. Meanwhile his DM became well-controlled with subcutaneous insulin injections, and he was eventually transitioned to insulin pump therapy. Discussion: ICIs such as nivolumab are known to cause multiple autoimmune complications that can appear at any point during treatment. The underlying mechanisms of beta cell immunotoxicity are incompletely understood, but progression to insulin-dependency appears to be rapid. It is important to recognize new or worsening DM early to avoid life-threatening complications such as DKA. Disclosure S.M.Iqbal: None. C.Houston: None.

ONWARDS and upwards for basal insulin

In this issue of The Lancet, Chantal Mathieu and colleagues present the findings of ONWARDS 4, a phase 3 randomised, open-label, treat-to-target, non-inferiority trial comparing the novel once-weekly insulin icodec (n=291) versus once-daily insulin glargine U100 (n=291) in people with long-standing type 2 diabetes on basal-bolus insulin therapy. 1 Mathieu C Ásbjörnsdóttir B Bajaj HS et al. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial. Lancet. 2023; (published online May 5.)https://doi.org/10.1016/S0140-6736(23)00520-2 Summary Full Text Full Text PDF Google Scholar The trial was conducted in Belgium, India, Italy, Japan, Mexico, the Netherlands, Romania, Russia, and the USA. The participants had a mean duration of type 2 diabetes of 17·1 years (SD 8·4), a mean age at baseline of 59·8 years (SD 10·0), and 304 of the 582 participants were men and 278 were women. The primary outcome in ONWARDS 4 was met, with both icodec and glargine U100 shown to be equally effective at reducing HbA1c from baseline by week 26 (estimated mean change in HbA1c −1·16 percentage points in the icodec group [baseline 8·29%] and −1·18 percentage points in the glargine U100 group [baseline 8·31%]; estimated treatment difference 0·02 percentage points [95% CI −0·11 to 0·15], p<0·0001). Given the age, duration of diabetes, and number of comorbidities of participants, the percentage of time spent with glucose concentrations within the target range of 70–180 mg/dL (3·9–10·0 mmol/L) by week 26 (ie, trial end) was impressive; 66·9% in the icodec group and 66·4% in the glargine group. In addition, the percentage of time spent with glucose concentrations less than 54 mg/dL (<3·0 mmol/L) was low, not differing significantly between the groups (0·7% for the icodec group and 0·6% for the glargine U100 group). Overall, combined level 2 and 3 hypoglycaemia rates were similar between treatment groups, there were no significant differences in weight gain, and no new safety signals emerged. These findings would suggest that once-weekly icodec is a viable therapeutic option for people with type 2 diabetes on a basal-bolus insulin regimen, and, perhaps more importantly, heralds the introduction of once-weekly insulins into clinical practice, an exciting and welcome addition to the insulin family. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trialIn people with long-standing type 2 diabetes on a basal-bolus regimen, once-weekly icodec showed similar improvements in glycaemic control, with fewer basal insulin injections, lower bolus insulin dose, and with no increase in hypoglycaemic rates compared with once-daily glargine U100. Key strengths of this trial include the use of masked continous glucose monitoring; the high trial completion rate; and the inclusion of a large, diverse, and multinational population. Limitations include the relatively short trial duration and the open-label design. Full-Text PDF

Practical guide in using insulin degludec/insulin aspart: A multidisciplinary approach in Malaysia.

Insulin degludec/insulin aspart (IDegAsp) co-formulation provides both basal and mealtime glycaemic control in a single injection. The glucose level-lowering efficacy of IDegAsp is reported to be superior or non-inferior to that of the currently available insulin therapies with a lower rate of overall hypoglycaemia and nocturnal hypoglycaemia. An expert panel from Malaysia aims to provide insights into the utilisation of IDegAsp across a broad range of patients with type 2 diabetes mellitus (i.e. treatment-naive or insulin-naive patients or patients receiving treatment intensification from basal-only regimens, premixed insulin and basal-bolus insulin therapy). IDegAsp can be initiated as once-daily dosing for the main meal with the largest carbohydrate content with weekly dose adjustments based on patient response. A lower starting dose is recommended for patients with cardiac or renal comorbidities. Dose intensification with IDegAsp may warrant splitting into twice-daily dosing. IDegAsp twice-daily dosing does not need to be split at a 50:50 ratio but should be adjusted to match the carbohydrate content of meals. The treatment of patients choosing to fast during Ramadan should be switched to IDegAsp early before Ramadan, as a longer duration of titration leads to better glycated haemoglobin level reductions. The pre-Ramadan breakfast/lunch insulin dose can be reduced by 30%-50% and taken during sahur, while the preRamadan dinner dose can be taken without any change during iftar. Education on the main meal concept is important, as carbohydrates are present in almost all meals. Patients should not have a misconception of consuming more carbohydrates while taking IDegAsp.

Hyporeninemic hypoaldosteronism as a manifestation of autonomic neuropathy in a patient with type 2 diabetes mellitus against the background of coronavirus disease. A clinical case

Coronavirus disease (COVID-19) is often associated with endocrine complications. The article describes a clinical case of the patient with type 2 diabetes mellitus and COVID-19 after which, for the first time, there was a need for basal-bolus insulin therapy, and secondly, a significant arterial hypotension occurred. The mechanism of damage to β-cells of the pancreas in the patient is debatable. After analyzing the features of diabetes course, we found an acute onset of the disease at the age of 44 years with pronounced hyperglycemia and ketosis, which required insulin therapy. Then for a long time there was no need in insulin therapy, and the patient took metformin, having overweight, no antibodies to β-cell antigens. It is also impossible to exclude the effect of SARS-CoV-2 on the secretory function of β-cells of the pancreas. Accordingly, clinical cases are interesting, as their analysis helps to understand not only the mechanism of development and progression of this infection, but also the diagnosis and treatment of its complications. We have described a rare clinical case of the hyporeninemic hypoaldosteronism in the patient with type 2 diabetes mellitus after COVID-19 infection. Afeature of the hyporeninemic hypoaldosteronism course was the absence of electrolyte disorders in the patient, with severe arterial hypotension, suppression of renin and aldosterone. We believe that the hyporeninemic hypoaldosteronism has been associated with the progression of chronic diabetes complications, mainly autonomic neuropathy against the background of COVID-19. To improve the identified disorders, replacement therapy with mineralocorticoids was prescribed. The blood pressure, symptoms of fluid retention and electrolyte levels were monitored when selecting the dose of fludrocortisone. The patient has been under observation for 14 months, the need for fludrocortisone replacement therapy persists to this day. Practicing doctors need to pay attention to the diagnosis of autonomic disorders, which reduce the patients’ quality of life and are an independent risk factor for cardiovascular mortality.

Glucocorticoid-induced hyperglycemia and diabetes: Practical points

Glucocorticoids are widely used in medical practice for their anti-inflammatory action, but lead to hyperglycemia in 30% of cases, due to rapid reduction of insulin secretion and action. Endogenous glucose production is less strongly suppressed by insulin, even small doses such as 7.5mg/day. As they are administered in the morning, glucocorticoids induce hyperglycemic excursion in the afternoon, and at this time screening can be performed by capillary glucose measurement. It is also critical to determine, on medical history and HbA1c assay, whether the patient had prior diabetes, sometimes overlooked, in which case diabetes will not resolve after glucocorticoid discontinuation, and poorly controlled diabetes will often require a basal-bolus insulin therapy in the meantime. This heavy therapy is not suitable for de novo diabetes, as it incurs a risk of nocturnal hypoglycemia, whereas intermediate-acting morning insulin injection provides better cover of hyperglycemia in the afternoon. The British Diabetology Societies recently reported that an even simpler prescription of gliclazide in the morning may be sufficient for some patients. The antidiabetic treatment will have to be monitored, and reduced when glucocorticoid dose is scaled off. Other antidiabetic agents are being tested in trials to develop simple alternatives without risk of hypoglycemia.

Initiation of iGlarLixi Versus Basal-Bolus Insulin in Adults With Type 2 Diabetes Advancing From Basal Insulin Therapy: The SoliComplex Real-World Study.

When type 2 diabetes is suboptimally controlled with basal insulin, prandial insulin injections are commonly added (i.e., a basal-bolus insulin regimen), which can increase treatment burden and hypoglycemia risk. The once-daily injectable iGlarLixi is an alternative treatment. This retrospective analysis of the U.S. Optum Clinformatics database compared outcomes in adults (≥18 years of age) with type 2 diabetes who previously received basal insulin and were newly initiated on iGlarLixi or basal-bolus insulin therapy. Cohorts were propensity score-matched in a 1:1 ratio on baseline characteristics, and imbalances were adjusted in multivariate analyses. Subgroup analyses were performed for people ≥65 years of age and those with a baseline A1C ≥9%. The primary end point was persistence with therapy at 12 months in the overall population. Secondary end points were treatment adherence, health care resource utilization (HCRU), costs, any hypoglycemia, and A1C change at 12 months. Cohorts each comprised 1,070 participants. Treatment persistence at 12 months was statistically significantly higher for iGlarLixi versus basal-bolus insulin therapy (43.7 vs. 22.3%, hazard ratio 0.51, 95% CI 0.46-0.57, adjusted P <0.001). Adherence was numerically higher for iGlarLixi, and hypoglycemia events, HCRU, and costs were numerically lower for iGlarLixi. A1C reduction from baseline was slightly greater for basal-bolus insulin. Results for both subgroups (≥65 years of age and baseline A1C ≥9%) were similar to those of the overall population. In this observational study, initiation of once-daily iGlarLixi versus basal-bolus insulin was associated with higher persistence, lower hypoglycemia, and similar A1C reduction without increasing HCRU or costs regardless of age or A1C. iGlarLixi could be an alternative to basal-bolus insulin, particularly for older adults with type 2 diabetes who require treatment simplification with lower hypoglycemia risk.

Fasting plasma glucose level-based formula for estimating starting daily dose in basal-bolus insulin therapy

There is no standard formula for estimating the starting daily dose (SDD) of basal-bolus insulin therapy (BBT). We aimed to develop a formula for estimating SDD and evaluate its efficacy and safety in patients with type 2 diabetes hospitalized for BBT. In the first study (n = 104), we retrospectively analyzed the relationship between peak daily dose (PDD) during hospitalization and clinical parameters. The PDD was significantly associated with fasting plasma glucose (FPG) (R = 0.449, P < 0.0001) and HbA1c levels (R = 0.384, P < 0.0001) but not body weight, body mass index, body surface area, or serum C-peptide levels. Based on the results, we developed a formula for estimating SDD using FPG levels: SDD (U/day) = 0.08 × FPG (mg/dL). In the second study (n = 405), we assessed efficacy and safety of the formula by evaluating the M-value from the daily glucose profile and assessing the frequency of hypoglycemia (blood glucose level < 70 mg/dL). When BBT was initiated using the FPG level-based formula, the M-values decreased from 61.0 ± 52.8 to 12.8 ± 10.8 (P < 0.0001), and hypoglycemia was observed in only 3/405 cases (0.74%) under the SDD. The FPG level-based formula is useful for estimating SDD in BBT and is safe for clinical use.