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Cochrane Database of Systematic Reviews

(Ultra-)long-acting insulin analogues for people with type 1 diabetes mellitus

Overview of attention for article published in Cochrane database of systematic reviews, March 2021
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (92nd percentile)
  • Good Attention Score compared to outputs of the same age and source (70th percentile)

Mentioned by

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45 tweeters

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45 Mendeley
Title
(Ultra-)long-acting insulin analogues for people with type 1 diabetes mellitus
Published in
Cochrane database of systematic reviews, March 2021
DOI 10.1002/14651858.cd013498.pub2
Pubmed ID
Authors

Bianca Hemmingsen, Maria-Inti Metzendorf, Bernd Richter

Abstract

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.

Twitter Demographics

The data shown below were collected from the profiles of 45 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 45 100%

Demographic breakdown

Readers by professional status Count As %
Student > Master 8 18%
Researcher 6 13%
Student > Bachelor 4 9%
Librarian 2 4%
Student > Postgraduate 2 4%
Other 3 7%
Unknown 20 44%
Readers by discipline Count As %
Medicine and Dentistry 11 24%
Agricultural and Biological Sciences 3 7%
Nursing and Health Professions 2 4%
Pharmacology, Toxicology and Pharmaceutical Science 2 4%
Economics, Econometrics and Finance 1 2%
Other 5 11%
Unknown 21 47%

Attention Score in Context

This research output has an Altmetric Attention Score of 35. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 31 August 2021.
All research outputs
#769,972
of 18,829,177 outputs
Outputs from Cochrane database of systematic reviews
#1,867
of 11,869 outputs
Outputs of similar age
#21,809
of 309,984 outputs
Outputs of similar age from Cochrane database of systematic reviews
#13
of 40 outputs
Altmetric has tracked 18,829,177 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 11,869 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 26.6. This one has done well, scoring higher than 84% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 309,984 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 92% of its contemporaries.
We're also able to compare this research output to 40 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 70% of its contemporaries.