insulin--isophane and insulin-degludec

People with type 1 diabetes mellitus (T1DM) need treatment with insulin for survival. Whether any particular type of (ultra-)long-acting insulin provides benefit especially regarding risk of diabetes complications and hypoglycaemia is unknown.. To compare the effects of long-term treatment with (ultra-)long-acting insulin analogues to NPH insulin (neutral protamine Hagedorn) or another (ultra-)long-acting insulin analogue in people with type 1 diabetes mellitus.. We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Scopus, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform and the reference lists of systematic reviews, articles and health technology assessment reports. We explored the US Food and Drug Administration (FDA) and European Medical Agency (EMA) web pages. We asked pharmaceutical companies, EMA and investigators for additional data and clinical study reports (CSRs). The date of the last search of all databases was 24 August 2020.. We included randomised controlled trials (RCTs) with a duration of 24 weeks or more comparing one (ultra-)long-acting insulin to NPH insulin or another (ultra-)long-acting insulin in people with T1DM.. Two review authors assessed risk of bias using the new Cochrane 'Risk of bias' 2 (RoB 2) tool and extracted data. Our main outcomes were all-cause mortality, health-related quality of life (QoL), severe hypoglycaemia, non-fatal myocardial infarction/stroke (NFMI/NFS), severe nocturnal hypoglycaemia, serious adverse events (SAEs) and glycosylated haemoglobin A1c (HbA1c). We used a random-effects model to perform meta-analyses and calculated risk ratios (RRs) and odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) and 95% prediction intervals for effect estimates. We evaluated the certainty of the evidence applying the GRADE instrument.. We included 26 RCTs. Two studies were unpublished. We obtained CSRs, clinical study synopses or both as well as medical reviews from regulatory agencies on 23 studies which contributed to better analysis of risk of bias and improved data extraction. A total of 8784 participants were randomised: 2428 participants were allocated to NPH insulin, 2889 participants to insulin detemir, 2095 participants to insulin glargine and 1372 participants to insulin degludec. Eight studies contributing 21% of all participants comprised children. The duration of the intervention varied from 24 weeks to 104 weeks. Insulin degludec versus NPH insulin: we identified no studies comparing insulin degludec with NPH insulin. Insulin detemir versus NPH insulin (9 RCTs): five deaths reported in two studies including adults occurred in the insulin detemir group (Peto OR 4.97, 95% CI 0.79 to 31.38; 9 studies, 3334 participants; moderate-certainty evidence). Three studies with 870 participants reported QoL showing no true beneficial or harmful effect for either intervention (low-certainty evidence). There was a reduction in severe hypoglycaemia in favour of insulin detemir: 171/2019 participants (8.5%) in the insulin detemir group compared with 138/1200 participants (11.5%) in the NPH insulin group experienced severe hypoglycaemia (RR 0.69, 95% CI 0.52 to 0.92; 8 studies, 3219 participants; moderate-certainty evidence). The 95% prediction interval ranged between 0.34 and 1.39. Only 1/331 participants in the insulin detemir group compared with 0/164 participants in the NPH insulin group experienced a NFMI (1 study, 495 participants; low-certainty evidence). No study reported NFS. A total of 165/2094 participants (7.9%) in the insulin detemir group compared with 102/1238 participants (8.2%) in the NPH insulin group experienced SAEs (RR 0.95, 95% CI 0.75 to 1.21; 9 studies, 3332 participants; moderate-certainty evidence). Severe nocturnal hypoglycaemia was observed in 70/1823 participants (3.8%) in the insulin detemir group compared with 60/1102 participants (5.4%) in the NPH insulin group (RR 0.67, 95% CI 0.39 to 1.17; 7 studies, 2925 participants; moderate-certainty evidence). The MD in HbA1c comparing insulin detemir with NPH insulin was 0.01%, 95% CI -0.1 to 0.1; 8 studies, 3122 participants; moderate-certainty evidence. Insulin glargine versus NPH insulin (9 RCTs): one adult died in the NPH insulin group (Peto OR 0.14, 95% CI 0.00 to 6.98; 8 studies, 2175 participants; moderate-cert. Comparing insulin detemir with NPH insulin for T1DM showed lower risk of severe hypoglycaemia in favour of insulin detemir (moderate-certainty evidence). However, the 95% prediction interval indicated inconsistency in this finding. Both insulin detemir and insulin glargine compared with NPH insulin did not show benefits or harms for severe nocturnal hypoglycaemia. For all other main outcomes with overall low risk of bias and comparing insulin analogues with each other, there was no true beneficial or harmful effect for any intervention. Data on patient-important outcomes such as QoL, macrovascular and microvascular diabetic complications were sparse or missing. No clinically relevant differences were found between children and adults.

Topics: Adolescent; Adult; Bias; Child; Child, Preschool; Confidence Intervals; Diabetes Mellitus, Type 1; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Male; Myocardial Infarction; Quality of Life; Randomized Controlled Trials as Topic; Stroke; Young Adult

To revisit the data analysis used to inform National Institute of Health and Care Excellence (NICE) NG17 guidance for initiating basal insulin in adults with type 1 diabetes mellitus (diabetes).. We replicated the data, methodology and analysis used by NICE diabetes in the NG17 network meta-analysis (NMA). We expanded this data cohort to a more contemporary data set (extended 2017 NMA) and restricted the studies included to improve the robustness of the data set (restricted 2017 NMA) and in a post hoc analysis, changed the index comparator from neutral protamine Hagedorn (NPH) insulin twice daily to insulin detemir twice daily.. The absolute changes in HbA. In NG17, comparisons of basal insulins were based solely on efficacy of glycaemic control. Many of the trials used in this analysis were treat-to-target, which minimize differences in HbA

Topics: Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Network Meta-Analysis; Practice Guidelines as Topic

Evidence that antihyperglycaemic therapy is beneficial for people with type 2 diabetes mellitus is conflicting. While the United Kingdom Prospective Diabetes Study (UKPDS) found tighter glycaemic control to be positive, other studies, such as the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, found the effects of an intensive therapy to lower blood glucose to near normal levels to be more harmful than beneficial. Study results also showed different effects for different antihyperglycaemic drugs, regardless of the achieved blood glucose levels. In consequence, firm conclusions on the effect of interventions on patient-relevant outcomes cannot be drawn from the effect of these interventions on blood glucose concentration alone. In theory, the use of newer insulin analogues may result in fewer macrovascular and microvascular events.. To compare the effects of long-term treatment with (ultra-)long-acting insulin analogues (insulin glargine U100 and U300, insulin detemir and insulin degludec) with NPH (neutral protamine Hagedorn) insulin (human isophane insulin) in adults with type 2 diabetes mellitus.. For this Cochrane Review update, we searched CENTRAL, MEDLINE, Embase, ICTRP Search Portal and ClinicalTrials.gov. The date of the last search was 5 November 2019, except Embase which was last searched 26 January 2017. We applied no language restrictions.. We included randomised controlled trials (RCTs) comparing the effects of treatment with (ultra-)long-acting insulin analogues to NPH in adults with type 2 diabetes mellitus.. Two review authors independently selected trials, assessed risk of bias, extracted data and evaluated the overall certainty of the evidence using GRADE. Trials were pooled using random-effects meta-analyses.. We identified 24 RCTs. Of these, 16 trials compared insulin glargine to NPH insulin and eight trials compared insulin detemir to NPH insulin. In these trials, 3419 people with type 2 diabetes mellitus were randomised to insulin glargine and 1321 people to insulin detemir. The duration of the included trials ranged from 24 weeks to five years. For studies, comparing insulin glargine to NPH insulin, target values ranged from 4.0 mmol/L to 7.8 mmol/L (72 mg/dL to 140 mg/dL) for fasting blood glucose (FBG), from 4.4 mmol/L to 6.6 mmol/L (80 mg/dL to 120 mg/dL) for nocturnal blood glucose and less than 10 mmol/L (180 mg/dL) for postprandial blood glucose, when applicable. Blood glucose and glycosylated haemoglobin A1c (HbA1c) target values for studies comparing insulin detemir to NPH insulin ranged from 4.0 mmol/L to 7.0 mmol/L (72 mg/dL to 126 mg/dL) for FBG, less than 6.7 mmol/L (120 mg/dL) to less than 10 mmol/L (180 mg/dL) for postprandial blood glucose, 4.0 mmol/L to 7.0 mmol/L (72 mg/dL to 126 mg/dL) for nocturnal blood glucose and 5.8% to less than 6.4% HbA1c, when applicable. All trials had an unclear or high risk of bias for several risk of bias domains. Overall, insulin glargine and insulin detemir resulted in fewer participants experiencing hypoglycaemia when compared with NPH insulin. Changes in HbA1c were comparable for long-acting insulin analogues and NPH insulin. Insulin glargine compared to NPH insulin had a risk ratio (RR) for severe hypoglycaemia of 0.68 (95% confidence interval (CI) 0.46 to 1.01; P = 0.06; absolute risk reduction (ARR) -1.2%, 95% CI -2.0 to 0; 14 trials, 6164 participants; very low-certainty evidence). The RR for serious hypoglycaemia was 0.75 (95% CI 0.52 to 1.09; P = 0.13; ARR -0.7%, 95% CI -1.3 to 0.2; 10 trials, 4685 participants; low-certainty evidence). Treatment with insulin glargine reduced the incidence of confirmed hypoglycaemia and confirmed nocturnal hypoglycaemia. Treatment with insulin detemir compared to NPH insulin found an RR for severe hypoglycaemia of 0.45 (95% CI 0.17 to 1.20; P = 0.11; ARR -0.9%, 95% CI -1.4 to 0.4; 5 trials, 1804 participants; very low-certainty evidence). The Peto odds ratio for serious hypoglycaemia was 0.16, 95% CI 0.04 to 0.61; P = 0.007; ARR -0.9%, 95% CI -1.1 to -0.4; 5 trials, 1777 participants; low-certainty evidence). Treatment with detemir also reduced the incidence of confirmed hypoglycaemia and confirmed nocturnal hypoglycaemia. Information on patient-relevant outcomes such. While the effects on HbA1c were comparable, treatment with insulin glargine and insulin detemir resulted in fewer participants experiencing hypoglycaemia when compared with NPH insulin. Treatment with insulin detemir also reduced the incidence of serious hypoglycaemia. However, serious hypoglycaemic events were rare and the absolute risk reducing effect was low. Approximately one in 100 people treated with insulin detemir instead of NPH insulin benefited. In the studies, low blood glucose and HbA1c targets, corresponding to near normal or even non-diabetic blood glucose levels, were set. Therefore, results from the studies are only applicable to people in whom such low blood glucose concentrations are targeted. However, current guidelines recommend less-intensive blood glucose lowering for most people with type 2 diabetes in daily practice (e.g. people with cardiovascular diseases, a long history of type 2 diabetes, who are susceptible to hypoglycaemia or older people). Additionally, low-certainty evidence and trial designs that did not conform with current clinical practice meant it remains unclear if the same effects will be observed in daily clinical practice. Most trials did not report patient-relevant outcomes.

Topics: Bias; Diabetes Mellitus, Type 2; Hemoglobin A; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Randomized Controlled Trials as Topic

Manufacturers of insulin products for diabetes therapy have long sought ways to modify the absorption rate of exogenously administered insulins in an effort to better reproduce the naturally occurring pharmacokinetics of endogenous insulin secretion. Several mechanisms of protraction have been used in pursuit of a basal insulin, for which a low injection frequency would provide tolerable and reproducible glucose control; these mechanisms have met with varying degrees of success. Before the advent of recombinant DNA technology, development focused on modifications to the formulation that increased insulin self-association, such as supplementation with zinc or the development of preformed precipitates using protamine. Indeed, NPH insulin remains widely used today despite a frequent need for a twice-daily dosing and a relatively high incidence of hypoglycaemia. The early insulin analogues used post-injection precipitation (insulin glargine U100) or dimerization and albumin binding (insulin detemir) as methods of increasing therapeutic duration. These products approached a 24-hour glucose-lowering effect with decreased variability in insulin action. Newer basal insulin analogues have used up-concentration in addition to precipitation (insulin glargine U300), and multihexamer formation in addition to albumin binding (insulin degludec), to further increase duration of action and/or decrease the day-to-day variability of the glucose-lowering profile. Clinically, the major advantage of these recent analogues has been a reduction in hypoglycaemia with similar glycated haemoglobin control when compared with earlier products. Future therapies may bring clinical benefits through hepato-preferential insulin receptor binding or very long durations of action, perhaps enabling once-weekly administration and the potential for further clinical benefits.

Topics: Chemistry, Pharmaceutical; Diabetes Mellitus; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Lente; Insulin, Long-Acting; Recombinant Proteins

Topics: Delayed-Action Preparations; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Injections, Subcutaneous; Insulin; Insulin Detemir; Insulin, Isophane; Insulin, Long-Acting

During the past 10 years, several new basal insulin analogs have been developed. There has been for 3 years controversy on the potential increased risk for cancer with insulin glargine, which ceased with the publication of the ORIGIN trial in 2012. In insulin-treated persons with type 2 diabetes, it is usual to recommend that plasma insulin concentrations remain within a 50-200 pmol/L range in order to avoid overinsulinization, a potential causative factor for increased mitogenicity. Such concentrations are achieved when daily doses of insulin glargine or NPH insulin approximate 0.4 units/kg. However, the total plasma insulin concentrations are much greater in persons treated with insulin detemir and especially insulin degludec. These insulins derive their protracted action from the insertion of a long chain fatty acid moiety to the insulin molecule thereby increasing albumin binding. As a consequence, in persons with type 2 diabetes, stable total plasma concentrations as high as either 1600 or 6000 pmol/L are observed for insulin detemir or degludec, respectively. At present, the free to bound ratio of plasma insulin concentrations remains unknown for these two compounds. A first requirement is to understand how these insulins are eliminated or degraded and secondly to quantify the respective contributions of the free and bound fractions. Therefore, prior to early phase 2 or 3 randomized clinical trials, a better comprehension of the metabolism of all the new insulins would be invaluable.

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Topics: Diabetes Mellitus; Humans; Hypoglycemic Agents; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Topics: Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Weight Gain

Insulin degludec (IDeg) is a new insulin formulation that facilitates long-term control of glucose level in humans. In this study, we investigated the effects of IDeg on glycemic control in dogs. Its time-action profiles were monitored in healthy dogs using an artificial pancreas apparatus under euglycemic conditions. At 9.0-13.5 hr post-IDeg injection, an indistinct peak of glucose level was detected. Moreover, the action of IDeg was persistent for >20 hr. Both IDeg and neutral protamine Hagedorn insulin (NPH) lowered blood glucose concentrations in diabetic dogs, but IDeg caused postprandial hyperglycemia and a somewhat lower preprandial glucose level than that caused by NPH. IDeg might be ineffective in concurrently preventing postprandial hyperglycemia and preprandial hypoglycemia in a single-agent administration.

Topics: Animals; Blood Glucose; Diabetes Mellitus; Dog Diseases; Dogs; Dose-Response Relationship, Drug; Insulin, Isophane; Insulin, Long-Acting

The present study was a subgroup analysis of a Pan-Asian Phase 3 open-label randomized treat-to-target trial evaluating insulin degludec/insulin aspart (IDegAsp) and biphasic insulin aspart 30 (BIAsp 30) in Japanese subjects with type 2 diabetes inadequately controlled on insulin.. Eligible subjects (n = 178) were randomized (2: 1) to twice-daily (b.i.d.) IDegAsp or BIAsp 30 with or without metformin for 26 weeks, titrated to a blood glucose target of between 3.9 and <5.0 mmol/L. Changes in HbA. The results indicate that IDegAsp b.i.d. improves glycemic control and, compared with BIAsp 30, lowers the rate of nocturnal confirmed hypoglycemia.

Topics: Aged; Asian People; Biphasic Insulins; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Drug Administration Schedule; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypertension; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Nasopharyngitis; Treatment Outcome

Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of insulin degludec (70%) and insulin aspart (IAsp: 30%). Here, we compare the efficacy and safety of IDegAsp, an alternative IDegAsp formulation (AF: containing 45% IAsp), and biphasic IAsp 30 (BIAsp 30).. Sixteen-week, open-label, randomised, treat-to-target trial.. Insulin-naive subjects with type 2 diabetes (18-75 years) and a HbA1c of 7-11% were randomised to twice-daily IDegAsp (n=61), AF (n=59) or BIAsp 30 (n=62), all in combination with metformin. Insulin was administered pre-breakfast and dinner (main evening meal) and titrated to pre-breakfast and pre-dinner plasma glucose (PG) targets of 4.0-6.0 mmol/l.. Mean HbA1c after 16 weeks was comparable for IDegAsp, AF and BIAsp 30 (6.7, 6.6 and 6.7% respectively). With IDegAsp, 67% of subjects achieved HbA1c 7.0% Without confirmed hypoglycaemia in the last 4 weeks of treatment compared with 53% (AF) and 40% (BIAsp 30). Mean fasting PG was significantly lower for IDegAsp vs BIAsp 30 (treatment difference (TD): -0.99 mmol/l (95% confidence interval: -1.68; 0.29)) and AF vs BIAsp 30 (TD: -0.88 mmol/l (-1.58; -0.18)). A significant, 58% lower rate of confirmed hypoglycaemia was found for IDegAsp vs BIAsp 30 (rate ratio (RR): 0.42 (0.23; 0.75)); rates were similar for AF vs BIAsp 30 (RR: 0.92 (0.54; 1.57)). IDegAsp and AF had numerically lower rates of nocturnal confirmed hypoglycaemia vs BIAsp 30 (RR: 0.33 (0.09; 1.14) and 0.66 (0.22; 1.93) respectively).. IDegAsp provided comparable overall glycaemic control to BIAsp 30 with a significantly lower rate of hypoglycaemia.

Topics: Adolescent; Adult; Aged; Biphasic Insulins; Chemistry, Pharmaceutical; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Male; Metformin; Middle Aged; Solubility; Treatment Outcome; Young Adult

Optimizing glycemic control without risking hypoglycemia is crucial in toddlers and preschoolers with type 1 diabetes (T1D) to avoid cognitive impairment later in life. Hence, this study aims to compare glycemic parameters among toddlers and preschoolers with T1D in relation to different basal insulins. Sixty toddlers and preschoolers with T1D with mean age of 3.53 ± 1.17 years (range, 2-6) and mean diabetes duration of 9.37 ± 1.85 months were randomly assigned into three equal groups; group A received insulin degludec, group B received insulin glargine, and group C were on NPH. At baseline, the three groups were matched regarding clinical and laboratory parameters (p > 0.05). They were followed up at 3 and 6 months for insulin daily dose (IDD), hypoglycemia and severe-hypoglycemia frequency, and glycated hemoglobin (HbA1c). At the study endpoint, continuous glucose monitoring (CGM) was assessed in a random sample of 10 patients from each group. The mean time in range (TIR) of the studied cohort was 55.07 ± 24.05%, and their mean coefficient of variation (CV) was 42.82 ± 11.69%. The TIR was significantly higher in the degludec group (69.36 ± 18.54) and the glargine group (55.43 ± 26.51) than the NPH group (32.56 ± 9.11), p < 0.001. Meanwhile, the CV was significantly lower in the degludec group (35.12 ± 6.47) than the gargine (44.1 ± 13.13) and the NPH (53.8 ± 7.54) groups, p < 0.001. The insulin degludec and glargine groups had significantly lower HbA1c (p = 0.002), hypoglycemia (p = 0.006), severe hypoglycemia (p = 0.029), and IDD (p = 0.015) than the NPH group.. Insulin degludec and glargine resulted in better HbA1c and TIR with reduced hypoglycemia and IDD than NPH among toddlers and preschoolers with T1D. Moreover, CV was lowest in the insulin degludec group.. • Insulin therapy is the mainstay of T1D management. • Optimal insulin therapy for young children with T1D should provide effective glycemic.. • Insulin degludec and insulin glargine have better efficacy than NPH insulin among toddlers and preschoolers with T1D in the term of significantly lower coefficient of variation, HbA1c and IDD and significantly higher time in range. • Insulin degludec and insulin glargine have better safety in the term of less hypoglycemia and severe hypoglycemia episodes than NPH insulin among toddlers and preschoolers with T1D.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Child, Preschool; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Glargine; Insulin, Isophane

With the aim to improve current therapeutic and monitoring options for diabetic cats, the present study compared pharmacodynamic parameters of protamine zinc insulin (PZI) and insulin degludec and validated the continuous glucose monitoring system (CGMS) iPro2 with Sof-sensor and Enlite-sensor focusing on the low glycemic range. Three doses (0.1, 0.2 and 0.3IU/kg) of the two insulin preparations and the CGMS iPro2 with two different sensors were tested in six healthy cats. After each insulin administration, onset of action, time to glucose nadir and duration of action were calculated by measuring glucose concentrations with a portable blood glucose meter (PBGM). After sensor placement, paired PBGM and sensor glucose measurements were done and analytical and clinical accuracy were calculated according to the ISO 15197:2013 criteria. Onset of action, time to glucose nadir and glucose nadir were similar for both insulin formulations. Duration of action of insulin degludec was significantly longer than those of PZI at 0.1IU/kg (P=0.043) and 0.2IU/kg (P=0.043). Overall, 166/191 (87%) Sof-sensor measurements and 106/121 (88%) Enlite-sensor measurements met ISO criteria for analytical accuracy, and all sensor measurements fulfilled ISO criteria for clinical accuracy. Insulin degludec was well tolerated in healthy cats and showed longer duration of action than PZI. Further studies on the use of insulin degludec in diabetic cats might be recommended. Both sensors had good clinical accuracy, when used with the CGMS iPro2, but the analytical accuracy was below the minimum set by ISO 15197:2013.

Topics: Animals; Blood Glucose; Cats; Insulin, Isophane; Insulin, Long-Acting; Monitoring, Ambulatory

Insulin degludec/insulin aspart (IDegAsp) is a soluble coformulation of the basal analog insulin degludec and the rapid-acting prandial insulin aspart in a single injection. The present combined analysis of two Phase 3a trials compared the incidence of hypoglycemia in participants treated twice daily with IDegAsp or biphasic insulin aspart 30 (BIAsp 30).. Hypoglycemia data were analyzed from two similarly designed randomized controlled open-label treat-to-target Phase 3a clinical trials of adults with type 2 diabetes (T2D). Participants were treated twice daily with IDegAsp or BIAsp 30, with breakfast and their main evening meal.. Over 26 weeks, the rates of overall confirmed, nocturnal confirmed and severe hypoglycemic events were 19%, 57%, and 39% lower, respectively, with IDegAsp (n = 504) than BIAsp 30 (n = 364); estimated rate ratios were 0.81 (95% confidence interval [CI] 0.67, 0.98; P = 0.0341), 0.43 (95% CI 0.31, 0.59; P = 0.0001), and 0.61 (95% CI 0.26, 1.45; P = NS). The between-treatment differences were more pronounced during the maintenance period (≥16 weeks); compared with BIAsp 30, rates of overall confirmed, nocturnal confirmed and severe hypoglycemic events with IDegAsp were 0.69 (95% CI 0.55, 0.87; -31%; P = 0.0015); 0.38 (95% CI 0.25, 0.58; -62%; P < 0.0001), and 0.16 (95% CI 0.04, 0.59; -84%; P = 0.0061), respectively.. Compared with BIAsp 30 twice daily, IDegAsp twice daily provided similar improvements in glycemic control with a lower risk of hypoglycemia, particularly nocturnal hypoglycemia, in subjects with T2D previously treated with insulin.

Topics: Aged; Biphasic Insulins; Blood Glucose; Clinical Trials, Phase III as Topic; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin Aspart; Insulin, Isophane; Insulin, Long-Acting; Maintenance Chemotherapy; Male; Middle Aged; Multicenter Studies as Topic; Outcome Assessment, Health Care; Randomized Controlled Trials as Topic; Risk Factors

Basal insulins are first line injectable therapy by all international guidelines. Basal insulins can be used alone, in combination with metformin, dual or triple oral therapy, glucagon-like peptide receptor agonists, or prandial insulin. However, all basal insulins are not similar. This article proposes objective parameters, and suggests a simple checklist, using history, physical examination, and investigations, to help choose the appropriate preparation, viz degludec, detemir, glargine or NPH insulin, for persons requiring basal insulin.

Topics: Checklist; Clinical Decision-Making; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Metformin; Patient-Centered Care

In the earlier stage of type 2 diabetes, the disease can be managed by life-style modification with or without oral antidiabetic agents. However, as the disease progress, most patients eventually require insulin treatment to maintain good glycemic/control. Optimal insulin therapy should mimic the normal physiologic secretory pattern. As for ideal basal insulin, to maintain desirable pre-prandial glucose levels, duration of action should be long enough, profiles such as flat time-action and less day-to-day variation would be mandatory. This article discusses the usefulness and limitations of basal insulin therapy in type 2 diabetes comparing NPH insulin, insulin detemir, insulin glargin and insulin degludec.

Topics: Diabetes Mellitus, Type 2; Humans; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting

Topics: Animals; Biosimilar Pharmaceuticals; Chemistry, Pharmaceutical; Delayed-Action Preparations; Diabetes Mellitus; Dogs; History, 20th Century; Humans; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin Infusion Systems; Insulin, Isophane; Insulin, Long-Acting; Swine