Evidence on outcomes of treating type 1 diabetes (T1D) with long-acting basal insulins in low-resourced settings is lacking. This study aimed to evaluate the impact of switching children and youth with T1D in the low-income country of Mali from human insulin via syringe to long-acting biosimilar insulin glargine delivered by reusable pens combined with short-acting insulin via syringe.

A two-group parallel design randomised trial was conducted enrolling 260 youth aged <25 years, diagnosed with T1D for ≥12 months without prior use of analogue insulin. Youth were randomised 1:1 to either continue receiving current therapy or switch to analogue insulin. The primary outcome was HbA1c, collected at baseline and 3-monthly for 12 months.

Primary outcome data were available for 130 (100%) youth in the intervention group and 128 (98.5%) in the control group. Over the 12-month study period, mean HbA1c decreased from 103 to 65 mmol/mol (11.6%-8.1%) (p < 0.001) in the intervention group and from 101 to 93 mmol/mol (11.4% to 10.7%) in the control group (p < 0.01), an absolute difference of 30 mmol/mol (95% CI: -37, -24) (p < 0.001). The proportion of participants with HbA1c ≥130 mmol/mol (≥14%) decreased from 38.5% to 0% in the intervention group, versus 40.6% to 21.9% in the control group.

Switching to a basal-bolus insulin regimen including biosimilar glargine resulted in marked improvements in HbA1c and diabetic ketoacidosis episodes. With relevant training, resources, and support, use of long-acting analogue insulin for treating T1D in Mali was feasible and acceptable to participants and healthcare professionals.

The objective of this clinical practice guideline is to provide updated and new evidence-based recommendations for the comprehensive care of persons with diabetes mellitus to clinicians, diabetes-care teams, other health care professionals and stakeholders, and individuals with diabetes and their caregivers.

The American Association of Clinical Endocrinology selected a task force of medical experts and staff who updated and assessed clinical questions and recommendations from the prior 2015 version of this guideline and conducted literature searches for relevant scientific papers published from January 1, 2015, through May 15, 2022. Selected studies from results of literature searches composed the evidence base to update 2015 recommendations as well as to develop new recommendations based on review of clinical evidence, current practice, expertise, and consensus, according to established American Association of Clinical Endocrinology protocol for guideline development.

This guideline includes 170 updated and new evidence-based clinical practice recommendations for the comprehensive care of persons with diabetes. Recommendations are divided into four sections: (1) screening, diagnosis, glycemic targets, and glycemic monitoring; (2) comorbidities and complications, including obesity and management with lifestyle, nutrition, and bariatric surgery, hypertension, dyslipidemia, retinopathy, neuropathy, diabetic kidney disease, and cardiovascular disease; (3) management of prediabetes, type 2 diabetes with antihyperglycemic pharmacotherapy and glycemic targets, type 1 diabetes with insulin therapy, hypoglycemia, hospitalized persons, and women with diabetes in pregnancy; (4) education and new topics regarding diabetes and infertility, nutritional supplements, secondary diabetes, social determinants of health, and virtual care, as well as updated recommendations on cancer risk, nonpharmacologic components of pediatric care plans, depression, education and team approach, occupational risk, role of sleep medicine, and vaccinations in persons with diabetes.

This updated clinical practice guideline provides evidence-based recommendations to assist with person-centered, team-based clinical decision-making to improve the care of persons with diabetes mellitus.

The destruction of β-cells of the pancreas leads to either insulin shortage or the complete absence of insulin, which in turn causes diabetes Mellitus. For treating diabetes, many trials have been conducted since the 19th century until now. In ancient times, insulin from an animal's extract was taken to treat human beings. However, this resulted in some serious allergic reactions. Therefore, scientists and researchers have tried their best to find alternative ways for managing diabetes with progressive advancements in biotechnology. However, a lot of research trials have been conducted, and they discovered more progressed strategies and approaches to treat type I and II diabetes with satisfaction. Still, investigators are finding more appropriate ways to treat diabetes accurately. They formulated insulin analogs that mimic the naturally produced human insulin through recombinant DNA technology and devised many methods for appropriate delivery of insulin. This review will address the following questions: What is insulin preparation? How were these devised and what are the impacts (both positive and negative) of such insulin analogs against TIDM (type-I diabetes mellitus) and TIIDM (type-II diabetes mellitus)? This review article will also demonstrate approaches for the delivery of insulin analogs into the human body and some future directions for further improvement of insulin treatment.

This article describes a cross-sectional study involving 401 adults with type 1 diabetes treated with insulin glargine in Minas Gerais, Brazil. Health-related quality of life was assessed, and worse scores were found to be associated with a low level of education, self-perceived health reported as poor/very poor, being bedridden and not physically exercised, having seen a doctor more than four times in the past year, and having reported comorbidities and episodes of hypoglycemia.

Hypoglycemia is a common complication in patients with diabetes, mainly in those treated with insulin, sulfonylurea, or glinide. Impairments in counterregulatory responses and hypoglycemia unawareness constitute the main risk factors for severe hypoglycemia. Episodes of hypoglycemia are associated with physical and psychological morbidity. The fear of hypoglycemia constitutes a barrier that impairs the patient's ability to reach good glycemic control. To prevent hypoglycemia, much effort must be invested in patient education regarding risk factors, warning signs, and treatment of hypoglycemia at an early stage, together with setting personalized goals for glycemic control. In this review, we present a comprehensive update on the treatment and prevention of hypoglycemia in type 1 and type 2 diabetic patients.

The number of individuals with diabetes and pre-diabetes is constantly increasing. These conditions are overrepresented in patients undergoing percutaneous coronary intervention and are associated with adverse prognosis. Optimal glycaemic control during an acute coronary syndrome is a relevant factor for the improvement of longer-term outcomes. In addition, the implementation of newer glucose-lowering drugs with proven cardiovascular benefits has a remarkable impact on recurrence of events, hospitalisations for heart failure and mortality. In this narrative review, we outline the current state-of-the art recommendations for glucose-lowering therapy in patients with diabetes undergoing coronary intervention. In addition, we discuss the most recent evidence-based indications for revascularisation in patients with diabetes as well as the targets for glycaemic control post revascularisation. Current treatment goals for concomitant risk factor control are also addressed. Lastly, we acknowledge the presence of knowledge gaps in need of future research.

We aimed to assess the comparative efficacy and safety of second-generation basal insulins (glargine U300 and degludec U100) vs. neutral protamine Hagedorn (NPH) and first-generation basal insulins (glargine U100 and detemir) in type 1 diabetes (T1D) adults.PubMed, the Cochrane Library, ClinicalTrials.gov, and Google Scholar (until January 2021) were systematically searched. Randomized controlled trials (RCTs) with ≥ 12 weeks of follow-up comparing efficacy (HbA_1c) or safety (hypoglycemia and weight gain) between second-generation basal insulins vs. other basal insulins in T1D adults were included. Bayesian network meta-analyses were used to estimate risk ratio, hazard ratio, and mean difference. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to appraise evidence certainty.Eighteen RCTs (≥ 24 weeks of follow-up) involving 7283 randomized participants were included for main analysis. Moderate to high certainty evidence suggested that second-generation basal insulins showed equivalent HbA_1c reduction compared with NPH and first-generation basal insulins. Compared with second-generation basal insulins, low to high certainty evidence suggested that NPH was associated with a higher risk of patients experiencing severe hypoglycemia; NPH and first-generation basal insulins were associated with a higher rate of nocturnal confirmed hypoglycemic events. For the weight gain, glargine U300 was comparable to detemir (low certainty), but degludec U100 was greater than detemir (moderate certainty).In conclusion, second-generation basal insulins maintained equivalent efficacy of glycemic control (moderate to high certainty), with differences in safety (low to high certainty) compared with NPH and first-generation basal insulins during ≥ 24 weeks of follow-up in T1D adults.

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association (KDA) updated the previous clinical practice guidelines for Korean adults with diabetes and prediabetes and published the seventh edition in May 2021. We performed a comprehensive systematic review of recent clinical trials and evidence that could be applicable in real-world practice and suitable for the Korean population. The guideline is provided for all healthcare providers including physicians, diabetes experts, and certified diabetes educators across the country who manage patients with diabetes or the individuals at the risk of developing diabetes mellitus. The recommendations for screening diabetes and glucose-lowering agents have been revised and updated. New sections for continuous glucose monitoring, insulin pump use, and non-alcoholic fatty liver disease in patients with diabetes mellitus have been added. The KDA recommends active vaccination for coronavirus disease 2019 in patients with diabetes during the pandemic. An abridgement that contains practical information for patient education and systematic management in the clinic was published separately.

Background: Diabetes mellitus rates continue to rise, which coupled with increasing costs of associated complications has appreciably increased global expenditure in recent years. The risk of complications are enhanced by poor glycaemic control including hypoglycaemia. Long-acting insulin analogues were developed to reduce hypoglycaemia and improve adherence. Their considerably higher costs though have impacted their funding and use. Biosimilars can help reduce medicine costs. However, their introduction has been affected by a number of factors. These include the originator company dropping its price as well as promoting patented higher strength 300 IU/ml insulin glargine. There can also be concerns with different devices between the manufacturers. Objective: To assess current utilisation rates for insulins, especially long-acting insulin analogues, and the rationale for patterns seen, across multiple countries to inform strategies to enhance future utilisation of long-acting insulin analogue biosimilars to benefit all key stakeholders. Our approach: Multiple approaches including assessing the utilisation, expenditure and prices of insulins, including biosimilar insulin glargine, across multiple continents and countries. Results: There was considerable variation in the use of long-acting insulin analogues as a percentage of all insulins prescribed and dispensed across countries and continents. This ranged from limited use of long-acting insulin analogues among African countries compared to routine funding and use across Europe in view of their perceived benefits. Increasing use was also seen among Asian countries including Bangladesh and India for similar reasons. However, concerns with costs and value limited their use across Africa, Brazil and Pakistan. There was though limited use of biosimilar insulin glargine 100 IU/ml compared with other recent biosimilars especially among European countries and Korea. This was principally driven by small price differences in reality between the originator and biosimilars coupled with increasing use of the patented 300 IU/ml formulation. A number of activities were identified to enhance future biosimilar use. These included only reimbursing biosimilar long-acting insulin analogues, introducing prescribing targets and increasing competition among manufacturers including stimulating local production. Conclusions: There are concerns with the availability and use of insulin glargine biosimilars despite lower costs. This can be addressed by multiple activities.

Insulin glargine is a long-acting analogue of human insulin that has been used to manage hyperglycemia in patients with diabetes mellitus (DM) for nearly 20 years. Insulin glargine has a relatively constant concentration-time profile that mimics basal levels of insulin and allows for once-daily administration. MYL-1501D is a biosimilar insulin glargine designed to offer greater access of insulin glargine to patients, with comparable efficacy and safety to the marketed reference product. We conducted a comprehensive panel of studies based on a formal analysis of critical quality attributes to characterize the structural and functional properties of MYL-1501D and reference insulin glargine products available in the United States and European Union. MYL-1501D was comprehensively shown to have high similarity to the reference products in terms of protein structure, metabolic activity (both in vitro cell-based assays and in vivo rabbit bioassays), and in vitro cell-based assays for mitogenic activity. The structural analyses demonstrated that the primary protein sequence was identical, and secondary and tertiary structures are similar between the proposed biosimilar and the reference products. Insulin receptor binding affinity and phosphorylation studies also established analytical similarity. MYL-1501D demonstrated high similarity in different metabolic assays of glucose uptake, adipogenesis activity, and inhibition of stimulated lipolysis. Rabbit bioassay studies showed MYL-1501D and EU-approved insulin glargine are highly similar to US-licensed insulin glargine. These product quality studies show high similarity between MYL-1501D and licensed or approved insulin glargine products and suggest the potential of MYL-1501D as an alternative cost-effective treatment option for patients and clinicians.

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-certainty evidence). Four studies with 1013 participants reported QoL showing no true beneficial effect or harmful effect for either intervention (low-certainty evidence). Severe hypoglycaemia was observed in 122/1191 participants (10.2%) in the insulin glargine group compared with 145/1159 participants (12.5%) in the NPH insulin group (RR 0.84, 95% CI 0.67 to 1.04; 9 studies, 2350 participants; moderate-certainty evidence). No participant experienced a NFMI and one participant in the NPH insulin group experienced a NFS in the single study reporting this outcome (585 participants; low-certainty evidence). A total of 109/1131 participants (9.6%) in the insulin glargine group compared with 110/1098 participants (10.0%) in the NPH insulin group experienced SAEs (RR 1.08, 95% CI 0.63 to 1.84; 8 studies, 2229 participants; moderate-certainty evidence). Severe nocturnal hypoglycaemia was observed in 69/938 participants (7.4%) in the insulin glargine group compared with 83/955 participants (8.7%) in the NPH insulin group (RR 0.83, 95% CI 0.62 to 1.12; 6 studies, 1893 participants; moderate-certainty evidence). The MD in HbA1c comparing insulin glargine with NPH insulin was 0.02%, 95% CI -0.1 to 0.1; 9 studies, 2285 participants; moderate-certainty evidence. Insulin detemir versus insulin glargine (2 RCTs),insulin degludec versus insulin detemir (2 RCTs), insulin degludec versus insulin glargine (4 RCTs): there was no evidence of a clinically relevant difference for all main outcomes comparing (ultra-)long-acting insulin analogues with each other. For all outcomes none of the comparisons indicated differences in tests of interaction for children versus adults.

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.

Insulin treatment in children and adolescents with autoimmune type 1 diabetes has changed tremendously in the last 20 years with the knowledge of DCCT trial regarding near-normal glucose levels on the micro- and macrovascular outcome. Intensified insulin therapy is now standard of care. Carb counting however was introduced systematically only recently in several countries. In industrialized countries most patients in this age group are treated with continuous subcutaneous insulin injections. Nowadays this is combined with continuous subcutaneous glucose measurement commencing sensor-augmented pump therapy. Predictive low glucose suspend reduces the frequency of hypoglycemic events. Still not available for children is a commercially available closed loop system. However, treatment goals are still frequently not reached especially in the group of adolescents. Therefore several additive drugs are tested to improve treatment results. There are new insulins with faster and longer action profile in the pipeline to better mimic physiologic insulin profiles. Smart insulins may be able to mimic reaction on blood sugar levels. The broad facet of treatment modalities helps pediatric diabetes teams to individualize therapy and so improve patients' health-related quality of life.

Intensive insulin therapy (IIT) aims at achieving near-normal glycemic control and usually uses a basal-bolus (BB) schema to mimic physiologic insulin secretion.

The treatment burden of IIT should be outweighed by improved glycemic control and reduction of chronic complications, but reviews summarizing the effects of IIT in subjects with T1DM and T2DM in glycated hemoglobin, hypoglycemia, insulin doses, and weight are limited.

We performed a PubMed search to identify relevant randomized control trials (RCTs) comparing IIT and conventional insulin treatment in T1DM and T2DM subjects and addressing glycated hemoglobin, hypoglycemia, insulin requirements, and weight.

We have identified 11 RCTs in T1DM subjects, published years ago and very heterogenous in design. Throughout the studies there was a consistent superiority of IIT in glycated hemoglobin reduction, a higher rate of severe hypoglycemia and more weight gain in the IIT group without a clear effect on insulin doses. We have identified 2 RCTs in T2DM subjects, only one of them using a definite BB schema in the IIT group. IIT induced more hypoglycemia and better HbA1c, but not more weight gain.

IIT is the best option for treatment of subjects with T1DM in HbA1c reduction with a cost in the rate of hypoglycemia and weight gain. In subjects with T2DM, IIT also yields improvement in HbA1c versus conventional treatment, also at the cost of more hypoglycemic episodes, but not of higher weight gain. RCT treatment arms did not only differ in the insulin schema, but also in treatment goals, therapeutic education, and frequency of clinical visits among other characteristics. However, most evidence was gained using a BB insulin schema in the intensive arm and it is likely that the insulin schema had a relevant contribution in the results.

To assess effects of basal-bolus insulin treatment (BBIT) with lispro and neutral protamine Hagedorn (NPH) insulins, compared with NPH insulin alone, on serum fructosamine concentration (SFC) and postprandial blood glucose concentration (BGC) in dogs with clinically well-controlled diabetes mellitus and postprandial hyperglycemia fed a high insoluble fiber-content diet.

6 client-owned dogs with diabetes mellitus.

Blood samples were collected for BGC and SFC measurement in hospitalized dogs just before feeding and routine SC NPH insulin administration (time 0); samples were collected for BGC measurement every 30 minutes for 2 hours, then every 2 hours for up to 10 additional hours. Postprandial hyperglycemia was identified when BGC 30 minutes after insulin administration exceeded BGC at time 0 or the 1-hour time point. For BBIT, owners were instructed to continue NPH insulin administration at the usual dosage at home (q 12 h, with feeding) and to administer lispro insulin (0.1 U/Kg, SC) separately at the time of NPH injections. Two weeks later, SFC and BGC measurements were repeated; results at the start and end of the study were compared statistically.

Median SFC was significantly higher at the start (400 μmol/L) than at the end (390 μmol/L) of the study. Median 1-hour (313 mg/dL) and 1.5-hour (239 mg/dL) BGC measurements at the start of the study were significantly higher than those at the end of the study (117 and 94 mg/dL, respectively).

In this sample of dogs with well-controlled diabetes mellitus, addition of lispro insulin to an existing treatment regimen of NPH insulin and dietary management significantly decreased postprandial BGCs. Further study of BBIT for dogs with diabetes mellitus is warranted.

To report phase 1 bioequivalence results comparing MYL-1501D, US reference insulin glargine (US IG), and European reference insulin glargine (EU IG).

The double-blind, randomized, three-way crossover study compared the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of MYL-1501D, US IG and EU IG. In total, 114 patients with type 1 diabetes (T1DM) received 0.4 U/kg of each study treatment under automated euglycaemic clamp conditions. Insulin metabolite M1 concentrations, insulin glargine (IG) and glucose infusion rates (GIRs) were assessed over 30 hours. Primary PK endpoints were area under the serum IG concentration-time curve from 0 to 30 hours (AUCins.0-30h ) and maximum serum IG concentration (Cins.max ). Primary PD endpoints were area under the GIR-time curve from 0 to 30 hours (AUCGIR0-30h ) and maximum GIR (GIRmax ).

Bioequivalence among MYL-1501D, US IG and EU IG was demonstrated for the primary PK and PD endpoints. Least squares mean ratios were close to 1, and 90% confidence intervals were within 0.80 to 1.25. The PD GIR-time profiles were nearly superimposable. There were no noticeable differences in the safety profiles of the three treatments, and no serious adverse events were reported.

Equivalence with regard to PK and PD characteristics was shown among MYL-1501D, US IG and EU IG in patients with T1DM, and each treatment was well tolerated and safe.

Here, we review insulin management options and strategies in nonpregnant adult patients with type 1 diabetes mellitus (T1DM). Most patients with T1DM should follow a regimen of multiple daily injections of basal/bolus insulin, but those not meeting individual glycemic targets or those with frequent or severe hypoglycemia or pronounced dawn phenomenon should consider continuous subcutaneous insulin infusion. The latter treatment modality could also be an alternative based on patient preferences and availability of reimbursement. Continuous glucose monitoring may improve glycemic control irrespective of treatment regimen. A glycemic target of glycated hemoglobin < 7% (53 mmol/mol) is appropriate for most nonpregnant adults. Basal insulin analogues with a reduced peak profile and an extended duration of action with lower intraindividual variability relative to neutral protamine Hagedorn insulin are preferred. The clinical advantages of basal analogues compared with older basal insulins include reduced injection burden, better efficacy, lower risk of hypoglycemic episodes (especially nocturnal), and reduced weight gain. For prandial glycemic control, any rapid-acting prandial analogue (aspart, glulisine, lispro) is preferred over regular human insulin. Faster-acting insulin aspart is a relatively new option with the advantage of better postprandial glucose coverage. Frequent blood glucose measurements along with patient education on insulin dosing based on carbohydrate counting, premeal blood glucose, and anticipated physical activity is paramount, as is education on the management of blood glucose under different circumstances.Plain Language Summary: Plain language summary is available for this article.

Meta-analyses of clinical trials comparing CSII with traditional insulin injections usually show a small, but significant advantage of CSII with respect to HbA1c and risk of severe hypoglycemia. On the other hand, CSII is associated with a small, but relevant risk of ketoacidosis, mainly due to malfunction of insulin pump and/or catheter occlusion. During last time, the technology of insulin pumps and infusion sets has improved as the profound evolution in type and schemes with traditional insulin injections. Aim of the present study is to update previous meta-analyses comparing CSII with traditional insulin injections in subjects with type 1 diabetes. Specific subgroup analyses were designed for assessing the effects of CSII in comparison with basal-bolus MDI, with short-acting analogues as bolus and long-acting analogues as basal insulin. In addition, an exploratory analysis was performed to verify the effect of CSII in insulin-naïve patients with type 1 diabetes. The present analysis includes all randomized clinical trials comparing CSII with traditional injections in type 1 diabetes, with a duration of at least 12 weeks. Animal studies were excluded, whereas no language or date restriction was imposed. If duplicate publications of a single trial were present, the paper containing more adequate information was considered as principal publication. In trials comparing CSII with basal-bolus MDI, performed before the introduction of rapid-acting analogues, regular human insulin was used for CSII, and as prandial insulin in control groups. CSII was associated with a significant reduction of A1c, in comparison with MDI, irrespective of the use of either human insulin or rapid-acting analogues. However, in trials with rapid-acting analogue the advantage of CSII was significantly smaller than in trials with regular human insulin (HbA1c difference: - 0.29[- 0.46; - 0.13] vs - 1.93[- 1.84; - 0.42]%; p = 0.02). Different rapid-acting analogues provided similar results (HbA1c reduction vs MDI: - 0.25 [- 0.48; - 0.02]%, p = 0.03, and - 0.29 [- 0.49; - 0.09]%, p = 0.005, for lispro and aspart, respectively). In addition, in trials comparing CSII with basal-bolus MDI, CSII reduced HbA1c to a similar extent irrespective of the use of either NPH or long-acting analogues as basal insulin in the control groups (HbA1c reduction vs MDI: - 0.31 [- 0.55; - 0.06]%, p = 0.01, and - 0.20 [- 0.38; - 0.03]%, p = 0.02, for NPH and long-acting analogues, respectively. With respect to severe hypoglycemia, CSII did not produce a significant reduction of risk in comparison with traditional insulin injections. Conversely, CSII was associated with a significant increase in the incidence of reported diabetic ketoacidosis (DKA). Notably, the increased risk of DKA was significant in trials comparing CSII with conventional insulin therapy, whereas only a nonsignificant trend toward an increased risk was observed in comparisons with basal-bolus MDI. Only two trials comparing CSII with basal-bolus MDI, both using rapid-acting analogues, were performed on insulin-naïve type 1 diabetic patients. When those two trials were analyzed separately, CSII did not produce any relevant effect on HbA1c (difference from control: - 0.10[- 0.38; + 0.17]%; p = 0.46). No meta-analysis could be performed on either severe hypoglycemia or DKA, which were not reported by one of the two trials. CSII seems to produce a small improvement in HbA1c in patients with type 1 diabetes inadequately controlled with MDI. This apparent effect, which could be partly due to publication bias, is smaller when MDI is properly performed using basal-bolus schemes with short-acting insulin analogues. Other outcomes different from HbA1c (such as quality of life) could be relevant for the choice of CSII instead of MDI. In addition, further studies are needed to better define the profile of patients who could benefit most from CSII.

To evaluate if the lowest target level for glycated haemoglobin (HbA_1c) of <6.5% is associated with lower risk for retinopathy and nephropathy than less tight control in children and adults with type 1 diabetes.

Population based cohort study.

Swedish National Diabetes Registry, 1 January 1998 to 31 December 2017.

10 398 children and adults with type 1 diabetes followed from diagnosis, or close thereafter, until end of 2017.

Relative risk (odds ratios) for retinopathy and nephropathy for different mean levels of HbA_1c.

Mean age of participants was 14.7 years (43.4% female), mean duration of diabetes was 1.3 years, and mean HbA_1c level was 8.0% (63.4 mmol/mol). After adjustment for age, sex, duration of diabetes, blood pressure, blood lipid levels, body mass index, and smoking, the odds ratio for mean HbA_1c <6.5% (<48 mmol/mol) compared with 6.5-6.9% (48-52 mmol/mol) for any retinopathy (simplex or worse) was 0.77 (95% confidence interval 0.56 to 1.05, P=0.10), for preproliferative diabetic retinopathy or worse was 3.29 (0.99 to 10.96, P=0.05), for proliferative diabetic retinopathy was 2.48 (0.71 to 8.62, P=0.15), for microalbuminuria or worse was 0.98 (0.60 to 1.61, P=0.95), and for macroalbuminuria was 2.47 (0.69 to 8.87, P=0.17). Compared with HbA_1c levels 6.5-6.9%, HbA_1c levels 7.0-7.4% (53-57 mmol/mol) were associated with an increased risk of any retinopathy (1.31, 1.05 to 1.64, P=0.02) and microalbuminuria (1.55, 1.03 to 2.32, P=0.03). The risk for proliferative retinopathy (5.98, 2.10 to 17.06, P<0.001) and macroalbuminuria (3.43, 1.14 to 10.26, P=0.03) increased at HbA_1c levels >8.6% (>70 mmol/mol). The risk for severe hypoglycaemia was increased at mean HbA_1c <6.5% compared with 6.5-6.9% (relative risk 1.34, 95% confidence interval 1.09 to 1.64, P=0.005).

Risk of retinopathy and nephropathy did not differ at HbA_1c levels <6.5% but increased for severe hypoglycaemia compared with HbA_1c levels 6.5-6.9%. The risk for severe complications mainly occurred at HbA_1c levels >8.6%, but for milder complications was increased at HbA_1c levels >7.0%.

Since its discovery almost a century ago, there have been numerous advancements in the formulations of insulin. The newer insulin analogs have structural modifications with the goal of altering pharmacokinetics to achieve either quick onset and offset of action (mealtime bolus analogs), or a prolonged steady action (basal analogs). These analogs offer many advantages over older human insulins but are several-fold more expensive. The aim of this review is to evaluate reasons for the exorbitant price of the newer insulins, to examine the evidence regarding their clinical advantages and to make value-based prescribing recommendations.

The higher cost of newer insulins cannot be justified based on drug development or manufacturing costs. Compared with older insulins, newer analogs do not offer significant advantage in achieving hemoglobin A1c targets, but they reduce risk of hypoglycemia. The reductions in hypoglycemia are relatively modest and most apparent in those with type 1 diabetes, possibly because these individuals are more prone to hypoglycemia.

When cost considerations are important, the older insulins (regular and NPH insulin) can be used safely and effectively for most individuals with type 2 diabetes who have a low risk of hypoglycemia.