Summary of findings 2. GLP‐1 analogues for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus.

GLP‐1 analogues for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus
Population: people at risk for development of T2DM Settings: outpatients Intervention: GLP‐1 analogues Comparison: placebo
Outcomes	Placebo	GLP‐1 analogues	Relative effect (95% CI)	No of participants (trial(s))	Quality of the evidence (GRADE)	Comments
All‐cause mortality Follow‐up: up to 172 weeks	See comment	See comment	See comment	2281 (2)	⊕⊝⊝⊝ Very lowa	1 trial reported that 2/1501 in the liraglutide group vs 2/747 in the placebo group died after 160 weeks of intervention. Liraglutide used in doses approved for weight‐reducing purposes (3.0 mg) (SCALE). 1 trial using exenatide reported that none of the participants died (Rosenstock 2010)
Incidence of T2DM Definition/description: 1 trial established the diagnosis of T2DM defined as HbA1c ≥ 6.5%, or fasting plasma glucose ≥ 7.0 mmol/L, or 2‐hour plasma glucose post‐challenge (oral glucose tolerance test) ≥ 11.1 mmol/L (SCALE). Other trial did not report how the diagnosis of T2DM was established. Follow‐up: up to 172 weeks	See comment	See comment	See comment	2243 (2)	⊕⊝⊝⊝ Very lowa	At 160 weeks, 26/1472 (1.8%) participants in the liraglutide group vs 46/738 (6.2%) participants in the placebo group developed T2DM (SCALE). The incidence of T2DM after the 12‐week off‐treatment extension period (i.e. after 172 weeks) showed that 5 additional participants were diagnosed with T2DM in the liraglutide group, compared with 1 participant in the placebo group. Liraglutide used in doses approved for weight‐reducing purposes (3.0 mg). 1 trial reported that 2/17 in the exenatide group vs1/16 in the placebo group developed T2DM (Rosenstock 2010)
Serious adverse events Follow‐up: up to 172 weeks	See comment	See comment	See comment	2312 (2)	⊕⊕⊝⊝ Lowb	1 trial on liraglutide reported that 227/1501 (15.1%) participants in the liraglutide 3.0 mg group vs 96/747 (12.7%) participants in the placebo group experienced a serious adverse event after 160 weeks (SCALE). 1 trial on exenatide reported that none of the participants experienced a serious adverse event (Rosenstock 2010)
Cardiovascular mortality Follow‐up: up to 172 weeks	See comment	See comment	See comment	2281 (2)	⊕⊝⊝⊝ Very lowa	1 trial reported that none of the participants died (Rosenstock 2010). 1 trial reported that 1/1501 participants in the liraglutide group died from cardiac arrest; no participant in the placebo group died of cardiovascular reasons (SCALE).
(1) Non‐fatal myocardial infarction (2) Non‐fatal stroke (3) Congestive heart failure Follow‐up: up to 172 weeks	See comment	See comment	See comment	(1) 2279 (1) (2) See comments (3) 2279 (1)	⊕⊝⊝⊝ Very lowa	(1) 1 trial reported 1/1524 participants in the liraglutide 3.0 mg group vs 0/755 participants in the placebo group (SCALE) (2) Not reported (3) 1 trial reported 1/1524 in the liraglutide 3.0 mg group vs 1/755 participants in the placebo group (SCALE)
Health‐related quality of life SF‐36 scale: total score 0‐100, 8 subscales. Higher values mean better health‐related quality of life. Follow‐up: 160 weeks	See comment	See comment	See comment	1791 (1)	⊕⊝⊝⊝ Very lowa	Physical functioning component score had mean difference of 0.87 in favour of liraglutide (SCALE)
Socioeconomic effects	See comment	See comment	See comment	See comment	See comment	Not reported
*The basis for the assumed risk (e.g. the median control group risk across trials) 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; GLP‐1: glucagon‐like peptide‐1; HbA1c: glycosylated haemoglobin A1c; RR: risk ratio; SF‐36: 36‐item Short Form health survey; T2DM: type 2 diabetes mellitus.
GRADE Working Group grades of evidence High quality: Further research is very unlikely to change our confidence in the estimate of effect. Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Very low quality: We are very uncertain about the estimate.

^aDowngraded by three levels because of indirectness, imprecision (sparse data) and risk of attrition and publication bias (see Appendix 16).
 ^bDowngraded by two levels because of imprecision (sparse data) and risk of attrition and publication bias (see Appendix 16).