TABLE 5.

Comparison of Safety Results in Randomized Trials Evaluating Co-Formulations of a Basal Insulin and a GLP-1 Receptor Agonist

DUAL I (34)DUAL IV (40)DUAL VI (41)LixiLan-O (37)
Hypoglycemia
Confirmed* (events/patient-year)IDegLira: 1.78 IDeg: 2.79 Lira: 0.19IDegLira: 3.52 Placebo: 1.35IDegLira 1WT: 0.16 IDegLira 2WT: 0.76iGlarLixi: 1.4 IGlar: 1.2 Lixi: 0.3
RR 0.63 (0.50–0.79) IDegLira vs. IDeg P <0.0001 RR 8.52 (6.09–11.93) IDegLira vs. Lira P <0.0001RR 3.74 (2.28–6.13) IDegLira vs. placebo P <0.001RR not calculatedTreatment contrast NR
Nocturnal (events/patient-year)IDegLira: 0.22 IDeg: 0.37 Lira: 0.018IDegLira: 0.49 Placebo: 0.32IDegLira 1WT: 0.02 IDegLira 2WT: 0.23NR
RR 0.68 (0.44–1.06) IDegLira vs. IDeg P =0.09 RR 11.99 (4.85–29.63) IDegLira vs. Lira P <0.0001RR 2.22 (0.99–5.00) IDegLira vs. placebo P =0.053RR not calculated
Severe (n)IDegLira: 3 IDeg: 2 Lira: 2IDegLira: 2 Placebo: 0IDegLira 1WT: 0 IDegLira 2WT: 1iGlarLixi: 0 IGlar: 1 Lixi: 0
Change in body weight (kg)IDegLira: –0.4 IDeg: +2.3 Lira: –3.0IDegLira: +0.5 Placebo: –1.0IDegLira 1WT: –1.0 IDegLira 2WT: –2.0iGlarLixi: –0.3 IGlar: +1.1 Lixi: –2.3
ETD –2.80 IDegLira vs. IDeg P <0.0001 ETD +2.66 IDegLira vs. Lira P <0.0001ETD +1.48 (0.90–2.06) IDegLira vs. placebo P <0.001ETD +1.09 (0.22–1.96) IDegLira 1WT vs. 2WT P = 0.014ETD –1.4 (–1.9 to –0.9) iGlarLixi vs. IGlar P <0.0001 ETD +2.0 (1.4–2.6) iGlarLixi vs. IGlar P <0.0001
Adverse events||
Nausea events (%)IDegLira: 9 IDeg: 4 Lira: 20 (51)IDegLira: 4.5 Placebo: 3.4IDegLira 1WT: 5.3 IDegLira 2WT: 5.2iGlarLixi: 9.6 IGlar: 3.6 Lixi: 24
Pancreatitis (n)IDegLira: 0 IDeg: 1 Lira: 2IDegLira: 0 Placebo: 0IDegLira 1WT: 0 IDegLira 2WT: 0iGlarLixi: 0 IGlar: 0 Lixi: 0
Change in lipase (u/L)IDegLira: +8.3 IDeg: –7.1 Lira: +12.5IDegLira: +6.7 Placebo: –2.0NRNumber of patients with lipase ≥3 × ULN: iGlarLixi: 4 IGlar: 6 Lixi: 5
Cardiovascular events (n)IDegLira: 8 IDeg: 8 Lira: 4IDegLira: 4 Placebo: 0IDegLira 1WT: 1 IDegLira 2WT: 1iGlarLixi: 2 IGlar: 7 Lixi: 2
Medullary thyroid carcinoma (n)NoneNoneNoneNot mentioned
  • Values are reported as mean (95% CI) except for ETDs in body weight in DUAL I, for which 95% CIs were not reported.

  • * Definitions and biochemical cut points varied across the trials. DUAL I and DUAL IV: confirmed hypoglycemia, SMBG value <56 mg/dL irrespective of symptoms; DUAL VI: confirmed symptomatic hypoglycemia, SMBG value <56 mg/dL with typical symptoms; LixiLan-O: documented symptomatic hypoglycemia, plasma glucose ≤70 mg/dL plus typical symptoms.

  • Nocturnal confirmed hypoglycemia, plasma glucose <56 mg/dL between 00:01 and 05:59 hours inclusive.

  • Severe defined as events requiring assistance.

  • || Adverse events confirmed by external adjudication committee.

  • Statistical analysis not performed as a result of the potential inherent bias of higher frequency of blood glucose measurements in the IDegLira 2WT group.

  • 1WT, once weekly titration; 2WT, twice weekly titration; IDeg, insulin degludec U100; IGlar, insulin glargine U100; Lira, liraglutide 6 mg/mL; NR, not reported; ULN, upper limit of normal.