Basal-bolus Approach Research Articles

“A simplified Therapeutic Approach in Patients with Type 2 Diabetes Mellitus Through the Use of the Fixed-Ratio Combination of Insulin Glargine Plus lixisenatide (iglarlixi): An Account of Our Experience in Frail Elderly Patients”

Background and Aims Approximately 50% of patients with type 2 diabetes mellitus do not reach glycemic targets and need treatment intensification or simplification. The aim of the study was to reduce the use of basal bolus approach among frail elderly patients to avoid hypoglycemia or to intensify treatment in case of hyperglycemia. The application of fixed-ratio combination of insulin glargine/ lixisenatide (iGlarLixi) promotes the mechanism of action of both drugs on hyperglycaemia while minimizing adverse effects. Materials/Patients and Methods We enrolled 70 patients (aged>65) from July to December 2023 referred to our outpatients visit or admitted to Endocrine Diseases department. 60% of patients presented basal bolus therapy and with at least 3 episodes of recent hypoglycaemia, while 40% of patients severe hyperglycaemia, requiring therapy intensification. Results 45% of patients treated with iGlarLixi achieved an improvement in glycated hemoglobin already in the first 3 months of therapy with an average reduction of approximately 1 unit. Additionally, 30% of patients who transitioned from basal bolus therapy to iGlarLixi achieved an average weight loss of 4 kg. Discussion In our experience in frail elderly patients the use of iGlarLixi has revealed improvement in both fasting and postprandial blood glucose, reducing the risk of fasting hypoglycaemia. Moreover, it proved to be an effective treatment for enhancing glycated haemoglobin levels and reducing body weight.

“A simplified Therapeutic Approach in Patients with Type 2 Diabetes Mellitus Through the Use of the Fixed-Ratio Combination of Insulin Glargine Plus lixisenatide (iglarlixi): An Account of Our Experience in Frail Elderly Patients”

Background and Aims Approximately 50% of patients with type 2 diabetes mellitus do not reach glycemic targets and need treatment intensification or simplification. The aim of the study was to reduce the use of basal bolus approach among frail elderly patients to avoid hypoglycemia or to intensify treatment in case of hyperglycemia. The application of fixed-ratio combination of insulin glargine/ lixisenatide (iGlarLixi) promotes the mechanism of action of both drugs on hyperglycaemia while minimizing adverse effects. Materials/Patients and Methods We enrolled 70 patients (aged>65) from July to December 2023 referred to our outpatients visit or admitted to Endocrine Diseases department. 60% of patients presented basal bolus therapy and with at least 3 episodes of recent hypoglycaemia, while 40% of patients severe hyperglycaemia, requiring therapy intensification. Results 45% of patients treated with iGlarLixi achieved an improvement in glycated hemoglobin already in the first 3 months of therapy with an average reduction of approximately 1 unit. Additionally, 30% of patients who transitioned from basal bolus therapy to iGlarLixi achieved an average weight loss of 4 kg. Discussion In our experience in frail elderly patients the use of iGlarLixi has revealed improvement in both fasting and postprandial blood glucose, reducing the risk of fasting hypoglycaemia. Moreover, it proved to be an effective treatment for enhancing glycated haemoglobin levels and reducing body weight.

Cardiovascular Safety of Antidiabetic Drugs in the Hospital Setting.

Patients with diabetes and/or stress hyperglycemia requires good glycemic control in the hospital setting, often requiring the use of glucose-lowering therapy. Standard-of-care dictates that non-insulin therapy be discontinued, with insulin therapy initiated using a basal-bolus approach. However, insulin is associated with a high risk for hypoglycemia and medical errors. Alternatives to insulin are needed in the inpatient setting, but the cardiovascular (CV) safety of non-insulin therapy is a concern. Most studies of antidiabetic drugs have been performed in the outpatient setting, and except for insulin therapy, trials in the inpatient setting have been insufficient to establish CV safety. Randomized controlled trials support the safety of insulin with more moderate glycemic control in the hospital, when hypoglycemia is minimized. Two recent multicenter randomized controlled clinical trials support the safety of sitagliptin, a dipeptidylpeptidase-4 inhibitor (DPP4i), in hospitalized patients, although the sample sizes were likely too small to detect CV events. Small trials suggest a possible CV benefit of glucagon-like peptide-1 receptor agonist therapy. A paucity of evidence and presence of side effects and cautions with insulin secretagogues, sodium glucose-co-transporter-2 inhibitors, and metformin preclude their routine use in the hospital setting. Available evidence is inadequate to evaluate the CV safety of most antidiabetic drug classes in the hospital setting. However, preliminary data from randomized clinical trials suggest the potential safety of the DPP4i sitagliptin.

Annals for Educators - 2 May 2017

Annals for Educators - 2 May 2017

Real world outcomes of adding rapid-acting insulin versus switching to analog premix insulin among US patients with type 2 diabetes treated with insulin glargine

IntroductionPatients with type 2 diabetes mellitus (T2DM) often require intensification of basal insulin therapy. This retrospective, observational study compared real-world outcomes in US patients with T2DM treated with insulin glargine who added a rapid-acting insulin (RAI) (basal–bolus approach) with those who switched to premixed insulin (PMX).MethodsThe national US IMPACT® database was used to identify data from adult patients (≥18 years of age) with T2DM who added bolus RAI to insulin glargine (GLA + RAI) or who switched from GLA to PMX between 2001 and 2009. A stringent 1:1 propensity score-matching method was used to address the selection bias by matching GLA + RAI patients and PMX patients. Clinical and economic outcomes were determined for 1 year after the initial pharmacy claim for RAI or for PMX. Outcomes included treatment persistence and adherence, average insulin doses, glycated hemoglobin (A1C) levels, the prevalence and incidence of hypoglycemia, and health care costs/utilization. Analysis was carried out using an intent-to-treat approach.ResultsThe study included data from 746 propensity-matched patients (n = 373 in each cohort). Treatment persistence and adherence were higher in the GLA + RAI cohort. There was no significant difference in A1C reduction from baseline and the number of patients achieving target A1C levels of <7% in each cohort. The incidence of hypoglycemic events was also similar in both groups. However, during follow-up, many patients (48.8%) who initially switched from insulin glargine to PMX crossed back over to use GLA and/or RAI as part of their regimen. Health care costs and utilization levels were not significantly different.ConclusionClinical and economic outcomes were similar in T2DM patients who added RAI to GLA and in those who switched to PMX, but a basal–bolus strategy appears to be associated with better treatment persistence and adherence.

Comparison of stepwise addition of prandial insulin to a basal-bolus regimen when basal insulin is insufficient for glycaemic control in type 2 diabetes: Results of the OSIRIS study

The metabolic efficacy of adding prandial insulin in a stepwise manner to a straightforward basal-bolus regimen was compared in patients with type 2 diabetes mellitus (T2DM), suboptimally controlled by oral antidiabetic drugs (OADs) and once-daily basal insulin. In this international randomized, parallel-group, non-inferiority study, 811 patients with poorly controlled type 2 diabetes using basal insulin were switched to insulin glargine (GLAR) for 6 months while continuing OADs. Patients with HbA(1c) > 7% and FPG < 120 mg/dL (n=476) were then randomized to either group 1, GLAR+metformin (MET)+3×insulin glulisine (GLU), group 2, GLAR+MET+1-3×GLU, or group 3, GLAR+MET+insulin secretagogue (IS)+1-3×GLU, for 12 months. Objectives were to show the non-inferiority of efficacy of group 2 vs group 1 and vs group 3. Non-inferiority of group 2 vs group 1 was concluded if the upper limit of the 95% confidence interval (CI) for the HbA(1c) difference was ≤ to 0.4%. The adjusted HbA(1c) difference of group 2 vs 1 for the per-protocol population crossed the non-inferiority margin (0.228, 95% CI: -0.018-0.473). There was significantly less weight gain in group 2 compared with group 1, but adverse events were otherwise similar between the two groups. In patients with HbA(1c) < 8% at baseline, non-inferiority was achieved in group 2 vs group 1. Although non-inferiority was not achieved, stepwise intensification of GLU added to GLAR showed efficacy close to that of the basal-bolus approach and with significantly less weight gain.

Ten years of experience with biphasic insulin aspart 30: from drug development to the latest clinical findings.

Biphasic insulin aspart 30 (BIAsp 30) includes 30% soluble rapid-acting insulin aspart (IAsp) along with an intermediate-acting 70% protaminated IAsp that provides coverage of prandial and basal insulin in a single injection. As BIAsp 30 has been available internationally for 10 years, this review provides a comprehensive overview of the discovery of BIAsp 30, its pharmacokinetic and pharmacodynamic profile, safety and efficacy outcomes from the clinical trial programme, ‘real-life’ clinical insights provided by observational study data, and cost effectiveness and quality-of-life information. These studies have demonstrated that BIAsp 30 once or twice daily is an appropriate option for insulin initiation. BIAsp 30 also provides a switch option in patients on biphasic human insulin (BHI). Switching from BHI to BIAsp 30 is associated with improved postprandial glucose (PPG) and reduced nocturnal and major hypoglycaemia, although daytime hypoglycaemia is higher with BIAsp 30. Intensification of BIAsp 30 can be achieved by increasing the number of daily doses up to three times daily with meals. Therefore, BIAsp 30 provides an intensification option for individuals who are not achieving control with basal insulin and would prefer the simplicity of a single biphasic insulin instead of progressing to a basal-bolus approach. BIAsp 30 has a simple dose-titration algorithm, which enables patients to effectively self-titrate their insulin dose. Cost-effectiveness analyses have demonstrated that BIAsp 30 is cost effective or dominant compared with BHI 30 or insulin glargine in a number of healthcare settings. In conclusion, BIAsp 30 offers a simple and flexible option for insulin initiation and intensification that provides coverage of both fasting and prandial glucose.

How Basal Insulin Analogs Have Changed Diabetes Care

How Basal Insulin Analogs Have Changed Diabetes Care

A Stepwise Approach to Insulin Therapy in Patients with Type 2 Diabetes Mellitus and Basal Insulin Treatment Failure

To determine whether 1 or 2 preprandial injections before the meals of greatest glycemic impact can be as effective as 3 preprandial injections in patients with type 2 diabetes mellitus and basal insulin treatment failure. This was an open-label, parallel-group, 1:1:1 randomized study of adults with type 2 diabetes mellitus on oral antidiabetic drugs with glycated hemoglobin (A1C) levels of 8.0% or greater. After a 14-week run-in with insulin glargine, patients with an A1C level greater than 7.0% were randomly assigned to 1, 2, or 3 time(s) daily insulin glulisine for 24 weeks. Changes in A1C from randomization to study end; percentage of patients achieving an A1C level less than 7.0%; changes in A1C, fasting glucose concentrations, and weight at individual study points; and safety (adverse events and hypoglycemia) were assessed throughout the study. Three hundred forty-three of 631 patients (54%) completing the run-in phase with insulin glargine were randomly assigned to treatment arms. During the randomization phase, A1C reductions with insulin glulisine once or twice daily were noninferior to insulin glulisine 3 times daily (confidence intervals: -0.39 to 0.36 and -0.30 to 0.43; P>.5 for both). However, more patients met the target A1C with 3 preprandial injections (46 [46%]) than with 2 injections (34 [33%]) or 1 injection (30 [30%]). Severe hypoglycemia occurred in twice as many patients receiving 3 preprandial injections (16%) compared with those receiving 2 injections (8%) and 1 injection (7%), but these differences did not reach significance. This study provides evidence that initiation of prandial insulin in a simplified stepwise approach is an effective alternative to the current routine 3 preprandial injection basal-bolus approach.

Insulinización intensiva de choque en el debut de la diabetes mellitus tipo 2, seguida de tratamiento oral posterior

A 32-year-old male patient, smoker and with a sedentary lifestyle, was referred to our Diabetes-Day-Care Center from Primary Care due to a random blood sugar level greater than 300mg/dl for evaluation and subsequent follow-up. An onset of type 2 diabetes mellitus, grade 1 obesity, dyslipidemia, arterial hypertension and metabolic syndrome were diagnosed. In addition to nutritional conselling, advice regarding tobacco cessation and certain lifestyle-related aspects, intensive insulinization was initiated based on a basal-bolus approach, along with antihypertensive treatment and primary prevention of cardiovascular events. The subsequent, gradual introduction of oral antidiabetic drugs (metformin and repaglinide) allowed us to sustain good glycemic results and withdraw insulin treatment. Noteworthy in this case is the use, in accordance with in recent years published study results, of an intensive insulin therapy at the onset of type 2 diabetes mellitus aiming at improving beta-cell function and possibly achieving prolonged maintenance of their function.

Reducing Hyperglycemia Hospitalwide: The Basal-Bolus Concept

Hyperglycemia has been identified as potent and independent risk factor for adverse outcomes for patients. An initiative was undertaken to reduce hyperglycemia hospitalwide in adults. In a multistep process, insulin protocols were implemented hospitalwide via an electronic provider order entry system. Education regarding basal bolus insulin delivery preceded implementation. Protocols were modified in an ongoing manner on the basis of clinical staff feedback and blood glucose monitoring. Key practice changes included intravenous insulin for initial management in ICU patients, insulin replacement based on the basal bolus approach, elimination of sliding-scale insulin, standardization of blood glucose monitoring before meals, adjustment of prandial dose insulin based on food consumed, administration of prandial dose after the meal, evening snacks ordered based on insulin type, and a glycosolated hemoglobin (A1C) determination for patients with admission glucose > 180 mg/dL. Median inpatient glucose levels in patients with diabetes were assessed using statistical process control methodology. Between January 2004 and September 2007, median glucose for all inpatients with diabetes decreased 15% from 159 mg/dL to < 135 mg/dL. The percentage of inpatients with diabetes who experienced a day with a glucose measurement above 180 mg/dl decreased from 66% to 53%. Frequency of hypoglycemia (< 60 mg/dL) did not change following protocol implementation. Major improvements in hospitalwide blood glucose control are feasible and safe, employing standard protocols based on the basal-bolus concept. Improvement was sustained during a four-year period with ongoing institutional support, multidisciplinary education, collaboration between clinical services, and monitoring of clinical outcomes on a quarterly basis.

Insulin glulisine: aspects of basal/bolus therapy for optimized treatment of diabetes mellitus

Background/objective: The prevalence of diabetes mellitus continues to increase throughout the world with an expected doubling of documented cases between 2006 and 2030, diabetes deaths are expected to increase by more than 50% from 2006 to 2015. Therapeutic interventions should be based on scientific evidence, including earlier insulin initiation and use of a basal-bolus approach that better mimics normal physiology. Methods: This review focuses on insulin glulisine in the basal-bolus approach. It details pharmacological data, clinical efficacy, safety and tolerability, and potential effects on current treatment regimens. Results/conclusion: Insulin glulisine offers a more rapid onset of action and shorter duration of action compared with regular human insulin. These characteristics result in an action profile that closely mimics the normal postmeal endogenous insulin response, thus fulfilling the prandial insulin requirement and making the basal-bolus treatment approach clinically achieveable.

Recent advances in insulin treatment of children

Since the findings of the Diabetes Control and Complications Trial became public in 1993, intensive insulin therapy has been recommended for all children. However, successful implementation remains a challenge because of developmental, physiological and cultural, as well as practical issues specific to the pediatric population. This article reviews the different insulin regimens that are currently available, from the short- and intermediate-acting insulins to the newer insulin analogs, focusing on insulin therapies that attempt to provide a more physiologic basal-bolus approach to treatment. More and more children are on multiple daily injection regimens or using continuous subcutaneous insulin infusion to achieve better metabolic control. The achievement of optimal glycemic control in children is complicated by their variability in eating habits and activity levels and perhaps more importantly by the risk of hypoglycemia. The hope is that new technologies including continuous subcutaneous glucose monitoring and perhaps a closed-loop system in the near future will help us achieve more optimal glycemic targets in children without increased side effects. In addition, continuous glucose monitoring may teach us better ways to use insulin in children who do not have the technology available to them.

Insulin Management of Diabetic Patients on General Medical and Surgical Floors

To review the standardized subcutaneous insulin protocols for diabetic patients on general medical and surgical floors at the University of Vermont. Insulin protocols were developed for inpatients eating regular meals, and those receiving continuous tube feedings or total parental nutrition. The recommended starting subcutaneous insulin protocol for patients receiving meals is a basal-bolus approach using 0.5 U/kg basal insulin (glargine once daily, or neutral protamine Hagedorn [NPH] twice daily) and 0.1 U/kg rapid analog at each meal (lispro, aspart, or glulisine) for the average patient. The dose of basal is lowered by 0.2 U/kg for medical conditions with a high sensitivity to insulin or that have an added risk for hypoglycemia (renal or hepatic impairment, thin or normal weight, elderly, frail, hypothyroidism, adrenal insuffi ciency, etc.). Alternatively, an extra 0.2 U/kg basal is given for states of presumed high insulin resistance such as marked obesity with metabolic syndrome, open wounds, infections, etc. In turn, patients receiving continuous tube feedings receive the same 24-hour insulin doses (0.6-1.0 U/kg) in divided doses of premixed 70/30 (NPH/regular) insulin every 8 hours. This program allows lowering or eliminating 1 of the doses for the increasingly common tube-feeding programs in rehabilitation centers or patients' homes that entail discontinuation of tube feeding for 6 to 8 hours. A variation on this approach is used with total parenteral nutrition (TPN), with a portion of the insulin placed in the TPN bag and the remainder given as "q 8 hour 70/30" insulin. Starting insulin doses for all of the programs are adjusted daily to attain inpatient blood glucose goals of <110 mg/dL fasting and 110 to 180 mg/dL throughout the day. Standardized protocols have been developed and implemented at the University of Vermont for patients receiving regular meals and continuous tube feedings or TPN.

A Review of Types 1 and 2 Diabetes Mellitus and Their Treatment with Insulin

Diabetes is a chronic disease characterized by hyperglycemia, and the prevalence of type 2 diabetes is growing to epidemic proportions in certain populations. Type 1 diabetes is primarily the result of autoimmune destruction of beta cells. Type 2 diabetes is found in those with resistance to the action of insulin, usually as a result of obesity, and deficient insulin secretion. Insulin use not only prevents hyperglycemic emergencies, but also is the best safeguard to prevent the long-term complications of diabetes by correcting fasting and postprandial hyperglycemia. Intensive glycemic control can lead to a substantial decrease in the development of microvascular changes found in patients with diabetes. Human insulin analogs, insulins manufactured by recombinant technology which contain substituted or rearranged amino acids, allow more physiological patterns of insulin replacement, termed the basal-bolus approach. Serious hypoglycemia is the biggest obstacle for patients with diabetes treated with intensive insulin programs. Insulin is now available in prefilled pens or can be delivered by a programmable pump to allow greater flexibility in use and to improve glycemic control. Whereas hyperglycemic emergencies are usually treated with intravenous fluids and an intravenous continuous insulin infusion, patients who are less critically ill can be treated with fluid and subcutaneous insulin analogs.

Eliminating Inpatient Sliding-Scale Insulin: A Reeducation Project With Medical House Staff

The study by Baldwin et al. (1) had the laudable intention of training house staff in moving away from inpatient sliding-scale insulin in favor of a basal-bolus approach or active titration of oral agents. However, some key points in their report remain unexplained. The authors state that in insulin-treated patients, the premeal short-acting insulin (usually regular) in combination with a basal insulin (usually NPH) was used. However, no details are given as to how the NPH was titrated and what parameters, if any, were used for adjustment. Even more notable …

Basal Insulin Therapy in Type 2 Diabetes

Patients with type 2 diabetes mellitus are usually treated initially with oral antidiabetic agents, but as the disease progresses, most patients eventually require insulin to maintain glucose control. Optimal insulin therapy should mimic the normal physiologic secretion of insulin and minimize the risk of hypoglycemia. This article discusses the role of insulin therapy in patients with type 2 diabetes, emphasizing long-acting insulin agents designed to approximate physiologic basal insulin secretion and provide control over fasting plasma glucose. Clinical trials of recently developed long-acting insulins are reviewed herein, with emphasis on studies that combined basal insulin with oral agents or with short-acting insulins in a basal-bolus approach. The normal physiologic pattern of insulin secretion by pancreatic beta cells consists of a sustained basal insulin level throughout the day, superimposed after meals by relatively large bursts of insulin that slowly decay over 2 to 3 hours (bolus insulin). Basal support with long-acting insulin is a key component of basal-bolus therapy for patients with diabetes who require insulin with or without the addition of oral agents. Newer long-acting agents such as insulin glargine provide a steadier and more reliable level of basal insulin coverage and may have significant advantages over traditional long-acting insulins as part of a basal-bolus treatment strategy.