Effect of Insulin Degludec vs Insulin Glargine U100 on Hypoglycemia in Patients With Type 1 Diabetes The SWITCH 1 Randomized Clinical Trial

Question  Is the rate of hypoglycemia noninferior or lower with insulin degludec vs insulin glargine U100 in insulin-treated patients with type 1 diabetes?

Findings  In this randomized crossover trial of 501 patients, insulin degludec compared with insulin glargine U100 resulted in a significantly lower rate of overall symptomatic hypoglycemic episodes over a 16-week maintenance period (2201 vs 2463 episodes per 100 patient-years of exposure).

Meaning  Patients with type 1 diabetes treated with insulin degludec, compared with insulin glargine U100, had a reduced risk of overall symptomatic hypoglycemia.

Reference: JAMA. 2017;318(1):33-44.

Advertisements

Incidence Trends of Type 1 and Type 2 Diabetes among Youths, 2002–2012

BACKGROUND

Diagnoses of type 1 and type 2 diabetes in youths present a substantial clinical and public health burden. The prevalence of these diseases increased in the 2001–2009 period, but data on recent incidence trends are lacking.

METHODS

We ascertained cases of type 1 and type 2 diabetes mellitus at five study centers in the United States. Denominators (4.9 million youths annually) were obtained from the U.S. Census or health-plan member counts. After the calculation of annual incidence rates for the 2002–2012 period, we analyzed trends using generalized autoregressive moving-average models with 2-year moving averages.

RESULTS

A total of 11,245 youths with type 1 diabetes (0 to 19 years of age) and 2846 with type 2 diabetes (10 to 19 years of age) were identified. Overall unadjusted estimated incidence rates of type 1 diabetes increased by 1.4% annually (from 19.5 cases per 100,000 youths per year in 2002–2003 to 21.7 cases per 100,000 youths per year in 2011–2012, P=0.03). In adjusted pairwise comparisons, the annual rate of increase was greater among Hispanics than among non-Hispanic whites (4.2% vs. 1.2%, P<0.001). Overall unadjusted incidence rates of type 2 diabetes increased by 7.1% annually (from 9.0 cases per 100,000 youths per year in 2002–2003 to 12.5 cases per 100,000 youths per year in 2011–2012, P<0.001 for trend across race or ethnic group, sex, and age subgroups). Adjusted pairwise comparisons showed that the relative annual increase in the incidence of type 2 diabetes among non-Hispanic whites (0.6%) was lower than that among non-Hispanic blacks, Asians or Pacific Islanders, and Native Americans (P<0.05 for all comparisons) and that the annual rate of increase among Hispanics differed significantly from that among Native Americans (3.1% vs. 8.9%, P=0.01). After adjustment for age, sex, and race or ethnic group, the relative annual increase in the incidence of type 1 diabetes was 1.8% (P<0.001) and that of type 2 diabetes was 4.8% (P<0.001).

CONCLUSIONS

The incidences of both type 1 and type 2 diabetes among youths increased significantly in the 2002–2012 period, particularly among youths of minority racial and ethnic groups. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Centers for Disease Control and Prevention.)

N Engl J Med 2017; 376:1419-1429

Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes

BACKGROUND

Long-term trends in excess risk of death and cardiovascular outcomes have not been extensively studied in persons with type 1 diabetes or type 2 diabetes.

METHODS

We included patients registered in the Swedish National Diabetes Register from 1998 through 2012 and followed them through 2014. Trends in deaths and cardiovascular events were estimated with Cox regression and standardized incidence rates. For each patient, controls who were matched for age, sex, and county were randomly selected from the general population.

RESULTS

Among patients with type 1 diabetes, absolute changes during the study period in the incidence rates of sentinel outcomes per 10,000 person-years were as follows: death from any cause, −31.4 (95% confidence interval [CI], −56.1 to −6.7); death from cardiovascular disease, −26.0 (95% CI, −42.6 to −9.4); death from coronary heart disease, −21.7 (95% CI, −37.1 to −6.4); and hospitalization for cardiovascular disease, −45.7 (95% CI, −71.4 to −20.1). Absolute changes per 10,000 person-years among patients with type 2 diabetes were as follows: death from any cause, −69.6 (95% CI, −95.9 to −43.2); death from cardiovascular disease, −110.0 (95% CI, −128.9 to −91.1); death from coronary heart disease, −91.9 (95% CI, −108.9 to −75.0); and hospitalization for cardiovascular disease, −203.6 (95% CI, −230.9 to −176.3). Patients with type 1 diabetes had roughly 40% greater reduction in cardiovascular outcomes than controls, and patients with type 2 diabetes had roughly 20% greater reduction than controls. Reductions in fatal outcomes were similar in patients with type 1 diabetes and controls, whereas patients with type 2 diabetes had smaller reductions in fatal outcomes than controls.

CONCLUSIONS

In Sweden from 1998 through 2014, mortality and the incidence of cardiovascular outcomes declined substantially among persons with diabetes, although fatal outcomes declined less among those with type 2 diabetes than among controls. (Funded by the Swedish Association of Local Authorities and Regions and others.)

Relative effectiveness of insulin pump treatment over multiple daily injections and structured education during flexible intensive insulin treatment for type 1 diabetes: cluster randomised trial (REPOSE)

Objective To compare the effectiveness of insulin pumps with multiple daily injections for adults with type 1 diabetes, with both groups receiving equivalent training in flexible insulin treatment.

Design Pragmatic, multicentre, open label, parallel group, cluster randomised controlled trial (Relative Effectiveness of Pumps Over MDI and Structured Education (REPOSE) trial).

Setting Eight secondary care centres in England and Scotland.

Participants Adults with type 1 diabetes who were willing to undertake intensive insulin treatment, with no preference for pumps or multiple daily injections. Participants were allocated a place on established group training courses that taught flexible intensive insulin treatment (“dose adjustment for normal eating,” DAFNE). The course groups (the clusters) were then randomly allocated in pairs to either pump or multiple daily injections.

Interventions Participants attended training in flexible insulin treatment (using insulin analogues) structured around the use of pump or injections, followed for two years.

Main outcome measures The primary outcomes were a change in glycated haemoglobin (HbA1c) values (%) at two years in participants with baseline HbA1c value of ≥7.5% (58 mmol/mol), and the proportion of participants achieving an HbA1c value of <7.5%. Secondary outcomes included body weight, insulin dose, and episodes of moderate and severe hypoglycaemia. Ancillary outcomes included quality of life and treatment satisfaction.

Results 317 participants (46 courses) were randomised (156 pump and 161 injections). 267 attended courses and 260 were included in the intention to treat analysis, of which 235 (119 pump and 116 injection) had baseline HbA1c values of ≥7.5%. Glycaemic control and rates of severe hypoglycaemia improved in both groups. The mean change in HbA1c at two years was −0.85% with pump treatment and −0.42% with multiple daily injections. Adjusting for course, centre, age, sex, and accounting for missing values, the difference was −0.24% (−2.7 mmol/mol) in favour of pump users (95% confidence interval −0.53 to 0.05, P=0.10). Most psychosocial measures showed no difference, but pump users showed greater improvement in treatment satisfaction and some quality of life domains (dietary freedom and daily hassle) at 12 and 24 months.

Conclusions Both groups showed clinically relevant and long lasting decreases in HbA1c, rates of severe hypoglycaemia, and improved psychological measures, although few participants achieved glucose levels currently recommended by national and international guidelines. Adding pump treatment to structured training in flexible intensive insulin treatment did not substantially enhance educational benefits on glycaemic control, hypoglycaemia, or psychosocial outcomes in adults with type 1 diabetes. These results do not support a policy of providing insulin pumps to adults with poor glycaemic control until the effects of training on participants’ level of engagement in intensive self management have been determined.

Trial registration Current Controlled Trials ISRCTN61215213.

BMJ 2017;356:j1285

Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial

Background

The safety and effectiveness of a continuous, day-and-night automated glycaemic control system using insulin and glucagon has not been shown in a free-living, home-use setting. We aimed to assess whether bihormonal bionic pancreas initialised only with body mass can safely reduce mean glycaemia and hypoglycaemia in adults with type 1 diabetes who were living at home and participating in their normal daily routines without restrictions on diet or physical activity.

Methods

We did a random-order crossover study in volunteers at least 18 years old who had type 1 diabetes and lived within a 30 min drive of four sites in the USA. Participants were randomly assigned (1:1) in blocks of two using sequentially numbered sealed envelopes to glycaemic regulation with a bihormonal bionic pancreas or usual care (conventional or sensor-augmented insulin pump therapy) first, followed by the opposite intervention. Both study periods were 11 days in length, during which time participants continued all normal activities, including athletics and driving. The bionic pancreas was initialised with only the participant’s body mass. Autonomously adaptive dosing algorithms used data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon. The coprimary outcomes were the mean glucose concentration and time with continuous glucose monitoring (CGM) glucose concentration less than 3·3 mmol/L, analysed over days 2–11 in participants who completed both periods of the study. This trial is registered with ClinicalTrials.gov, number NCT02092220.

Findings

We randomly assigned 43 participants between May 6, 2014, and July 3, 2015, 39 of whom completed the study: 20 who were assigned to bionic pancreas first and 19 who were assigned to the comparator first. The mean CGM glucose concentration was 7·8 mmol/L (SD 0·6) in the bionic pancreas period versus 9·0 mmol/L (1·6) in the comparator period (difference 1·1 mmol/L, 95% CI 0·7–1·6; p<0·0001), and the mean time with CGM glucose concentration less than 3·3 mmol/L was 0·6% (0·6) in the bionic pancreas period versus 1·9% (1·7) in the comparator period (difference 1·3%, 95% CI 0·8–1·8; p<0·0001). The mean nausea score on the Visual Analogue Scale (score 0–10) was greater during the bionic pancreas period (0·52 [SD 0·83]) than in the comparator period (0·05 [0·17]; difference 0·47, 95% CI 0·21–0·73; p=0·0024). Body mass and laboratory parameters did not differ between periods. There were no serious or unexpected adverse events in the bionic pancreas period of the study.

Interpretation

Relative to conventional and sensor-augmented insulin pump therapy, the bihormonal bionic pancreas, initialised only with participant weight, was able to achieve superior glycaemic regulation without the need for carbohydrate counting. Larger and longer studies are needed to establish the long-term benefits and risks of automated glycaemic management with a bihormonal bionic pancreas.

Funding

National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and National Center for Advancing Translational Sciences.

The Lancet, Volume 389, No. 10067, p369–380, 28 January 2017

Continuous Glucose Monitoring vs Conventional Therapy for Glycemic Control in Adults With Type 1 Diabetes Treated With Multiple Daily Insulin Injections The GOLD Randomized Clinical Trial

Key Points

Question  Does continuous glucose monitoring improve glycemic control in adults with type 1 diabetes treated with multiple daily insulin injections?

Findings  In this randomized clinical trial of 161 adults with type 1 diabetes, glycemic control was improved during continuous glucose monitoring compared with conventional treatment (hemoglobin [HbA1c] of 7.92% vs 8.35% [63 vs 68 mmol/mol]). The mean difference in HbA1c was 0.43% (4.7 mmol/mol).

Meaning  Continuous glucose monitoring may result in better glycemic control compared with conventional treatment, but further research is needed to assess clinical outcomes and longer-term adverse effects.

Abstract

Importance  The majority of individuals with type 1 diabetes do not meet recommended glycemic targets.

Objective  To evaluate the effects of continuous glucose monitoring in adults with type 1 diabetes treated with multiple daily insulin injections.

Design, Setting, and Participants  Open-label crossover randomized clinical trial conducted in 15 diabetes outpatient clinics in Sweden between February 24, 2014, and June 1, 2016 that included 161 individuals with type 1 diabetes and hemoglobin A1c (HbA1c) of at least 7.5% (58 mmol/mol) treated with multiple daily insulin injections.

Interventions  Participants were randomized to receive treatment using a continuous glucose monitoring system or conventional treatment for 26 weeks, separated by a washout period of 17 weeks.

Main Outcomes and Measures  Difference in HbA1c between weeks 26 and 69 for the 2 treatments. Adverse events including severe hypoglycemia were also studied.

Results  Among 161 randomized participants, mean age was 43.7 years, 45.3% were women, and mean HbA1c was 8.6% (70 mmol/mol). A total of 142 participants had follow-up data in both treatment periods. Mean HbA1c was 7.92% (63 mmol/mol) during continuous glucose monitoring use and 8.35% (68 mmol/mol) during conventional treatment (mean difference, −0.43% [95% CI, −0.57% to −0.29%] or −4.7 [−6.3 to −3.1 mmol/mol]; P < .001). Of 19 secondary end points comprising psychosocial and various glycemic measures, 6 met the hierarchical testing criteria of statistical significance, favoring continuous glucose monitoring compared with conventional treatment. Five patients in the conventional treatment group and 1 patient in the continuous glucose monitoring group had severe hypoglycemia. During washout when patients used conventional therapy, 7 patients had severe hypoglycemia.

Conclusions and Relevance  Among patients with inadequately controlled type 1 diabetes treated with multiple daily insulin injections, the use of continuous glucose monitoring compared with conventional treatment for 26 weeks resulted in lower HbA1c. Further research is needed to assess clinical outcomes and longer-term adverse effects.

Trial Registration  clinicaltrials.gov Identifier: NCT02092051

JAMA. 2017;317(4):379-387.

Effect of Continuous Glucose Monitoring on Glycemic Control in Adults With Type 1 Diabetes Using Insulin Injections The DIAMOND Randomized Clinical Trial

Key Points

Question  For adults with type 1 diabetes who are using multiple daily insulin injections, does continuous glucose monitoring improve hemoglobin A1c (HbA1c) levels compared with self-monitored blood glucose management?

Findings  In a randomized clinical trial of 158 adults with type 1 diabetes, there was a significantly greater decrease in HbA1c level during 24 weeks with continuous glucose monitoring vs usual care (–1.0% vs –0.4%).

Meaning  Continuous glucose monitoring resulted in better glycemic control compared with usual care, but further research is needed to assess clinical outcomes, as well as effectiveness, in a typical clinical population.

Abstract

Importance  Previous clinical trials showing the benefit of continuous glucose monitoring (CGM) in the management of type 1 diabetes predominantly have included adults using insulin pumps, even though the majority of adults with type 1 diabetes administer insulin by injection.

Objective  To determine the effectiveness of CGM in adults with type 1 diabetes treated with insulin injections.

Design, Setting, and Participants  Randomized clinical trial conducted between October 2014 and May 2016 at 24 endocrinology practices in the United States that included 158 adults with type 1 diabetes who were using multiple daily insulin injections and had hemoglobin A1c (HbA1c) levels of 7.5% to 9.9%.

Interventions  Random assignment 2:1 to CGM (n = 105) or usual care (control group; n = 53).

Main Outcomes and Measures  Primary outcome measure was the difference in change in central-laboratory–measured HbA1c level from baseline to 24 weeks. There were 18 secondary or exploratory end points, of which 15 are reported in this article, including duration of hypoglycemia at less than 70 mg/dL, measured with CGM for 7 days at 12 and 24 weeks.

Results  Among the 158 randomized participants (mean age, 48 years [SD, 13]; 44% women; mean baseline HbA1c level, 8.6% [SD, 0.6%]; and median diabetes duration, 19 years [interquartile range, 10-31 years]), 155 (98%) completed the study. In the CGM group, 93% used CGM 6 d/wk or more in month 6. Mean HbA1creduction from baseline was 1.1% at 12 weeks and 1.0% at 24 weeks in the CGM group and 0.5% and 0.4%, respectively, in the control group (repeated-measures model P < .001). At 24 weeks, the adjusted treatment-group difference in mean change in HbA1c level from baseline was –0.6% (95% CI, –0.8% to –0.3%; P < .001). Median duration of hypoglycemia at less than <70 mg/dL was 43 min/d (IQR, 27-69) in the CGM group vs 80 min/d (IQR, 36-111) in the control group (P = .002). Severe hypoglycemia events occurred in 2 participants in each group.

Conclusions and Relevance  Among adults with type 1 diabetes who used multiple daily insulin injections, the use of CGM compared with usual care resulted in a greater decrease in HbA1c level during 24 weeks. Further research is needed to assess longer-term effectiveness, as well as clinical outcomes and adverse effects.

Trial Registration  clinicaltrials.gov Identifier: NCT02282397