Efficacy and safety among second-generation and other basal insulins in adult patients with type 1 diabetes: a systematic review and network meta-analysis

We aimed to assess the comparative efficacy and safety of second-generation basal insulins (glargine U300 and degludec U100) vs. neutral protamine Hagedorn (NPH) and first-generation basal insulins (glargine U100 and detemir) in type 1 diabetes (T1D) adults. PubMed, the Cochrane Library, ClinicalTrials.gov, and Google Scholar (until January 2021) were systematically searched. Randomized controlled trials (RCTs) with >= 12 weeks of follow-up comparing efficacy (HbA(1c)) or safety (hypoglycemia and weight gain) between second-generation basal insulins vs. other basal insulins in T1D adults were included. Bayesian network meta-analyses were used to estimate risk ratio, hazard ratio, and mean difference. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to appraise evidence certainty. Eighteen RCTs (>= 24 weeks of follow-up) involving 7283 randomized participants were included for main analysis. Moderate to high certainty evidence suggested that second-generation basal insulins showed equivalent HbA(1c) reduction compared with NPH and first-generation basal insulins. Compared with second-generation basal insulins, low to high certainty evidence suggested that NPH was associated with a higher risk of patients experiencing severe hypoglycemia; NPH and first-generation basal insulins were associated with a higher rate of nocturnal confirmed hypoglycemic events. For the weight gain, glargine U300 was comparable to detemir (low certainty), but degludec U100 was greater than detemir (moderate certainty). In conclusion, second-generation basal insulins maintained equivalent efficacy of glycemic control (moderate to high certainty), with differences in safety (low to high certainty) compared with NPH and first-generation basal insulins during >= 24 weeks of follow-up in T1D adults.