Incidence Of Severe Hypoglycaemic Events Research Articles

Differences in insulin dosing in women with type 1 diabetes before and after the menopause.

The menstrual cycle increases insulin requirements in a subset of women with type 1 diabetes as a result of reduced insulin action through sexual hormones. If exposure to sexual hormones declines during the menopause, adaptions of insulin dosing may be required. However, there are no validated recommendations available on how to adapt insulin treatment in postmenopausal women with type 1 diabetes. The present study compared insulin dosing profiles of 630 premenopausal and 548 postmenopausal women, who had long-term type 1 diabetes and used continuous subcutaneous insulin infusion. Data were extracted from the German "Diabetes-Patienten- Verlaufsdokumentation". It was found that total daily insulin (p <0.0001), daily insulin per kilogram bodyweight (p <0.0001), total daily basal insulin (p <0.0001), daily basal insulin per kilogram bodyweight (p <0.0001) and estimated glomerular filtration rate (eGFR) (p <0.0001) were lower in postmenopausal women. Total daily bolus insulin, daily bolus insulin per kilogram, glycated haemoglobin A1, body mass index and the incidence of severe hypoglycaemic events were similar in both cohorts.Postmenopausal women with type 1 diabetes used lower insulin doses as compared with premenopausal women, whereas glycaemic control and body mass index were comparable. This observation might be explained by lower exposure to sexual hormones and lower eGFR, even though the contribution of other factors such as body composition and eating habits requires further investigation.

Evaluation of the Efficacy and Safety of an eGlycemic Management System in a Community Hospital Setting.

Glucommander is an eGlycemic management system (eGMS) for intravenous (IV) and subcutaneous (SQ) insulin therapy in hospitalized patients. The purpose of this study was to evaluate the efficacy and safety of Glucommander compared to previously utilized nomograms in the community hospital setting. This study was a retrospective, single-center cohort study comparing measures of efficacy and safety of IV and SQ insulin therapy via eGMS versus nomogram-driven IV insulin therapy followed by provider-ordered basal-bolus SQ insulin. The primary efficacy endpoint was percent of blood glucose (BG) readings per patient in target glycemic range. Safety objectives were percent of hyperglycemic events, hypoglycemic events, and severe hypoglycemic events after achieving target blood glucose range, and mean number of each event per patient. The percentage of BG readings in range was significantly higher for eGMS patients (n = 110) than comparison cohort patients (n = 108, 84.6% vs 76.8%, P < .001). Hyperglycemic events occurred for significantly fewer patients in the eGMS cohort relative to the comparison cohort (81.8% vs 92.6%, P = .03). Overall, there was no significant difference between cohorts in rate of hypoglycemic events, but hypoglycemic events while on IV insulin occurred in a significantly higher percentage of eGMS cohort patients than comparison cohort patients (30.9% vs 15.7%, P < .01). There were no significant differences in incidence of severe hypoglycemic events. Our study found that Glucommander maintained a higher percentage of BG readings in target BG range per patient compared to previously utilized nomograms. This result was driven by an improvement in hyperglycemia, but not hypoglycemia.

Increasing secular trends in height and obesity in children with type 1 diabetes: JSGIT cohort.

Recently, anthropometric indices in children with type 1 diabetes mellitus (T1DM) have begun to change. To examine secular trends in patients' anthropometric indices. Japanese children with T1DM from the 1995, 2000, 2008 and 2013 cohorts of The Japanese Study Group of Insulin Therapy for Childhood and Adolescent Diabetes. We analysed serum haemoglobin A1c (HbA1c) levels, the incidence of severe hypoglycaemic events, the types and doses of insulin, height standard deviation scores (SDS), body mass index (BMI) percentiles compared with healthy Japanese children and obesity prevalence over time. We also stratified the patients according to glycaemic control levels of <58 mmol/mol (optimal), 58-75 mmol/mol (suboptimal) and ≥75 mmol/mol (high-risk). Data for 513-978 patients from each of the cohorts were analysed. The incidence of severe hypoglycaemic events decreased over time (from 21 to 4.8/100 patient-years), while the proportion of insulin analogue doses increased (14.6% to 98.6%). In addition, patient height SDS (-0.22 to +0.17), BMI percentile (52.1 to 58.7) and obesity prevalence (2.1% to 5.1%) increased. Height SDS increased in all of the glycaemic control subgroups, while BMI percentile and obesity prevalence increased in the suboptimal and high-risk groups. Since 1995, the average height of children with T1DM has increased in parallel with increasing insulin doses. Clinicians should be aware of increased BMI in these patients and the associated risk of developing cardiovascular disease in the future.

Changes in incidence of severe hypoglycaemia in people with type 2 diabetes from 2006 to 2016: analysis based on health insurance data in Germany considering the anti-hyperglycaemic medication.

To investigate the incidence of severe hypoglycaemia over the past 10 years, taking into account changes in anti-hyperglycaemic therapy. This retrospective population-based study used German health insurance data. All adults diagnosed with documented type 2 diabetes (extrapolated to the German population: 6.6 million in 2006; 7.9 million in 2011; 8.86 million in 2016) were screened for severe hypoglycaemia. Anti-hyperglycaemic agents were identified by Anatomical Therapeutic Chemical (ATC) code. The event rate for severe hypoglycaemia was 460 per 100000 people in 2006, 490 per 100000 in 2011 and 360 per 100000 in 2016. The proportion of people with severe hypoglycaemia receiving sulfonylureas, as well as receiving combination therapy of metformin and sulfonylureas decreased from 2006 to 2016 (23.6% vs. 6.2%) Among those with severe hypoglycaemia in 2006, there were no prescriptions for dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists or sodium-glucose co-transporter 2 (SGLT2) agonists. The proportions of people with severe hypoglycaemia receiving DPP-4 inhibitors, GLP-1 receptor agonists or SGLT2 agonists in 2011 and 2016 were low. The proportion of people receiving human insulin also decreased (from 11.3% in 2006 to 10.3% in 2011 and 4.3% in 2016); the proportion of people receiving insulin analogues increased from 5.4% in 2006 to 11.5% in 2016. Therapy with mixed insulins was used by 19.7% of people with severe hypoglycaemia in 2006, by 14.0% in 2011 and by 7.3% in 2016. People undergoing therapy with insulin analogues have the highest risk of severe hypoglycaemia adjusted by age, gender, nephropathy diagnosis and year of survey [odds ratio (OR) 14.4, 95% confidence interval (95% CI) 13.5-15.5]. The incidence of severe hypoglycaemic events in Germany increased between 2006 and 2011, and decreased in 2016.

Cost-effectiveness of sensor-augmented insulin pump therapy vs continuous subcutaneous insulin infusion in patients with type 1 diabetes in the Netherlands.

AimThe aim of this study was to perform a cost-effectiveness analysis to establish the cost-effectiveness of sensor-augmented pump therapy (SAP) with automated insulin suspension vs continuous subcutaneous insulin infusion (CSII) alone in patients with type 1 diabetes in the Netherlands.Patients and methodsThe analysis was performed using the IQVIA CORE Diabetes Model (CDM) in two different patient cohorts: one with suboptimal glycemic control at baseline (mean age 27 years, mean baseline HbA1c 8.0% [64 mmol/mol]) and the other at increased risk of hypoglycemic events (mean age 18.6 years, mean baseline HbA1c 7.5% [58 mmol/mol]). Clinical input data were sourced from published literature, and the analysis was performed from the societal perspective.ResultsIn patients with suboptimal baseline glycemic control, SAP improved quality-adjusted life expectancy by 1.77 quality-adjusted life years (QALYs) vs CSII (15.54 QALYs vs 13.77 QALYs) with higher lifetime costs (EUR 189,855 vs EUR 150,366), resulting in an incremental cost-effectiveness ratio (ICER) of EUR 22,325 per QALY gained. In this cohort, sensitivity analyses showed that the influence of SAP on fear of hypoglycemia (FoH) and baseline HbA1c were key drivers of results. In patients at increased risk of hypoglycemia, the gain in quality-adjusted life expectancy with SAP vs CSII was 2.16 QALYs (16.70 QALYs vs 14.53 QALYs) with higher lifetime costs (EUR 204,013 vs EUR 171,032) leading to an ICER of EUR 15,243 per QALY gained. In this patient group, findings were most sensitive to changes in assumptions relating to the incidence of severe hypoglycemic events in the CSII arm.ConclusionFor type 1 diabetes patients in the Netherlands who do not achieve target HbA1c levels or who experience frequent severe hypoglycemic events on CSII, switching to SAP is likely to be cost-effective.

Short-acting insulin analogues versus regular human insulin for adult, non-pregnant persons with type 2 diabetes mellitus.

The use of short-acting insulin analogues (insulin lispro, insulin aspart, insulin glulisine) for adult, non-pregnant people with type 2 diabetes is still controversial, as reflected in many scientific debates. To assess the effects of short-acting insulin analogues compared to regular human insulin in adult, non-pregnant people with type 2 diabetes mellitus. For this update we searched CENTRAL, MEDLINE, Embase, the WHO ICTRP Search Portal, and ClinicalTrials.gov to 31 October 2018. We placed no restrictions on the language of publication. We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared short-acting insulin analogues to regular human insulin in the treatment of people with type 2 diabetes, who were not pregnant. Two review authors independently extracted data and assessed the risk of bias. We assessed dichotomous outcomes by risk ratios (RR), and Peto odds ratios (POR), with 95% confidence intervals (CI). We assessed continuous outcomes by mean differences (MD) with 95% CI. We assessed trials for certainty of the evidence using the GRADE approach. We identified 10 trials that fulfilled the inclusion criteria, randomising 2751 participants; 1388 participants were randomised to receive insulin analogues and 1363 participants to receive regular human insulin. The duration of the intervention ranged from 24 to 104 weeks, with a mean of about 41 weeks. The trial populations showed diversity in disease duration, and inclusion and exclusion criteria. None of the trials were blinded, so the risk of performance bias and detection bias, especially for subjective outcomes, such as hypoglycaemia, was high in nine of 10 trials from which we extracted data. Several trials showed inconsistencies in the reporting of methods and results.None of the included trials defined all-cause mortality as a primary outcome. Six trials provided Information on the number of participants who died during the trial, with five deaths out of 1272 participants (0.4%) in the insulin analogue groups and three deaths out of 1247 participants (0.2%) in the regular human insulin groups (Peto OR 1.66, 95% CI 0.41 to 6.64; P = 0.48; moderate-certainty evidence). Six trials, with 2509 participants, assessed severe hypoglycaemia differently, therefore, we could not summarise the results with a meta-analysis. Overall, the incidence of severe hypoglycaemic events was low, and none of the trials showed a clear difference between the two intervention arms (low-certainty evidence).The MD in glycosylated haemoglobin A1c (HbA1c) change was -0.03% (95% CI -0.16 to 0.09; P = 0.60; 9 trials, 2608 participants; low-certainty evidence). The 95% prediction ranged between -0.31% and 0.25%. The MD in the overall number of non-severe hypoglycaemic episodes per participant per month was 0.08 events (95% CI 0.00 to 0.16; P = 0.05; 7 trials, 2667 participants; very low-certainty evidence). The 95% prediction interval ranged between -0.03 and 0.19 events per participant per month. The results provided for nocturnal hypoglycaemic episodes were of questionable validity. Overall, there was no clear difference between the two short-acting insulin analogues and regular human insulin. Two trials assessed health-related quality of life and treatment satisfaction, but we considered the results for both outcomes to be unreliable (very low-certainty evidence).No trial was designed to investigate possible long term effects (all-cause mortality, microvascular or macrovascular complications of diabetes), especially in participants with diabetes-related complications. No trial reported on socioeconomic effects. Our analysis found no clear benefits of short-acting insulin analogues over regular human insulin in people with type 2 diabetes. Overall, the certainty of the evidence was poor and results on patient-relevant outcomes, like all-cause mortality, microvascular or macrovascular complications and severe hypoglycaemic episodes were sparse. Long-term efficacy and safety data are needed to draw conclusions about the effects of short-acting insulin analogues on patient-relevant outcomes.

Increase in the incidence of severe hypoglycaemia in people with Type 2 diabetes in spite of new drugs: analysis based on health insurance data from Germany.

To evaluate the use of new anti-hyperglycaemic agents that offer effective glycaemic control while reducing risk of hypoglycaemia, by analysing the incidence rates of severe hypoglycaemia in 2006 vs 2011 in relation to the medication. This cross-sectional, population-based study used German health insurance data. All adults diagnosed with Type 2 diabetes mellitus (extrapolated to the German population: 6.35 million in 2006 and 7.52 million in 2011) were screened for severe hypoglycaemia. Anti-hyperglycaemic agents were identified by their Anatomical Therapeutic Chemical code, and defined daily doses of each medication were calculated. The severe hypoglycaemic event rate was 460 per 100,000 people/year in 2006 and 490 per 100,000 people/year in 2011. In 2006 and 2011, 10.9% and 7.3%, respectively, of all people with severe hypoglycaemia were on sulfonylureas, while 12.7% and 9.3%, respectively, were on a combination therapy of metformin and sulfonylureas. Among those with severe hypoglycaemia, there were no prescriptions of dipeptidyl peptidase-4 inhibitors or glucagon-like peptide-1 receptor agonists in 2006, but in 2011, 1.55% and 0.17%, of those with severe hypoglycaemia were receiving the respective treatments. In 2006 vs 2011, human insulin was prescribed for 11.3% vs 10.3% of people with severe hypoglycaemia, while insulin analogues were prescribed for 5.4% vs 8.1%, and mixed human insulins for 19.7% vs 14.0% of patients with severe hypoglycaemia. People receiving insulin analogue therapy had a higher risk of severe hypoglycaemia than those receiving metformin, after adjusting for age, gender, nephropathy diagnosis and year of survey (odds ratio 14.6; CI 13.3-15.9). The incidence of severe hypoglycaemic events in Germany increased between 2006 and 2011, despite increased use of newer anti-hyperglycaemic agents and decreased use of insulins.

Antigen-based immunotherapies do not prevent progression of recent-onset autoimmune diabetes: a systematic review and meta-analysis

We performed a systematic review and meta-analysis to assess the efficacy and safety of antigen-based immunotherapies in tertiary prevention of autoimmune diabetes. We searched for randomised controlled trials testing antigen-based immunotherapies in patients with recent-onset type 1 diabetes or latent autoimmune diabetes of adults in MEDLINE, COCHRANE and EMBASE databases, trial registries, conference proceedings and reference lists of pertinent records. Primary outcomes were fasting and stimulated C-peptide (after glucagon or mixed meal stimulation). Change in glycosylated haemoglobin (HbA1c), daily insulin needs and incidence of any or severe hypoglycaemic events or severe adverse events were secondary outcomes. Fifteen studies were included in the meta-analysis. Overall, there was no difference in fasting [weighted mean difference (WMD) 0.01 nmol/L; 95 % confidence interval (CI) -0.09, 0.11; I 2 = 73 %] or mixed meal stimulated C-peptide (WMD 0.02 nmol/L/min; 95 % CI -0.08, 0.12; I 2 = 50 %) compared with placebo. Glucagon stimulated C-peptide was maintained higher (WMD 0.13 nmol/L/min; 95 % CI 0.05, 0.21; I 2 = 0 %) in patients treated with Diapep277. Moreover, there was no change in daily insulin needs (WMD 0.02 IU/kg; 95 % CI -0.04, 0.09; I 2 = 51 %) or HbA1c (WMD -0.06 %; 95 % CI -0.35, 0.23; I 2 = 42 %) vs. placebo. Finally, there was no effect on the incidence of severe hypoglycaemic events or overall serious adverse events [risk ratio 0.94, 95 % CI 0.62, 1.41; I 2 = 0 % and 0.87; 95 % CI 0.53, 1.44; I 2 = 0 %, respectively). Antigen-based immunotherapies are not effective in preventing the progression of autoimmune diabetes in newly diagnosed patients.

Improvement in glycemic control through changes in insulin regimens: findings from a Japanese cohort of children and adolescents with type 1 diabetes

Although insulin analogs have dramatically changed diabetes treatment, scarce evidence is available on those effects. We aimed to explore whether glycemic control had improved, the use of insulin analogs had been increased, and hypoglycemic events had decreased over time in Japanese pediatric patients with type 1 diabetes (T1D). Glycated hemoglobin A1c (HbA1c) values, proportion of insulin regimens, incidence of severe hypoglycemic events, and pubertal increase in HbA1c were compared in three cohorts of childhood-onset Japanese T1D patients (567 subjects in the 1995 cohort, 754 subjects in the 2000 cohort, and 806 subjects in the 2008 cohort). Mean HbA1c values tended to decrease [78.5 mmol/mol (9.33%) in the 1995 cohort, 68.2 mmol/mol (8.39%) in the 2000 cohort, and 61.2 mmol/mol (7.75%) in the 2008 cohort; P < .0001]. The proportion of patients who received basal-bolus treatment tended to increase with statistical significance, as did the proportion on insulin analogs. The incidence of severe hypoglycemic events (events/100 patients/y) had decreased (19.1 in the 2000 cohort and 8.7 in the 2008 cohort; P = .02). The pubertal increase in HbA1c tended to decrease [males, 12.0 mmol/mol (1.10%) in 1995, 9.4 mmol/mol (0.85%) in 2008, and 9.4 mmol/mol (0.86%) in 2008; P = .55; females, 14.0 mmol/mol (1.28%) in 1995, 10.3 mmol/mol (0.94%) in 2000, and 4.2 mmol/mol (0.38%) in 2008; P = .0003]. Glycemic control and incidence of severe hypoglycemic events were chronologically improved, especially in female adolescents.

Impact of insulin pump therapy on long-term glycemic control in a pediatric Spanish cohort

AimsTo evaluate the efficacy and safety of Continuous Subcutaneous Insulin Infusion (CSII) in a pediatric cohort and to determine if the ISPAD/IDF/ADA criteria for good metabolic control are achieved during long periods of time. MethodsRetrospective longitudinal study including ninety patients [10.5 (6.5–13.9) years of age, 58% males]. Age at debut, type 1 diabetes mellitus duration, pubertal stage, HbA1c, insulin dose, mean number of glycemic controls, number of basal rates, % basal/total insulin, severe hypoglycemia and diabetic ketoacidosis events were analyzed. Subgroup analysis based on age and pubertal stage was performed. ResultsHbA1c decreased from 6.9% [52mmol/mol] to 6.7% [50mmol/mol] after one year of CSII. Afterwards, it remained less than 7% during the follow-up period (median 3.5±1.8 years (range 1–8). Prior to CSII, 76% of the subjects met ISPAD/ADA criteria. One year after initiating CSII, 96% of children had HbA1c<7.5%. Improvement in glycohemoglobin levels was most prominent in those patients with the highest HbA1c initial levels. Total insulin dose decreased from 0.89 to 0.73 UI/kg/day (p<0.001). Proportion of basal/total insulin changed significantly (47 to 42% (p<0.05)). Number of fractions of the basal rate increased from 5.6±1.8 at one year of CSII to 6.7±2.1 five years later. Incidence of severe hypoglycemic events decreased from 19 to 6.9 episodes/100 patient-year. Only 2 episodes of diabetic ketoacidosis occurred. ConclusionsCSII allows reaching ISPAD/IDF/ADA goals safely during an extended follow-up period in a diabetic pediatric cohort.

Hypoglycaemia in sulphonylurea-treated subjects with type 2 diabetes undergoing Ramadan fasting: a five-country observational study

Objectives:To determine the incidence of hypoglycaemia during Ramadan in Muslim subjects with type 2 diabetes treated with a sulphonylurea.Methods:In an observational study, eligible subjects were Muslims with type 2 diabetes (age ≥18 years) who were treated with glimepiride, gliclazide, or glibenclamide with or without metformin and who expressed their intention to fast during Ramadan in 2009. Subjects were recruited by clinicians in India, Malaysia, Israel, the United Arab Emirates (UAE), and Saudi Arabia. Each day during Ramadan, patients completed diary cards, which collected information regarding hypoglycaemic symptoms and complications, time from last meal and from last medication, self-monitored blood glucose measurements, and need for assistance. The overall incidence of symptomatic hypoglycaemia recorded during Ramadan was the primary endpoint of interest.Results:Of the enrolled subjects (N = 1397), 1378 returned their diary cards at study end and were included in the analysis. Overall, 89% of subjects who expressed their intention to fast prior to Ramadan reported that they observed the fast during Ramadan. A total of 271 subjects (19.7%) experienced one or more symptomatic hypoglycaemic events during Ramadan, with incidences of 25.6%, 16.8%, and 14.0% observed in subjects treated with glibenclamide, glimepiride, and gliclazide, respectively. By country, the highest incidence of hypoglycaemia was reported by subjects from Israel (40%) followed by those from Malaysia (24%), the UAE (18%), India (13%), and Saudi Arabia (10%). The overall incidence of severe hypoglycaemic events (i.e., events requiring medical or non-medical assistance) was 6.7%, with the highest incidence occurring in the glibenclamide group.Limitations:This was an observational study and as such subjects were not randomised to treatments. While baseline measures appeared comparable, it is possible that differences in measured and unmeasured patient characteristics (e.g., measures of glycaemic control) could partially explain these results. Lastly, no inferential testing was performed on the comparisons between sulphonylurea types and/or countries.Conclusions:In this five-country observational study, nearly 20% of sulphonylurea-treated Muslim subjects with type 2 diabetes experienced symptomatic hypoglycaemia while fasting during Ramadan, with variations across sulphonylureas and countries.

Continuous Glucose Monitoring in Youth with Type 1 Diabetes: 12-Month Follow-Up of the Juvenile Diabetes Research Foundation Continuous Glucose Monitoring Randomized Trial

The use of continuous glucose monitoring (CGM) in the pediatric population is not well characterized. We have evaluated the use of CGM over a 12-month interval in youth with type 1 diabetes (TID) and have provided a description of CGM use. Eighty subjects 8-17 years old with T1D and baseline hemoglobin A1c (HbA1c) >or=7.0% used CGM as part of a 6-month randomized trial and subsequent 6-month extension study. Outcomes included frequency of CGM use, HbA1c levels, rate of severe hypoglycemia, and a CGM satisfaction scale. Seventy-six (95%) of 80 subjects were using CGM after 6 months (median use = 5.5 days/week) compared with 67 (84%) after 12 months (median use = 4.0 days/week). The 17 subjects using CGM >or=6 days/week in month 12 had substantially greater improvement from baseline in HbA1c than did the 63 subjects using CGM <6 days/week in month 12 (mean change - 0.8 +/- 0.6% vs. +0.1 +/- 0.7%, P < 0.001). They also reported greater satisfaction with use of CGM (P = 0.001). The incidence of severe hypoglycemic events was low during the 12 months of the study irrespective of the amount of CGM use. In youth with T1D, frequency of use decreases over time. Individuals who use CGM on a near-daily basis can have substantial improvement in glycemic control.

Latest news and product developments

Latest news and product developments

Two-Year Safety and Efficacy of Inhaled Human Insulin (Exubera) in Adult Patients With Type 1 Diabetes

The purpose of this study was to evaluate the long-term (2-year) safety and efficacy of inhaled human insulin (Exubera [insulin human (rDNA origin)] inhalation powder) (EXU) in adult patients with type 1 diabetes. Patients were randomly assigned to receive EXU (n = 290) or subcutaneous (s.c.) insulin (n = 290), plus basal (intermediate- or long-acting) insulin. The primary end point was the annual rate of decline in pulmonary function (forced expiratory volume in 1 s [FEV1] and carbon monoxide diffusing capacity [DL(CO)]). The mean +/- SEM annual rates of change between months 0 and 24 were -0.051 +/- 0.005 l/year with EXU and -0.034 +/- 0.005 l/year with s.c. insulin (significant mean difference -0.017 +/- 0.007 l/year [90% CI -0.028 to -0.005]) for FEV1 and -0.437 +/- 0.073 ml x min(-1) x mmHg(-1) x year(-1) with EXU and -0.287 +/- 0.065 ml x min(-1) x mmHg(-1) x year(-1) with s.c. insulin (nonsignificant mean difference -0.150 ml x min(-1) x mmHg(-1) x year(-1) [-0.310 to 0.011]) for DL(CO). The mean annual rates of change in FEV1 between months 3 and 24 were -0.041 +/- 0.005 and -0.031 +/- 0.006 l/year in the EXU and s.c. insulin groups, respectively (nonsignificant mean difference -0.011 l/year [-0.023 to 0.002]), indicating that the significant difference between the treatment groups in FEV1 developed during the first 3 months and was not progressive thereafter. Adverse event profiles were similar except for a higher incidence of cough (usually mild and unproductive) in patients receiving EXU (37.6 vs. 13.1%) that decreased to 1.3% by month 24. Glycemic control was sustained in both groups (adjusted mean treatment difference in change from baseline A1C at month 24 0.25 +/- 0.07% [0.13-0.37]). Although the overall hypoglycemic events were comparable between groups (4.0 vs. 3.8 events/subject-month), the incidence of severe hypoglycemic events was lower with EXU than with s.c. insulin (2.8 vs. 4.1 events/100 subject-months, risk ratio 0.67 [0.57-0.79]). Body weight increased to a significantly lesser extent with EXU (adjusted mean treatment difference -1.25 +/- 0.36 kg [-1.85 to -0.66]). Treatment group differences in lung function between EXU and s.c. insulin in adult patients with type 1 diabetes are small, develop early, and are nonprogressive for up to 2 years of therapy.