Study Investigational vs. comparator Population n Hypoglycemia category Result RRa/b (95% CI) P value BEGIN Once Long [46] Insulindegludec vs insulinglargine Adults with T2DM (A1C 7.0–10.0%) taking OADs only 1030 - Confirmed hypoglycemia (PG 54 mg/dl or severe*) - Nocturnal confirmed hypoglycemia - Severe* 1.52 vs 1.85 episodes/PYE 0.25 vs 0.39 episodes/PYE 0.003 vs 0.023 episodes/PYE RRa0.82 (0.64–1.04) RRa0.64 (0.42–0.98) RRa0.14 (0.03–0.70) 0.106 0.038 0.017 BEGIN Once Asia [49] Insulindegludec vs insulinglargine Asian adults with T2DM (A1C 7.0–10.0%) taking OADs only 435 - Confirmed hypoglycemia (PG <54 mg/dl or severe*) - Nocturnal confirmed hypoglycemia - Severe* 3.0 vs 3.7 episodes/PYE 0.8 vs 1.2 episodes/PYE - RRa0.82 (0.60–1.11) RRa0.62 (0.38–1.04) - 0.20 0.07 - BEGIN Basal-Bolus [47] Insulindegludec + insulinaspart vs insulindegludec + insulinaspart Adults with T2DM (A1C 7.0–10.0%) on any insulin regimen with or without OADs 1006 - Confirmed hypoglycemia (PG <54 mg/dl or severe*) - Nocturnal confirmed hypoglycemia - Severe* 11.1 vs 13.6 episodes/PYE 1.39 vs 1.84 episodes/PYE 0.06 vs 0.05 episodes/PYE RRa0.82 (0.69–0.99) RRa0.75 (0.58–0.99) - 0.0359 0.0399 - BEGIN Flex [48] Insulin degludec flexible† vs insulin degludec fixed vs insulin glargine Adults with T2DM taking OADs (A1C 7.0–11.0%) or basal insulin + OADs (A1C 7.0–10.0%) 687 - Confirmed hypoglycemia (PG 54 mg/dl or severe*) - Nocturnal confirmed hypoglycemia   - Severe* 3.6 vs 3.6 vs 3.5 episodes/PYE 0.6 vs 0.6 vs 0.8 episodes/PYE   - RRa1.03 (0.75–1.40) flexible vsglargine RRa1.10 (0.79–1.52) flexible vs fixed RRa0.77 (0.44–1.35) flexible vsglargine RRa1.18 (0.66–2.12) flexible vs fixed - NS NS NS NS - EDITION 1 [54] Insulinglargine U300 vs insulinglargine U100 Adults with T2DM (A1C 7.0–10.0%) using  ≥42 U/day basal insulin + mealtime insulin 807 - Confirmed hypoglycemia (PG ≤70 mg/dl or severe*) - Nocturnal confirmed hypoglycemia - Severe* 81.9% vs 87.8% 44.6% vs 57.5% 5.0% vs 5.7% RRb0.93 (0.88–0.99) RRb0.78 (0.68–0.89) RRb0.87 (0.48–1.55) - - - EDITION 2 [55] Insulinglargine U300 vs insulinglargine U100 Adults with T2DM (A1C 7.0–10.0%) using ≥42 U/day basal insulin + OADs 811 - Confirmed hypoglycemia (PG ≤70 mg/dl or severe*) - Nocturnal confirmed hypoglycemia - Severe* 70.0% vs 77.3% 28.3% vs39.9% 1.0% vs 1.5% RRb0.90 (0.83–0.98) RRb0.71 (0.58–0.86) - - - - EDITION 3 [56] Insulinglargine U300 vs insulinglargine U100 Adults with T2DM (A1C 7.0–11.0%) on OADs 878 - Confirmed hypoglycemia (PG ≤70 mg/dl or severe*) - Nocturnal confirmed hypoglycemia - Severe* 46.2% vs 52.5% 17.9% vs 23.5% 0.9% vs 0.9% RRb 0.88 (0.77–1.01) RRb 0.76 (0.59­–0.99) - - - - EDITION JP 2 [57] Insulinglargine U300 vs insulinglargine U100 Adults Asians with T2DM basal insulin + OADs 241 - Confirmed hypoglycemia (PG ≤70 mg/dl or severe*) - Nocturnal confirmed hypoglycemia - Severe* 65.0% vs 76.7% 28.3% vs 45.8% - RRb 0.86 (0.73–1.01) RRb 0.62 (0.44­–0.88) - - - - Bergenstal et al., 2012 [58] peglisprovs insulin glargine Adults with T2DM (A1C ≤10.5%) on basal insulin and OADs 289 - Total hypoglycemia (BG ≤70 mg/dl or symptoms) - Nocturnal hypoglycemia 1.34 vs 0.34 events/30 days 0.25 vs 0.39 events/30 days - - 0.804 0.178 ELEMENT 2 [61] LY2963016 vs insulin glargine Adults with T2DM on OADS (A1C 7.0–11.0%) or insulin glargine + OADs (A1C ≤11.0%) 756 - Total hypoglycemia (BG ≤70 mg/dl or symptoms) 21.3 vs 22.3 - 0.995 *requiring assistance; †dosing schedule creating 8-40hours between injections. A1C, glycated hemoglobin; BG, blood glucose; CI, confidence interval; NS, not significant; PG, plasma glucose; PYE, patient year of exposure; OADs, oral antidiabetic drugs; RRa, rate ratio; RRb, relative risk; T2DM, type 2 diabetes mellitus.

Table 1: Hypoglycemia in randomized clinical trials of novel basal analog insulins in T2DM [46-49,54-58,61].