Table 2.
Safety assessments
| Variable | Week 26 | Week 52 | ||||
|---|---|---|---|---|---|---|
| Dulaglutide | Glargine | Dulaglutide | Glargine | |||
| 1.5 mg | 0.75 mg | 1.5 mg | 0.75 mg | |||
| (n = 203) | (n = 201) | (n = 198) | (n = 203) | (n = 201) | (n = 198) | |
| Death, n (%) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Serious adverse events, n (%) | 8 (3.9) | 6 (3.0) | 4 (2.0) | 17 (8.4) | 13 (6.5) | 8 (4.0) |
| TEAEs (patients with ≥ 1), n (%) | 128 (63.1) | 123 (61.2) | 94 (47.5) | 142 (70.0) | 142 (70.6) | 116 (58.6) |
| TEAEs in at least 5% of patients in any treatment group, n (%) | ||||||
| Gastrointestinal AEs | 64 (31.5) | 51 (25.4) | 15 (7.6) | 65 (32.0) | 54 (26.9) | 16 (8.1) |
| Diarrhea | 31 (15.3) | 19 (9.5) | 6 (3.0) | 32 (15.8) | 23 (11.4) | 7 (3.5) |
| Nausea | 20 (9.9) | 9 (4.5) | 2 (1.0) | 20 (9.9) | 9 (4.5) | 2 (1.0) |
| Abdominal distention | 18 (8.9) | 12 (6.0) | 0 (0.0) | 18 (8.9) | 12 (6.0) | 0 (0.0) |
| Vomiting | NA | NA | NA | 11 (5.4) | 3 (1.5) | 1 (0.5) |
| Infections and infestations | 25 (12.3) | 20 (10.0) | 22 (11.1) | 37 (18.2) | 32 (15.9) | 34 (17.2) |
| Nasopharyngitis | NA | NA | NA | 13 (6.4) | 10 (5.0) | 11 (5.6) |
| Upper respiratory tract infection | NA | NA | NA | 7 (3.4) | 9 (4.5) | 13 (6.6) |
| Investigations | 30 (14.8) | 26 (12.9) | 16 (8.1) | 47 (23.2) | 37 (18.4) | 22 (11.1) |
| Lipase increased | 19 (9.4) | 16 (8.0) | 2 (1.0) | 25 (12.3) | 18 (9.0) | 2 (1.0) |
| Metabolism and nutrition disorders | 56 (27.6) | 56 (27.9) | 39 (19.7) | 59 (29.1) | 66 (32.8) | 49 (24.7) |
| Hyperlipidemia | 38 (18.7) | 38 (18.9) | 31 (15.7) | 40 (19.7) | 43 (21.4) | 39 (19.7) |
| Decreased appetite | 18 (8.9) | 11 (5.5) | 0 (0.0) | 18 (8.9) | 11 (5.5) | 0 (0.0) |
| Discontinuation due to AE, n (%) | 6 (3.0) | 6 (3.0) | 1 (0.5) | 7 (3.4) | 10 (5.0) | 2 (1.0) |
| Total hypoglycemic incidence, n (%)† | 34 (16.7)* | 32 (15.9)* | 55 (27.8) | 41 (20.2)* | 38 (18.9)* | 64 (32.3) |
| Total hypoglycemia rate, events/patient/year (SD)‡ | 0.90 (3.864) | 0.75 (2.379) | 1.41 (3.882) | 0.64 (3.503) | 0.54 (1.709)* | 1.11 (3.443) |
| Severe hypoglycemia, n (%) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Nocturnal hypoglycemia incidence, n (%)† | 14 (6.9) | 8 (4.0)* | 21 (10.6) | 15 (7.4)* | 8 (4.0)* | 28 (14.1) |
| Nocturnal hypoglycemia rate, events/patient/year (SD)‡ | 0.22 (0.969) | 0.14 (0.811)* | 0.38 (1.527) | 0.11 (0.486) | 0.09 (0.523)* | 0.29 (1.270) |
| Documented symptomatic hypoglycemic incidence, n (%)† | 18 (8.9) | 15 (7.5)* | 29 (14.6) | 20 (9.9)* | 19 (9.5)* | 36 (18.2) |
| Asymptomatic hypoglycemic incidence, n (%)† | 17 (8.4) | 13 (6.5) | 23 (11.6) | 21 (10.3) | 16 (8.0)* | 30 (15.2) |
| Probable hypoglycemic incidence, n (%) | 8 (3.9) | 12 (6.0) | 16 (8.1) | 9 (4.4) | 13 (6.5) | 18 (9.1) |
| Pancreatic enzymes | ||||||
| Pancreatic enzymes, mean (SD), units/L | ||||||
| Lipase (baseline) | 39.88 (21.068) | 40.63 (23.891) | 40.59 (22.874) | 39.88 (21.068) | 40.63 (23.891) | 40.59 (22.874) |
| Lipase Δ | 11.01 (36.878) | 10.48 (28.834) | − 3.49 (21.563) | 10.54 (28.156) | 11.46 (32.976) | − 4.50 (19.330) |
| Total amylase (baseline) | 56.97 (18.894) | 58.23 (20.505) | 59.05 (24.184) | 56.97 (18.894) | 58.23 (20.505) | 59.05 (24.184) |
| Total amylase Δ | 7.48 (18.566) | 7.86 (16.025) | 0.03 (17.258) | 7.96 (16.282) | 8.40 (19.051) | − 0.37 (15.707) |
| Pancreatic amylase (baseline) | 25.30 (10.751) | 25.51 (10.843) | 25.44 (11.164) | 25.30 (10.751) | 25.51 (10.843) | 25.44 (11.164) |
| Pancreatic amylase Δ | 5.84 (14.611) | 5.18 (11.056) | − 0.09 (7.721) | 5.23 (12.893) | 5.45 (13.971) | − 0.76 (8.063) |
| Pancreatic enzymes, n (%) patients with ≥ 3 × ULN§ | ||||||
| Lipase (baseline) | 1 (0.5) | 2 (1.0) | 0 (0.0) | 1 (0.5) | 2 (1.0) | 0 (0.0) |
| Lipase | 3 (1.5) | 2 (1.0) | 1 (0.5) | 4 (2.0) | 4 (2.0) | 0 (0.0) |
| Total amylase (baseline) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Total amylase | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Pancreatic amylase (baseline) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Pancreatic amylase | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
| Serum calcitonin, mean (SD), pmol/L | 0.57 (0.512) | 0.63 (0.632) | 0.60 (0.565) | 0.57 (0.512) | 0.63 (0.632) | 0.60 (0.565) |
| Serum calcitonin, median, pmol/L | 0.29 | 0.29 | 0.29 | 0.29 | 0.29 | 0.29 |
| Serum calcitonin Δ, mean (SD) | 0.59 (0.591) | 0.56 (0.530) | 0.60 (0.593) | 0.53 (0.503) | 0.53 (0.559) | 0.53 (0.561) |
| Serum calcitonin Δ, median | 0.29 | 0.29 | 0.29 | 0.29 | 0.29 | 0.29 |
| Vital signs | ||||||
| Sitting blood pressure, mmHg | ||||||
| Systolic (baseline) | 131.89 (13.612) | 129.78 (13.164) | 131.79 (14.954) | 131.89 (13.612) | 129.78 (13.164) | 131.79 (14.954) |
| Systolic Δ | − 6.69 (12.597) | − 3.82 (12.467) | − 2.72 (13.402) | − 2.79 (11.706) | − 1.43 (12.533) | 0.06 (11.975) |
| Diastolic (baseline) | 78.26 (8.949) | 77.94 (9.629) | 79.30 (8.818) | 78.26 (8.949) | 77.94 (9.629) | 79.30 (8.818) |
| Diastolic Δ | − 1.98 (8.117) | − 1.39 (8.089) | − 1.97 (8.800) | − 0.48 (8.057) | 0.02 (7.747) | − 1.30 (8.778) |
| Sitting pulse rate (baseline), bpm | 76.30 (10.537) | 77.54 (9.795) | 77.28 (10.014) | 76.30 (10.537) | 77.54 (9.795) | 77.28 (10.014) |
| Pulse rate Δ | 4.60 (8.769) | 3.01 (8.304) | − 0.49 (9.022) | 3.95 (8.603) | 2.91 (9.034) | − 0.09 (8.142) |
| Treatment-emergent dulaglutide antidrug antibody, n (%) | NA | NA | NA | 6 (3.0) | 10 (5.0) | 1 (0.5) |
| Neutralizing dulaglutide | NA | NA | NA | 2 (1.0) | 4 (2.0) | 0 (0.0) |
| Neutralizing native-sequence GLP-1 | NA | NA | NA | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Hypoglycemic episode is defined as a combination of the following: an episode with blood glucose concentration of ≤ 70 mg/dL (≤ 3.9 mmol/L) with (documented symptomatic) or without symptoms (asymptomatic), an episode during which symptoms are indicative of hypoglycemia but are not accompanied by a blood glucose concentration of ≤ 70 mg/dL (≤ 3.9 mmol/L) (probable symptomatic), or a severe hypoglycemic episode (requiring medical assistance as determined by the investigator) and an episode that occurred between bedtime and waking (nocturnal hypoglycemia)
Δ change from baseline at week 26 or week 52, AE adverse event, GLP-1 glucagon-like peptide-1, OAM oral antihyperglycemic medication, SD standard deviation, TEAE treatment-emergent adverse event, ULN upper limit of normal
†P value is based on Fisher’s exact test, on the incidence rate of patients with analyzed hypoglycemia episodes
‡P value for overall is based on a negative binomial regression model: patient’s hypoglycemia count = OAM strata + treatment + country, with log of (patient’s total number of days of exposure/365.25) as an offset variable
§Patients with at least 1 value ≥ 3 × ULN during the assessed time period
* P value is < 0.05 for dulaglutide vs insulin glargine