Table 1.
Efficacy of Semaglutide Across the Phase 3 Clinical Trials.
| Study | Patient Population | Duration (weeks) | Treatment | Mean Baseline HbA1c and Body Weight | Change in Mean HbA1c (%) From Baseline to End of Treatment | Change in Mean Body Weight (kg) From Baseline to End of Treatment |
|---|---|---|---|---|---|---|
| SUSTAIN 1,8 NCT02054897 | Age ⩾18 yo, T2DM, treated with diet and exercise alone for ⩾30 days before screening, HbA1c = 7.0% to 10.0% | 30 | • 0.5 mg SC semaglutide QW • 1.0 mg SC semaglutide QW • Volume-matched SC placebo QW |
• 8.05% • 91.93 kg |
• 0.5 mg semaglutide: −1.45 • ETD versus placebo (95% CI = −1.43 [−1.71 to −1.15], P < .0001) • 1.0 mg semaglutide: −1.55 • ETD versus placebo (95% CI = −1.53 [−1.81 to −1.25], P < .001) |
• 0.5 mg semaglutide: −3.73 • ETD versus placebo (95% CI = −2.75 −3.92 to −1.58], P < .0001) • 1.0 mg semaglutide: −4.53 • ETD versus placebo (95% CI = −3.56 [−4.74 to −2.38], P < .0001) |
| SUSTAIN 2,9 NCT01930188 | Age ⩾18 yo (or ⩾20 yo in Japan), T2DM, HbA1c = 7.0% to 10.5% for 90 days before screening, treatment with metformin (⩾1500 mg), pioglitazone (⩾30 mg), rosiglitazone (⩾4 mg), or combo of metformin + pioglitazone, or metformin + rosiglitazone | 56 | • 0.5 mg SC semaglutide QW + oral placebo QD • 1.0 mg SC semaglutide QW + oral placebo QD • 100 mg sitagliptin QD + SC volume-matched (0.5 mg and 1.0 mg) placebo QW |
• 8.1% • 89.5 kg |
• 0.5 mg semaglutide: −1.3 • ETD versus sitagliptin (95% CI = −0.77 [−0.92 to −0.62], P < .0001) • 1.0 mg semaglutide: −1.6 • ETD versus sitagliptin (95% CI = −1.06 [−1.21 to −0.91), P < .0001) • 100 mg sitagliptin: −0.5 |
• 0.5 mg semaglutide: −4.3 • ETD versus sitagliptin (95% CI = −2.35 [−3.06 to −1.63], P < .0001) • 1.0 mg semaglutide: −6.1 • ETD versus sitagliptin (95% CI = −4.20 [−4.91 to −3.49), P < .0001) • 100 mg sitagliptin: −1.9 |
| SUSTAIN 3,10 NCT01885208 | Age ⩾18 yo, insulin-naïve T2DM, HbA1c = 7.0% to 10.5%, treatment with 1 or 2 oral PTD (metformin ⩾1500 mg or max tolerated dose, and/or TZD, and/or SFU [at least ½ of max dose allowed]) for ⩾90 days before screening | 56 | • 1.0 mg SC semaglutide QW • 2.0 mg exenatide ER QW |
• 8.3% • 95.8 kg |
• 1.0 mg semaglutide: −1.5 • 2.0 mg exenatide ER: −0.9 • ETD (95% CI = −0.62 [−0.80 to −0.44], P < .0001) |
• 1.0 mg semaglutide: −5.6 • 2.0 mg exenatide ER: −1.9 • ETD (95% CI = −3.78 [−4.58 to −2.98], P < .0001) |
| SUSTAIN 4,11 NCT02128932 | Age ⩾18 yo, T2DM, HbA1c = 7.0% to 10.0%, treatment with metformin alone or in combo with SFU for ⩾90 days before screening | 30 | • 0.5 mg SC semaglutide QW • 1.0 mg SC semaglutide QW • Insulin glargine U100 once daily initiated at 10 units and titrated to target FPG of 72 to 99 mg/dL |
• 8.17% • 93.45 kg |
• 0.5 mg semaglutide: −1.21 • ETD versus insulin glargine (95% CI = −0.38 [−0.52 to −0.24], P < .0001) • 1.0 mg semaglutide: −1.64 • ETD versus insulin glargine (95% CI = −0.81 [−0.96 to −0.67], P < .0001) • Insulin glargine: −0.83 |
• 0.5 mg semaglutide: −3.47 • ETD versus insulin glargine (95% CI = −4.62 [−5.27 to −3.96], P < .0001) • 1.0 mg semaglutide: −5.17 • ETD versus insulin glargine (95% CI = −6.33 [−6.99 to −5.67], P < .0001) • Insulin glargine: 1.15 |
| SUSTAIN 5,12 NCT02305381 | Age ⩾18 yo, T2DM, HbA1c = 7.0% to 10.0%, treatment with basal insulin alone or in combo with metformin | 30 | • 0.5 mg SC semaglutide QW • 1.0 mg SC semaglutide QW • SC volume-matched (0.5 mg and 1.0 mg) placebo QW |
• 8.4% • 91.7 kg |
• 0.5 mg semaglutide: −1.4 • ETD versus placebo (95% CI = −1.35 [−1.61 to −1.10], P < .0001) • 1.0 mg semaglutide: −1.8 • ETD versus placebo (95% CI = −1.75 [−2.01 to −1.50], P < .0001) • Placebo: −0.1 |
• 0.5 mg semaglutide: −3.7 • ETD versus placebo (95% CI = −2.31 [−3.33 to −1.29], P < .0001) • 1.0 mg semaglutide: −6.4 • ETD versus placebo (95% CI = −5.06 [−6.08 to −4.04], P < .0001) • Placebo: −1.4 |
| SUSTAIN 6,13 NCT01720446 | Age ⩾50 yo, T2DM, HbA1c ⩾7%, established CV disease (previous CVD, CeVD, or PVD), chronic HF (NYHA class II or III), or CKD ⩾stage 3 or age⩾60 yo with ⩾1 CV risk factor, had not been treated with an antihyperglycemic drug or had been treated with ⩽2 oral PTD, with or without basal or premixed insulin Primary endpoint was composite of first occurrence of CV death, nonfatal MI, or nonfatal CVA |
104 | • 0.5 mg SC semaglutide QW • 1.0 mg SC semaglutide QW • Volume-matched SC placebo QW |
• 8.7% • 92.1 kg |
• 0.5 mg semaglutide: −1.1 • 0.5 mg placebo: −0.4 • ETD versus placebo (95% CI = −0.66 [−0.80 to −0.52], P < .001) • 1.0 mg semaglutide: −1.4 • 1.0 mg placebo: −0.4 • ETD versus placebo (95% CI = −1.05 [−1.19 to −0.91], P < .001) |
• 0.5 mg semaglutide: −3.6 • 0.5 mg placebo: −0.7 • ETD versus placebo (95% CI = −2.87 [−3.47 to −2.28], P < .001) • 1.0 mg semaglutide: −4.9 • 1.0 mg placebo: −0.5 • ETD versus placebo (95% CI = −4.35 [−4.94 to −3.75], P < .001) |
| SUSTAIN 7,14 NCT02648204 | Age ⩾18 yo, T2DM, HbA1c = 7.0% to 10.5%, treatment with metformin (minimum of 1500 mg/day or max tolerated dose) for 90 days prior to screening | 40 | • 0.5 mg SC semaglutide QW • 1.0 mg SC semaglutide QW • 0.75 mg dulaglutide QW • 1.5 mg dulaglutide QW |
• 8.2% • 95.2 kg |
• 0.5 mg semaglutide: −1.5 • 0.75 mg dulaglutide: −1.1 • ETD (95% CI = −0.40 [−0.55 to −0.25], P < .0001) • 1.0 mg semaglutide: −1.8 • 1.5 mg dulaglutide: −1.4 • ETD (95% CI = −0.41 [−0.57 to −0.25], P < .001) |
• 0.5 mg semaglutide: −4.6 • 0.75 mg dulaglutide: −2.3 • ETD (95% CI = −2.26 [−3.02 to −1.51], P < .0001) • 1.0 mg semaglutide: −6.5 • 1.5 mg dulaglutide: −3.0 • ETD (95% CI = −3.55 [−4.32 to −2.78], P < .0001) |
| SUSTAIN JP PTD,19 NCT02207374 | Age ⩾20 yo, Japanese, T2DM, HbA1c = 7.0% to 10.5%, treatment with either diet and exercise for at least 30 days before visit 1 (week 2) or on oral PTD monotherapy (either of SFU, glinide, α-GI, or TZD) in addition to diet and exercise for at least 60 days before visit 1 (week 2) Primary outcome was number of AE |
56 | • 0.5 mg SC semaglutide QW • 1.0 mg SC semaglutide QW • 1 additional oral PTD (DPP-4 inhibitor, SFU, glinide, biguanide, α-GI, or TZD) + pretrial oral PTD monotherapy, if any |
• 8.1% • 71.5 kg |
• 0.5 mg semaglutide: −1.7 • ETD versus additional oral PTD (95% CI = −1.08 [−1.24 to −0.91], P < .0001) • 1.0 mg semaglutide: −2.0 • ETD versus additional oral PTD (95% CI = −1.37 [−1.53 to −1.20], P< .0001) • Additional oral PTD: −0.7 |
• 0.5 mg semaglutide: −1.4 • ETD versus additional oral PTD (95% CI = −1.84 [−2.67 to −1.01], P < .001) • 1.0 mg semaglutide: −3.2 • ETD versus additional oral PTD (95% CI = −3.59 [−4.43 to −2.75], P < .001) • Additional oral PTD: 0.4 |
| SUSTAIN JP Mono,20 NCT02254291 | Age ⩾20 yo, T2DM, Japanese, HbA1c = 6.5% to 9.5% if treated with either diet and exercise therapy + oral PTD monotherapy or HbA1c = 7.0% to 10.5% if treated with diet and exercise therapy only for ⩾30 days before screening Primary outcome was number of AE |
30 | • 0.5 mg SC semaglutide QW • 1.0 mg SC semaglutide QW • 100 mg sitagliptin QD |
• 8.1% • 69.3 kg |
• 0.5 mg semaglutide: −1.9 • ETD versus sitagliptin (95% CI = −1.13 [−1.32 to −0.94], P < .0001) • 1.0 mg semaglutide: −2.2 • ETD versus sitagliptin (95% CI = −1.44 [−1.63 to −1.24], P < .0001) • 100 mg sitagliptin: −0.7 |
• 0.5 mg semaglutide: −2.2 • ETD versus sitagliptin (95% CI = −2.22 [−3.02 to −1.42], P < .0001) • 1.0 mg semaglutide: −3.9 • ETD versus sitagliptin (95% CI = −3.88 [−4.70 to −3.07], P < .0001) • 100 mg sitagliptin: 0.0 |
| PIONEER 1,25,26 NCT02906930 | Age ⩾18 yo (or ⩾20 yo for Japan or ⩾19 yo for Algeria), T2DM, HbA1c = 7.0% to 9.5%, treatment with diet and exercise for ⩾30 days before screening | 26 | • 3 mg oral semaglutide QD • 7 mg oral semaglutide QD • 14 mg oral semaglutide QD • Oral placebo QD |
• 8.0% • 88 kg |
• 3 mg semaglutide: −0.8 • 7 mg semaglutide: −1.3 • 14 mg semaglutide: −1.5 • Placebo: −0.1 |
• 3 mg semaglutide: −1.7 • 7 mg semaglutide: −2.5 • 14 mg semaglutide: −4.1 • Placebo: −1.5 |
| PIONEER 2,27,28 NCT02863328 | Age ⩾18 yo, T2DM, HbA1c = 7.0% to 10.5%, treatment with metformin (at least 1500 mg or max tolerated dose) ⩾90 days before screening | 52 | • 14 mg oral semaglutide QD • 25 mg empagliflozin QD |
• N/A • N/A |
• 14 mg semaglutide: −1.4*; −1.3 • 25 mg empagliflozin: −0.9*; −0.8 *HbA1c at 26 weeks |
• 14 mg semaglutide: −4.2*; −4.7 • 25 mg empagliflozin: −3.8*; −3.8 *Weight loss at 26 weeks |
Abbreviations: α-GI, alpha-glucosidase inhibitor; AE, adverse events; CeVD, cerebrovascular disease; CI, confidence interval; CKD, chronic kidney disease; CV, cardiovascular; CVA, cerebrovascular attack (stroke); CVD, cardiovascular disease; DPP-4, dipeptidyl peptidase-4; ER, extended release; ETD, estimated treatment difference; FPG, fasting plasma glucose; glinide, meglitinides; HbA1c, hemoglobin A1c; HF, heart failure; MI, myocardial infarction; N/A, not available; NYHA, New York Heart Association; PTD, pharmacologic therapy for diabetes; PVD, peripheral vascular disease; QD, once daily; QW, once weekly; SC, subcutaneous; SFU, sulfonylurea; SGLT-2, sodium-glucose cotransporter-2; TZD, thiazolidinedione; yo, years old.