Summary of findings 1. Summary of findings: insulin detemir versus NPH insulin.

Insulin detemir compared with NPH insulin for T1DM
Patients: people with T1DM Settings: outpatients Intervention: insulin detemir Comparison: NPH insulin
Outcomes	NPH insulin	Insulin detemir	Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
All‐cause mortality Follow‐up: 24‐104 weeks	See comment		Peto OR4.97 (0.79 to 31.38)	3334 (9)	⊕⊕⊕⊝ moderatea	All 5 deaths reported in 2 studies including adults occurred in the insulin detemir group
Health‐related quality of life Description: diabetes health profile; insulin therapy‐related quality of life at night (scale not specified) Follow‐up: 26‐48 weeks	See comment			870 (3)	⊕⊕⊝⊝ lowb	No study reported health‐related quality of life in a format making it suitable for meta‐analysis 1 study including adults reported higher scores in the insulin detemir group vs the NPH insulin group (Kobayashi 2007) 2 studies did not show evidence of a difference between intervention groups (NCT00595374 included children; Standl 2004 included adults)
Severe hypoglycaemia (n/N) Definition: hypoglycaemia requiring third party assistance (Bartley 2008; Kobayashi 2007; NCT00605137; Robertson 2007; Russell‐Jones 2004; Standl 2004; Thalange 2013; Vague 2003); episodes where the children were semi‐conscious, unconscious or in a coma, with or without convulsions (Thalange 2013) Follow‐up: 24‐104 weeks	115 per 1000	79 per 1000 (60 to 106)	RR 0.69 (0.52 to 0.92)	3219 (8)	⊕⊕⊕⊝ moderatec	The 95% prediction interval ranged between 0.34 and 1.39 5 studies included adults, 3 studies included children (the test for subgroup differences did not indicate interaction)
Non‐fatal myocardial infarction/stroke Definition: myocardial infarction Follow‐up: 24 months	See comment			495 (1)	⊕⊕⊝⊝ lowd	1/331 participants in the insulin detemir group vs 0/164 participants in the NPH insulin group experienced a non‐fatal myocardial infarction (Bartley 2008) Stroke was not reported Study included adults
Severe nocturnal hypoglycaemia (n/N) Definition: severe hypoglycaemia occurring 23:00‐06:00 (Bartley 2008; NCT00605137; Russell‐Jones 2004; Standl 2004; Vague 2003); occurring 22:00‐07:00 (Robertson 2007; Thalange 2013) Follow‐up: 24 weeks ‐ 24 months	54 per 1000	36 per 1000 (21 to 64)	RR 0.67 (0.39 to 1.17)	2925 (7)	⊕⊕⊕⊝ moderatee	The 95% prediction interval ranged between 0.16 and 2.87 4 studies included adults, 3 studies included children (the test for subgroup differences did not indicate interaction)
Serious adverse events (n/N) Follow‐up: 24‐104 weeks	82 per 1000	78 per 1000 (62 to 100)	RR 0.95 (0.75 to 1.21)	3332 (9)	⊕⊕⊕⊝ moderatee	The 95% prediction interval ranged between 0.71 and 1.27 6 studies included adults, 3 studies included children (the test for subgroup differences did not indicate interaction)
HbA1c (%) Follow‐up: 24 weeks ‐ 24 months	The mean HbA1c ranged across the NPH insulin groups from 7.3% to 8.6%	The mean HbA1c in the insulin detemir groups was 0.01% higher (0.1% lower to 0.1% higher)	—	3122 (8)	⊕⊕⊕⊝ moderatee	The 95% prediction interval ranged between ‐0.1% and 0.1% 5 studies included adults, 3 studies included children (the test for subgroup differences did not indicate interaction)
*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; CSR: clinical study report; HbA1c: glycosylated haemoglobin A1c; n/N: number of people experiencing an event; NPH: neutral protamine Hagedorn; OR: odds ratio RR: risk ratio; T1DM: type 1 diabetes mellitus.
GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.

^*Assumed risk was derived from the event rates in the comparator groups.

^aDowngraded by one level because of indirectness (insufficient time frame) ‐ see Appendix 1.
^bDowngraded by two levels because of overall risk of bias ('some concerns') and imprecision (few studies) ‐ see Appendix 1.
^cDowngraded by one level because of inconsistency (95% prediction interval consistent with benefit and harm) ‐ see Appendix 1.
^dDowngraded by two levels because of indirectness (insufficient time frame) and imprecision (few studies) ‐ see Appendix 1.
^eDowngraded by one level because of imprecision (CI consistent with benefit and harm) ‐ see Appendix 1.