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].