Summary of findings 2. Summary of findings: insulin glargine versus NPH insulin.

Insulin glargine compared with NPH insulin for T1DM
Patients: people with T1DM Settings: outpatients Intervention: insulin glargine Comparison: NPH insulin
Outcomes	NPH insulin	Insulin glargine	Relative effect (95% CI)	No of participants (studies)	Certainty of the evidence (GRADE)	Comments
All‐cause mortality Follow‐up: 24‐52 weeks	See comment		Peto OR0.14 (0.00 to 6.98)	2175 (8)	⊕⊕⊕⊝ moderatea	1 study including adults reported 0/1207 participants died in the insulin glargine group vs 1/1068 participants in the NPH insulin group 4 studies included adults, 4 studies included children (the test for subgroup differences could not be performed)
Health‐related quality of life Scales: Well‐Being Enquiry for Diabetics; General Well‐being; Diabetes Quality of Life for Youth and Parents' Diabetes Quality of Life Follow‐up: 24‐28 weeks	See comment			1013 (4)	⊕⊕⊝⊝ lowb	1 study including adults (Bolli 2009) reported greater improvements in the insulin glargine group compared with NPH insulin in one domain (diabetes‐related worries) There was no evidence of a difference in 3 studies (Chase 2008 included children; Home 2005 and Ratner 2000 included adults)
Severe hypoglycaemia (n/N) Definition: symptomatic hypoglycaemia requiring third party assistance, with either a blood glucose level < 2.8 mmol/L or prompt recovery after administration of oral carbohydrate, iv glucose or glucagon (Fulcher 2005; Home 2005; Schober 2002); requiring third party assistance and associated with either blood glucose < 2.0 mmol/L or prompt recovery after oral carbohydrate, iv glucose, or intramuscular or subcutaneous glucagon administration (Chase 2008); hypoglycaemia requiring third party assistance or involving a seizure, coma, unconsciousness or the use of glucagon (Liu 2016); hypoglycaemia requiring third party assistance (Porcellati 2004; PRESCHOOL; Ratner 2000) Follow‐up: 24‐52 weeks	125 per 1000	105 per 1000 (84 to 130)	RR 0.84 (0.67 to 1.04)	2350 (9)	⊕⊕⊕⊝ moderatec	The 95% prediction interval ranged between 0.65 and 1.09 5 studies included adults, 4 studies included children (the test for subgroup differences did not indicate interaction)
Non‐fatal myocardial infarction/stroke Definition: myocardial infarction/cerebral ischaemia Follow‐up: 28 weeks	See comment			585 (1)	⊕⊕⊝⊝ lowd	No participant experienced a non‐fatal myocardial infarction 1 study including adults reported 0/292 participants in the insulin glargine group vs 1/293 participants in the NPH insulin group experienced cerebral ischaemia (Home 2005)
Severe nocturnal hypoglycaemia (n/N) Definition: severe hypoglycaemia occurring 23:00‐07:00 (PRESCHOOL); severe hypoglycaemia occurring after the evening insulin injection and before the morning insulin dose (Fulcher 2005); severe hypoglycaemia occurring during sleep between bedtime and rising in the morning, or before the morning pre‐breakfast self‐blood glucose measurement and the morning insulin injection (Home 2005); severe hypoglycaemia occurring while asleep after the bedtime insulin dose and before the morning insulin dose and before the morning blood glucose measurement (Ratner 2000); severe hypoglycaemia while the participant was sleeping between bedtime and after the evening injection and before getting up in the morning (Schober 2002); severe hypoglycaemia occurring 00:00‐06:00 (Chase 2008) Follow‐up: 24‐28 weeks	87 per 1000	72 per 1000 (54 to 97)	RR 0.83 (0.62 to 1.12)	1893 (6)	⊕⊕⊕⊝ moderatec	The 95% prediction interval ranged between 0.54 and 1.27 3 studies included adults, 3 studies included children (the test for subgroup differences did not indicate interaction)
Serious adverse events (n/N) Follow‐up: 24‐30 weeks	100 per 1000	108 per 1000 (63 to 184)	RR 1.08 (0.63 to 1.84)	2229 (8)	⊕⊕⊕⊝ moderatec	The 95% prediction interval ranged between 0.22 and 5.21 4 studies included adults, 4 studies included children (the test for subgroup differences did not indicate interaction)
HbA1c (%) Follow‐up: 24 weeks ‐ 1 year	The mean HbA1c ranged across the NPH insulin groups from 7.1% to 7.3%	The mean HbA1c in the insulin glargine groups was 0.02% higher (0.1% lower to 0.1% higher)	—	2285 (9)	⊕⊕⊕⊝ moderatec	The 95% prediction interval ranged between ‐0.5% and 0.5% 5 studies included adults, 4 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). a.m.: ante meridiem; CI: confidence interval; HbA1c: glycosylated haemoglobin A1c; iv: intravenous; n/N: number of people experiencing an event; NPH: neutral protamine Hagedorn; 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 2.
^bDowngraded by two levels because of overall risk of bias ('some concerns') and imprecision (few studies) ‐ see Appendix 2.
^cDowngraded by one level because of imprecision (CI consistent with benefit and harm) ‐ see Appendix 2.
^dDowngraded by two levels because of indirectness (insufficient time frame) and imprecision (few studies) ‐ see Appendix 2.