Impact of the Fasting Plasma Glucose Titration Target on the Success of Basal Insulin Titration in Insulin-Naïve Patients with Type 2 Diabetes: A Systematic Analysis.

"Conflicts of Interest MAN has been a member on advisory boards or has consulted with Boehringer Ingelheim, Eli Lilly & Co., Menarini/Berlin Chemie, Merck Sharp & Dohme, Novo Nordisk, Regor, and ShouTi and is a member of the data monitoring and safety board with Inventiva. He has received grant support from Eli Lilly & Co. and Merck Sharp & Dohme. He has also served on the speakers' bureau of AstraZeneca, Boehringer Ingelheim, Eli Lilly & Co., Menarini/Berlin Chemie, Medscape, Medical Learning Institute, Merck Sharp & Dohme, Novo Nordisk, and Sun Pharma. All the other authors declared that they have no conflicts of interest."

"For the present analysis, articles reporting prospective, randomized, blinded, or open-label clinical trials of initiating basal insulin treatment in insulin-naïve type 2 diabetic patients on a background of a well-defined therapy with single or combined oral glucose-lowering agents were identified through a systematic PubMed search. The search terms are displayed in Supplementary Table . We searched for prospective, randomized, clinical trials published between 1999 and October 2020 providing details on the basal insulin titration process like (a) insulin preparations used; (b) background oral glucose-lowering medications (at least by class); (c) person performing the titration; (d) initial insulin doses; (e) titration intervals (categorized as daily, every 3 days or twice a week, and weekly or in association with study visits (including telephone contacts) only) or the number of titration opportunities (multiplying the occasions per week with the total study duration); (f) “stringency” of the titration algorithm (steepness of the relationship between categories of hyperglycemia and the proposed increment in basal insulin dose); and (g) fasting plasma glucose titration targets. Additional inclusion criteria were (h) study duration ≥24 weeks, (i) a minimum number of 50 patients per study arm, and (k) report of essential information regarding baseline characteristics (age, sex, duration of diabetes, body weight and body mass index, fasting plasma glucose, and HbA1c) and relevant outcomes at the completion of the study (fasting plasma glucose, HbA1c, and HbA1c target achievement < 7.0% (<53.0 mmol/mol) and ≤6.5 (47.5 mmol/mol), insulin dose after titration (per day and/or per kg body weight and day), change in body weight, and the proportion of patients reporting any symptomatic or severe hypoglycemia. Exclusion criteria were publications reporting cross-over studies, concerning other types of diabetes, reporting results concerning specific ethnic groups other than Caucasian or internationally mixed populations only, studies allowing concomitant use of GLP-1 receptor agonists (exception: <5.0% of the study population as a consequence of protocol violations, overall), studies with >10% patients with preexisting basal insulin therapy, and studies reporting >5% of patients treated with rapid-acting insulin preparations as part of the rescue strategy. Of 1060 records identified initially, 43 publications representing 61 study arms could be used. Exclusion criteria are described in Supplementary Figure according to the PRISMA statement []. We registered our protocol with PROSPERO (https://www.crd.york.ac.uk/prospero/; identification no. CRD42019134821)."