Efficacy and Safety of Liraglutide 3.0 mg in Individuals With Overweight or Obesity and Type 2 Diabetes Treated With Basal Insulin: The SCALE Insulin Randomized Controlled Trial
Article Figures & Tables
Figures
- Figure 1
Change in body weight and glycemic control over time. A: Change in body weight (percentage); observed mean data ± SEM. n values refer to all individuals who attended visit regardless of treatment status; on-drug n values refer to individuals who were still on active treatment at time of visit. B: Change in HbA1c; observed mean data ± SEM. n values refer to all individuals who attended visit regardless of treatment status; on-drug n values refer to individuals who were still on active treatment at time of visit. C: Change in total daily insulin dose; graph shows observed mean data ± SEM. n values refer to all individuals who attended visit regardless of treatment status; on-drug n values refer to individuals who were still on active treatment at time of visit. U, units.
Tables
- Table 1
Baseline demographics and medications
Liraglutide 3.0 mg (n = 198) Placebo (n = 198) Male sex, n (%) 90 (45.5) 99 (50.0) Mean age, years (SD) 55.9 (11.3) 57.6 (10.4) Race, n (%) White 174 (87.9) 180 (90.9) Black 17 (8.6) 11 (5.6) Asian 3 (1.5) 5 (2.5) Ethnicity not Hispanic or Latino, n (%) 155 (78.3) 169 (85.4) Mean body weight, kg (SD)* 100.6 (20.8) 98.9 (19.9) Mean BMI, kg/m2 (SD) 35.9 (6.5) 35.3 (5.8) Mean waist circumference, cm (SD) 114.8 (13.7) 114.2 (13.2) Mean HbA1c, % (SD) 7.9 (1.1) 8 (1.0) Mean HbA1c, mmol/mol (SD) 63.0 (11.5) 63.6 (11.3) Mean FPG, mmol/L (SD) 7.8 (2.2) 8.1 (2.5) Mean FPG, mg/dL (SD) 141 (40) 146 (46) Mean diabetes duration, years (SD) 11.4 (6.8) 12.8 (6.9) Mean heart rate, bpm (SD)† 74.0 (10.0) 75.0 (11.0) Mean SBP, mmHg (SD) 129.0 (14.0) 132.0 (16.0) Mean DBP, mmHg (SD) 78.0 (9.0) 78.0 (9.0) Mean total cholesterol, mmol/L (SD) 4.5 (1.0) 4.4 (0.9) Mean total cholesterol, mg/dL (SD) 172 (39) 171 (36) Mean LDL cholesterol, mmol/L (SD) 2.4 (0.9) 2.4 (0.8) Mean LDL cholesterol, mg/dL (SD) 94 (33) 94 (29) Mean HDL cholesterol, mmol/L (SD) 1.2 (0.3) 1.2 (0.3) Mean HDL cholesterol, mg/dL (SD) 45 (12) 45 (11) Mean VLDL cholesterol, mmol/L (SD) 0.9 (0.4) 0.8 (0.4) Mean VLDL cholesterol, mg/dL (SD) 33 (16) 32 (15) Mean triglycerides, mmol/L (SD) 2.0 (1.2) 1.9 (1.0) Mean triglycerides, mg/dL (SD) 174 (105) 168 (89) Mean free fatty acids, mmol/L (SD) 0.6 (0.2) 0.6 (0.3) Mean free fatty acids, mg/dL (SD) 15.9 (6.9) 15.5 (7.3) Antidiabetic medications at screening, n (%) Biguanides 175 (88.4) 176 (88.9) SUs 68 (34.3) 71 (35.9) SGLT2i 44 (22.2) 44 (22.2) Thiazolidinediones 4 (2.0) 6 (3.0) Combination BG-lowering drugs (oral) 4 (2.0) 3 (1.5) α-Glucosidase inhibitors 2 (1.0) 0 (0.0) Other BG-lowering drugs, excluding insulins 1 (0.5) 5 (2.5) Insulins/analogs (injection), n (%) Long-acting 180 (90.9) 184 (92.9) Intermediate-acting 18 (9.1) 14 (7.1) - Table 2
Change in primary and secondary end points from baseline to week 56: treatment policy estimand
Liraglutide 3.0 mg (n = 198) Placebo (n = 198) ETD/OR* (95% CI) P value Primary end points Change in body weight from baseline, % −5.8 −1.5 −4.3 (−5.5; −3.2) <0.0001 Proportion of individuals achieving ≥5% weight loss,* % 51.8 24.0 3.4 (2.2; 5.3) <0.0001 Secondary confirmatory end points Proportion of individuals achieving >10% weight loss,* % 22.8 6.6 4.2 (2.2; 8.2) <0.0001 Change in waist circumference from baseline, cm −5.3 −2.6 −2.7 (−3.9; −1.5) <0.0001 Change in HbA1c from baseline, % −1.1 −0.6 −0.5 (−0.8; −0.3) <0.0001 Change in HbA1c from baseline, mmol/mol −11.9 −6.0 −5.8 (−8.3; −3.4) <0.0001 Change in FPG from baseline, mmol/L −1.0 −0.6 −0.4 (−0.9; 0.1) 0.1502 Change in FPG from baseline, mg/dL −18.4 −11.5 −6.9 ( −16.4; 2.5) 0.1502 Change in SF-36 physical functioning score from baseline 2.7 2.3 0.4 (−1.0; 1.8) 0.5716 Change in IWQOL-Lite for CT physical function domain score from baseline 8.2 5.7 2.5 (−1.5; 6.4) 0.2218 Secondary supportive end points Change in total daily insulin dose from baseline, units 2.8 17.8 −15.0 (−22.0; −8.0) <0.0001 Change in mean daytime glucose value from baseline, mmol/L −2.2 −1.5 −0.7 (−1.1; −0.2) 0.0032 Change in mean daytime glucose value from baseline, mg/dL −39.6 −27.3 −12.4 (−20.6; −4.1) 0.0032 Individuals achieving ≥5% weight loss and HbA1c <7% at week 56* 39.0 13.9 3.9 (2.4; 6.5) <0.0001 Individuals achieving ≥5% weight loss, HbA1c <7%, and no documented symptomatic hypoglycemia at week 56* 17.8 6.2 3.3 (1.66; 6.48) 0.0006 Change in systolic blood pressure from baseline, mmHg −5.6 −1.6 −4.0 (−6.4; −1.5) 0.0014 Change in diastolic blood pressure from baseline, mmHg −2.3 −0.9 −1.4 (−3.0; 0.2) 0.0905 Total cholesterol† 0.97 1.01 0.97 (0.94; 1.00) 0.0463 LDL cholesterol† 0.97 1.01 0.96 (0.91; 1.01) 0.1027 HDL cholesterol† 1.04 1.02 1.02 (0.99; 1.04) 0.2778 VLDL cholesterol† 0.89 0.94 0.94 (0.88; 1.01) 0.0830 Triglycerides† 0.88 0.94 0.94 (0.87; 1.01) 0.0715 Free fatty acids† 0.79 0.84 0.95 (0.85; 1.07) 0.3936 - Table 3
Safety data (on-drug)
Liraglutide 3.0 mg Placebo n (%) E R n (%) E R Number of individuals 195 — — 197 — — Total AEs 180 (92.3) 1,139 578.3 175 (88.8) 1,053 531.2 Serious AEs 16 (8.2) 23 11.7 19 (9.6) 25 12.6 Fatal AEs 0 (0.0) 0 0.0 0 (0.0) 0 0.0 Events leading to treatment discontinuation 15 (7.7) 17 8.6 6 (3.0) 6 3.0 GI AEs 121 (62.1) 408 207.1 92 (46.7) 202 101.9 Nausea 58 (29.7) 105 53.3 23 (11.7) 27 13.6 Constipation 28 (14.4) 36 18.3 17 (8.6) 21 10.6 Diarrhea 45 (23.1) 77 39.1 30 (15.2) 54 27.2 Vomiting 32 (16.4) 53 26.9 12 (6.1) 13 6.6 Abdominal discomfort 11 (5.6) 17 8.6 8 (4.1) 11 5.5 Hypoglycemic episodes 140 (71.8) 1,462 742.3 140 (71.1) 1,859 937.9 ADA classified Severe 3 (1.5) 3 1.5 2 (1.0) 2 1.0 Asymptomatic 116 (59.5) 742 376.7 116 (58.9) 988 498.4 Documented symptomatic 92 (47.2) 662 336.1 102 (51.8) 816 411.7 Pseudohypoglycemia 17 (8.7) 42 21.3 14 (7.1) 31 15.6 Probable symptomatic 8 (4.1) 10 5.1 18 (9.1) 22 11.1 Unclassifiable 2 (1.0) 3 1.5 0 (0.0) 0 0 Safety analysis set. Hypoglycemic episodes were classified using ADA criteria and recorded in individual diaries. Data are from individuals on-drug.
E, number of events; GI, gastrointestinal; n, number of individuals experiencing at least one event; %, percentage of individuals experiencing at least one event; R, event rate per 100 patient-years of exposure.
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