Safety Of Insulin Therapy Research Articles

7363 Comparing the Effectiveness of Various Insulin in Insulin Naive Type 2 Diabetes Mellitus Patients: A Study from Central India

Abstract Disclosure: K. Dash: None. S. Verma: None. U. Ayyagari: None. N. Kumari: None. A. Gwal: None. Introduction: Insulin is the cornerstone of treatment of type 2 diabetes mellitus (T2DM) and is the most efficacious treatment option. The evaluation of efficacy and safety of insulin therapy in real world setting is desirable as numerous options are currently available. This study aimed to compare the efficacy and safety of four different insulins in patients with T2DM. Methods: We conducted a retrospective observational study at our tertiary care hospital using medical records of patients with glycated hemoglobin (HbA1c) >8.5% who were not controlled on oral antidiabetic (OAD) medication and received add-on insulin treatment (Glargine U300, Lispro Biphasic 25/75, Glargine U100, IdegAsp). Glycemic control and incidence of hypoglycemia were analyzed from baseline to 6 months. Results: 101 patients were included. Mean age 56.4 years. 61.4% men. Mean duration of T2DM 13.3 years. 23 (22.8%), 27 (26.7%), 27 (26.7%), and 24 (23.8%) patients received Glargine U300, Lispro Biphasic 25/75, Glargine U-100, IdegAsp insulin respectively. At baseline, the mean (SD) HbA1c were 11.93% (1.85), 10.61% (1.55), 10.65% (1.59), and 10.58% (1.89) in patients receiving Glargine U300, Lispro Biphasic 25/75, Glargine U100, and IdegAsp, respectively. HbA1c, fasting plasma glucose (FPG) & post-prandial plasma glucose (PPG) improved significantly from baseline to 6 months across all four treatment groups (p<0.001). Glargine U300 showed a significantly greater mean reduction in HbA1c by 4.57% compared to Lispro Biphasic 25/75 (3.39%; p=0.032), Glargine U100 (2.88%; p=0.004), and IdegAsp (2.38%; p<0.001). The mean reduction in FPG, PPG, total cholesterol and triglycerides were comparable across all four treatment groups. The mean insulin doses (SD) were 15.48 (5.65) U, 23.83 (9.49) U, 20.44 (8.76) U, and 34.17 (14.57) U at baseline and 18.89 (5.39) U, 35.52 (10.37) U, 26.07 (8.92) U, and 43.58 (15.76) at 6 months, respectively. The doses of all insulins were titrated to fasting, post-meal, or pre-dinner SMBG readings as appropriate. There were no significant changes observed in the mean body weight and insulin dose in all four subgroups. The incidence of hypoglycemia (<70 mg/dL and <54 mg/dL) was numerically lower in Glargine U300 (3 and 1) group, than in Lispro Biphasic 25/75 (8 and 5), Glargine U100 (3 and 2), and IdegAsp (7 and 3) groups. As expected, biphasic insulin had a higher numerical incidence of hypoglycemia. Conclusion: All insulins demonstrated significant improvements in glycemic parameters over the study period. However, Glargine U300 demonstrated a significantly higher reduction in HbA1c with minimal hypoglycemia events compared to other insulins and can be considered in OAD uncontrolled patients. Our results should be interpreted with caution as the study was retrospective and had a small sample size. Presentation: 6/3/2024

S50 Insulin Therapy vs Plasmapheresis in Patients With Hypertriglyceridemia-Associated Pancreatitis: A Systematic Review and Meta-Analysis

Introduction: Insulin therapy (IT) and plasmapheresis are used to treat hypertriglyceridemia-associated pancreatitis (HTAP). However, the optimal treatment modality for lowering the triglyceride level in patients with HTAP remains unclear. Therefore, we evaluated the efficacy and safety of IT and plasmapheresis in managing HTAP. Methods: We performed a comprehensive literature search using PubMed, Embase, and Web of Science databases through May 30, 2022, for all studies that compared IT vs. plasmapheresis in patients with HTAP. The primary outcomes were effectiveness (reduction in triglycerides within 24-hours of admission) and clinical outcomes, including hospital length-of-stay (LOS), mortality, acute renal failure (ARF), hypotension, and need for invasive mechanical ventilation (IMV). The secondary outcome was the overall treatment-related adverse events (AEs). Random-effects meta-analysis was conducted, and risk ratio (RR) and mean difference (MD) or standardized mean difference (SMD) for proportional and continuous variables were computed, respectively. For each outcome, forest plot, 95% confidence interval (CI), P-value (< 0.05 considered statistically significant), and I2 statistic ( > 50% considered as significant heterogeneity) were generated. Results: Six studies (1 randomized controlled trial [RCT] and 5 cohort studies) with 302 patients with HTAP (167 on IT vs. 135 on plasmapheresis) were included. Plasmapheresis was more effective than IT in reduction of triglycerides within 24-hours (SMD -0.57; 95% CI -1.02, -0.13; P=0.01, I2=56.8%, Figure 1A). However, LOS (MD -1.96; 95% CI -4.45, 0.54; P=0.12; I2=0%, Figure 1B), mortality (RR 0.68, 95% CI 0.28-1.64, P=0.39, I2=0%, Figure 1C), ARF (RR 0.44, 95% CI 0.06-3.05, P=0.41, I2=84%), hypotension (RR 0.63, 95% CI 0.16-2.52, P=0.51, I2=79%), and need for IMV (RR 0.52, 95% CI 0.12-12.35, P=0.40, I2=80%) were similar between two groups. The treatment-related AEs were significantly lower in IT than plasmapheresis (RR 0.14, 95% CI 0.04-0.51, P=0.003, I2=0%, Figure 1D). Conclusion: Our meta-analysis demonstrated that despite the greater reduction of triglycerides with plasmapheresis compared to insulin therapy, the clinical outcomes, including LOS, mortality, ARF, hypotension, and need for IMV, were comparable with lower treatment-related adverse events with insulin therapy. Future large-scale RCTs are necessary to validate our findings.Figure 1.: Forest plots comparing between insulin therapy and plasmapheresis regarding: (A) the reduction of triglyceride within 24 hours, (B) length of hospital stay, (C) mortality, and (D) treatment-related adverse events.

Race/ethnicity and challenges for optimal insulin therapy

AimsWe aimed to review insulin dosing recommendations, insulin regulation and its determinants, glycaemic response to carbohydrates, and the efficacy and safety of insulin therapy in different races/ethnicities. MethodsWe searched for articles in PubMed and Google Scholar databases up to 31 March 2021, with the following keywords: “ethnicity”, “diabetes”, “insulin”, “history of insulin”, “insulin therapy”, “food/rice”, “carbohydrate intake”, “insulin resistance”, “BMI”, “insulin dosing”, “insulin sensitivity”, “insulin response”, “glycaemic index”, “glycaemic response”, “efficacy and safety”, with interposition of the Boolean operator “AND”.In addition, we reviewed the reference lists of the articles found. ResultsThe differential effect of race/ethnicity has not yet been considered in current insulin therapy guidelines. Nevertheless, body size and composition, body mass index, fat distribution, diet, storage, and energy expenditure vary significantly across populations. Further, insulin sensitivity, insulin response, and glycaemicresponse to carbohydrates differ by ethnicity. These disparities may lead to different insulin requirements, adversely impacting the efficacy and safety of insulin therapy among ethnic groups. ConclusionsRace/ethnicity affects glucose metabolism and insulin regulation.Until now, international guidelines addressing racial/ethnic-specific clinical recommendations are limited. Comprehensive updated insulin therapy guidelines by ethnicity are urgently needed.

Smarter Modeling to Enable a Smarter Insulin.

> I dream things that never were, and I say “Why not?” > > —George Bernard Shaw Pancreatic β-cells secrete insulin to maintain physiological health. While the glucose level is the principle driver of insulin secretion, β-cells also respond to other regulatory inputs including circulating metabolites (most notably amino acids), regulatory hormones, gut peptides, and neurotransmitters. Insulin secretion increases when glucose levels are high, thereby increasing total body glucose utilization and suppressing endogenous glucose production. Of critical importance, insulin secretion is suppressed when glucose levels are low, which protects against life-threatening hypoglycemia. There have been remarkable advances to enhance efficacy and safety of insulin therapy since the discovery of insulin 100 years ago. Insulin pharmacokinetics has been optimized through both formulation and modification of the peptide itself. Sophisticated mechanical devices can provide continuous insulin delivery and continuous glucose monitoring. Pancreatic islets can be transplanted, and bihormonal pumps more closely mimic normal physiology. Despite technological advances, most insulin-dependent patients do not achieve physiological glucose control. The risk of severe hypoglycemia is particularly troublesome because it limits the ability to safely achieve optimal glycemic control, which in turn makes it harder to protect against the long-term risk of microvascular complications (1,2). To underscore this point, half of the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) cohort experienced severe hypoglycemia (∼40 episodes per 100 patient-years) (3). Furthermore, self-reported severe hypoglycemia is associated with 3.4-fold increased risk of death during a 5-year follow-up period (4). The pursuit of a glucose-responsive insulin (GRI) therapy is an ambitious technical objective. In type 2 diabetes, incretin therapy enhances insulin secretion when glucose levels are high but does not cause hypoglycemia because it does not promote insulin secretion when glucose levels are low. Similarly, GRI technology aims to mimic the ability of β-cells …

Insulin therapy for adult patients with type 2 diabetes mellitus: a position statement of the Korean Diabetes Association, 2017.

The Korean Diabetes Association (KDA) has regularly updated its Clinical Practice Guidelines. In 2017, the KDA published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). Growing evidence from new multinational clinical trials using novel and traditional insulin analogues has also been accumulated. Following global trends, many results of clinical trials, especially concerning the clinical efficacy and safety of insulin therapy, have been published about Korean patients with T2DM. After a systematic search of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the initiation, choice, and intensification of insulin and created an insulin treatment algorithm for the first time to guide physicians caring for adult Korean patients with T2DM.

Insulin Therapy for Adult Patients with Type 2 Diabetes Mellitus: A Position Statement of the Korean Diabetes Association, 2017.

The Korean Diabetes Association (KDA) has regularly updated its Clinical Practice Guidelines. In 2017, the KDA published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). Growing evidence from new multinational clinical trials using novel and traditional insulin analogues has also been accumulated. Following global trends, many results of clinical trials, especially concerning the clinical efficacy and safety of insulin therapy, have been published about Korean patients with T2DM. After a systematic search of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the initiation, choice, and intensification of insulin and created an insulin treatment algorithm for the first time to guide physicians caring for adult Korean patients with T2DM.

Insulin therapy in people with type 2 diabetes: opportunities and challenges?

Given the continued interest in defining the optimal management of individuals with type 2 diabetes, the Editor of Diabetes Care convened a working party of diabetes specialists to examine this topic in the context of insulin therapy. This was prompted by recent new evidence on the use of insulin in such people. The group was aware of evidence that the benefits of insulin therapy are still usually offered late, and thus the aim of the discussion was how to define the optimal timing and basis for decisions regarding insulin and to apply these concepts in practice. It was noted that recent evidence had built upon that of the previous decades, together confirming the benefits and safety of insulin therapy, albeit with concerns about the potential for hypoglycemia and gain in body weight. Insulin offers a unique ability to control hyperglycemia, being used from the time of diagnosis in some circumstances, when metabolic control is disturbed by medical illness, procedures, or therapy, as well as in the longer term in ambulatory care. For those previously starting insulin, various other forms of therapy can be added later, which offer complementary effects appropriate to individual needs. Here we review current evidence and circumstances in which insulin can be used, consider individualized choices of alternatives and combination regimens, and offer some guidance on personalized targets and tactics for glycemic control in type 2 diabetes.

Improved glycemic control in pancreatic diabetes through intensive conservative insulin therapy

ObjectiveThe aim of this study was to evaluate the effectivity and safety of insulin therapy in patients with DM secondary to underlying chronic pancreatitis with initially inappropriate glycemic control. MethodsPancreatic DM patients treated with oral antidiabetics (OAD) or pre-mixed insulin (PMI) with HbA1c ≥7.0% were recruited. Intensive conservative insulin treatment (ICT) (Group A, n = 16) or PMI (Group B, n = 8) was introduced instead of OAD, or the initial PMI therapy was switched to ICT (Group C, n = 10). The changes in HbA1c, fasting plasma glucose, body weight and hypoglycemic events from baseline to 2 years were followed. ResultsThe patients in Group A and B had been treated with oral antidiabetics for 55 ± 68 months before switching to insulin therapy. The level of HbA1c had worsened from 8.3 ± 1.5% to 9.8 ± 1.7% during this period. The ICT had reduced HbA1c significantly from 9.7 ± 1.8% to 7.6 ± 1.4% after 12 weeks, in Group A, and five patients had HbA1c<7.0%. The introduction of PMI in Group B reduced HbA1c from 10.0 ± 1.4% to 9.0 ± 0.6% by 12 weeks. None of the patients had HbA1c<7.0%. By 12 weeks, the introduction of ICT in Group C had reduced the level of HbA1c from 8.8 ± 1.7% to 7.7 ± 1.2%. Two patients reached HbA1c<7.0%. There were two severe hypoglycemic episodes during the 2 years, one–one case in Group A and B. ConclusionsOral medication becomes insufficient early in pancreatic DM. Long-term improvement of glycemic control can be achieved through intensified insulin therapy and in selected cases through PMI with a low risk of hypoglycemia.

Increased insulin dose requirement of long-acting insulin analogues in obese patients with type 2 diabetes

To the Editor: Obesity, type 2 diabetes, insulin resistance and hyperinsulinaemia are associated with an increased risk of some types of cancer, and recent epidemiological data have refuelled discussions on the safety of insulin therapy [1]. The data published in the last issue of Diabetologia raise concern but do not provide evidence that any of the specific insulin preparations cause harm; there are too many confounders for which adjustment remains imperfect. Whether the potential risks of insulin preparations with increased affinity to type 1 IGF receptors are acceptable remains a matter of debate. We wish to point out that (apart from the intrinsic properties of an insulin preparation) higher levels of continuous insulin exposure resulting from the choice of insulin preparation should also be considered as a potential drawback. A similar (unit-based) glucose-lowering efficacy of NPH insulin and the long-acting analogues has been suggested, but it remains unclear whether this is also true for obese patients with type 2 diabetes. In our recently published prospective study comparing the effect of NPH insulin, insulin detemir (NN304) [B29Lys(e-tetradecanoyl),desB30 human insulin] and insulin glargine (A21Gly,B31Arg,B32Arg human insulin) injected at bedtime in patients with type 2 diabetes [2], each patient was sequentially treated with all three longacting insulin preparations. Comparable predefined glucose targets were achieved at midnight (00:00 hours) and in the morning (at 07:00 hours) with all three insulin preparations tested; none of them could totally prevent the rise of glucose between 05:00 and 08:00 hours. As mentioned (but not shown) in our communication, a trend for increased analogue (compared with NPH) insulin dose requirements (especially in obese patients on high total doses) to reach glucose targets was observed. The difference was significant in patients with a BMI of >30 kg/m, as shown in Table 1. In patients with type 2 diabetes, it has previously been reported that a higher dose of insulin analogues relative to NPH insulin is required to achieve similar glucose control, e.g. in the Treat-to-Target Trial, in which doses of insulin glargine were higher than those of NPH [3]. An increased insulin dose requirement compared with NPH insulin in patients with type 2 diabetes has also been reported for insulin detemir [4, 5]. Whereas such differences have not been found in all studies (e.g. in the LANMET study [6]), to the best of our knowledge, the opposite, i.e. a lower insulin dose requirement of the long-acting analogues compared with NPH insulin in patients with type 2 diabetes, has not been reported. Good glycaemic control and prevention of cardiovascular disease remain major goals when treating patients with type 2 diabetes. Lifestyle changes are difficult to achieve, C. Schmid Department of Internal Medicine, Division of Endocrinology and Diabetes, University Hospital Zurich, Zurich, Switzerland

Glycemic profile and effectiveness and safety of insulin therapy in septic patients. Is the blood glucose level sufficient?

Hyperglycemia in sepsis is managed by intensive insulin therapy, which can cause hypoglycemia. The aim of the study was to evaluate the glycemic profile as well as safety and effectiveness of a nurse-controlled insulin therapy protocol in patients with severe sepsis and septic shock. The study included 16 septic patients who died (nonsurvivors) and 61 septic patients who survived. Glycemia was measured every 4 h, and the dose of insulin infusion was adjusted to maintain glycemia of 4.4 mmol/l to 8.3 mmol/l. We analyzed glycemia levels and daily variations, insulin dose, episodes of hypo- and hyperglycemia. Nonsurvivors and survivors had similar mean glycemia levels (7.38 vs. 7.08 mmol/l; p = 0.20) and insulin requirements (median [Me] = 26.9 vs. 23.9 units/d; p = 0.22; Me = 1.7 vs. 1.4 units/h; p = 0.25). Daily glycemia variation (Me = 4.81 vs. 3.03 mmol/l; p <0.001), episodes of hypoglycemia (18.8% vs. 3.3%; p = 0.02), spontaneous severe hypoglycemia (12.5% vs. 0%; p = 0.006) and hyperglycemia (75.0% vs. 45.9%; p = 0.04) were higher and more frequent in nonsurvivors. Three of 5393 blood samples (0.05%) met severe insulin-induced hypoglycemia criteria, and 74.4% of samples met the recommended range of 4.4-8.3 mmol/l. Patients who died experienced more episodes of hyperglycemia, spontaneous hypoglycemia and greater variation in the daily glycemia level. Daily glycemia variation is more reliable than a mean glycemic level in evaluating glucose homeostasis in septic patients. Few episodes of severe insulin-induced hypoglycemia occurred while using the nurse-controlled insulin therapy protocol.

The hospital pharmacist: an integral part of the hyperglycaemic management team

To identify the many roles of the hospital pharmacist in improving the health and outcomes for in-patients experiencing episodes of hyperglycaemia. Information for this article was selected from articles found on MEDLINE between 1998 and 2008 on the topics of hospital management of hyperglycaemia and type 2 diabetes. The article was further developed according to the clinical experiences of the author. When discussing the identification and treatment of hyperglycaemia in hospitalized patients, it is important to include the many aspects of glycaemic control that can be provided by hospital pharmacists. These include tasks such as patient screening and identification, monitoring glycaemic parameters, documenting therapy and therapeutic end points, and evaluating prescribing habits. Risk evaluation, guideline implementation, and a coordinated multi-disciplinary approach to discharge planning can be used to improve diabetes management by incorporating the entire hospital health-care team in patient care and education. Hospital pharmacists should develop and implement protocolized care for the management of patients with hyperglycaemia throughout the institution in order to optimize the efficacy and safety of insulin therapy.