Introduction
Materials and methods
Trial design and study population
Categorical cut-off points for meeting the criteria for metabolic syndrome
Outcomes
Statistical analysis
Results
Patient disposition and characteristics at baseline
Metabolic Syndrome Risk Factors | Tirzepatide 5 mg | Tirzepatide 10 mg | Tirzepatide 15 mg | Comparator | ||||
---|---|---|---|---|---|---|---|---|
Baseline | Primary Endpoint | Baseline | Primary Endpoint | Baseline | Primary Endpoint | Baseline | Primary Endpoint | |
SURPASS-1 monotherapy, N | 105 | 103 | 93 | 95 | ||||
≥ 3 Risk Factors | 77 (73.3) | 58 (55.2) | 69 (67.0) | 49 (47.6) | 70 (75.3) | 36 (38.7) | 73 (76.8) | 68 (71.6) |
WC > 102 cm (M), > 89 cm (F) | 76 (72.4) | 63 (60.0) | 67 (65.0) | 47 (45.6) | 61 (65.6) | 46 (49.5) | 64 (67.4) | 61 (64.2) |
FSG ≥ 100 mg/dL or HbA1c ≥ 5.7% | 105 (100.0) | 83 (79.0) | 103 (100.0) | 84 (81.6) | 93 (100.0) | 60 (64.5) | 95 (100.0) | 94 (98.9) |
SBP > 130 mmHg or DBP > 85 mmHg | 50 (47.6) | 40 (38.1) | 45 (43.7) | 29 (28.2) | 44 (47.3) | 26 (28.0) | 41 (43.2) | 41 (43.2) |
Triglycerides > 150 mg/dL | 52 (49.5) | 37 (35.2) | 52 (50.5) | 31 (30.1) | 45 (48.4) | 23 (24.7) | 53 (55.8) | 48 (50.5) |
HDL < 40 mg/dL (M), < 50 mg/dL (F) | 62 (59.0) | 53 (50.5) | 51 (49.5) | 50 (48.5) | 55 (59.1) | 47 (50.5) | 55 (57.9) | 56 (58.9) |
SURPASS-2 add-on to MET vs SEMA 1 mg, N | 415 | 387 | 389 | 414 | ||||
≥ 3 Risk Factors | 341 (82.2) | 227 (54.7) | 336 (86.8) | 199 (51.4) | 328 (84.3) | 161 (41.4) | 344 (83.1) | 266 (64.3) |
WC > 102 cm (M), > 89 cm (F) | 345 (83.1) | 272 (65.5) | 326 (84.2) | 244 (63.0) | 326 (83.8) | 234 (60.2) | 349 (84.3) | 278 (67.1) |
FSG ≥ 100 mg/dL or HbA1c ≥ 5.7% | 415 (100.0) | 345 (83.1) | 387 (100.0) | 263 (68.0) | 389 (100.0) | 235 (60.4) | 414 (100.0) | 358 (86.5) |
SBP > 130 mmHg or DBP > 85 mmHg | 230 (55.4) | 165 (39.8) | 244 (63.0) | 148 (38.2) | 206 (53.0) | 139 (35.7) | 234 (56.5) | 187 (45.2) |
Triglycerides > 150 mg/dL | 227 (54.7) | 159 (38.3) | 211 (54.5) | 132 (34.1) | 209 (53.7) | 120 (30.8) | 225 (54.3) | 193 (46.6) |
HDL < 40 mg/dL (M), < 50 mg/dL (F) | 230 (55.4) | 183 (44.1) | 216 (55.8) | 170 (43.9) | 229 (58.9) | 176 (45.2) | 239 (57.7) | 201 (48.6) |
SURPASS-3 add-on to MET ± SGLT2i vs iDeg, N | 308 | 291 | 292 | 313 | ||||
≥ 3 Risk Factors | 245 (79.5) | 184 (59.7) | 249 (85.6) | 139 (47.8) | 249 (85.3) | 145 (49.7) | 242 (77.3) | 248 (79.2) |
WC > 102 cm (M), > 89 cm (F) | 255 (82.8) | 212 (68.8) | 248 (85.2) | 170 (58.4) | 252 (86.3) | 173 (59.2) | 253 (80.8) | 263 (84.0) |
FSG ≥ 100 mg/dL or HbA1c ≥ 5.7% | 308 (100.0) | 269 (87.3) | 291 (100.0) | 220 (75.6) | 292 (100.0) | 211 (72.3) | 313 (100.0) | 297 (94.9) |
SBP > 130 mmHg or DBP > 85 mmHg | 185 (60.1) | 131 (42.5) | 173 (59.5) | 109 (37.5) | 180 (61.6) | 112 (38.4) | 201 (64.2) | 192 (61.3) |
Triglycerides > 150 mg/dL | 166 (53.9) | 120 (39.0) | 155 (53.3) | 91 (31.3) | 163 (55.8) | 101 (34.6) | 155 (49.5) | 129 (41.2) |
HDL < 40 mg/dL (M), < 50 mg/dL (F) | 153 (49.7) | 135 (43.8) | 171 (58.8) | 118 (40.5) | 163 (55.8) | 125 (42.8) | 154 (49.2) | 150 (47.9) |
SURPASS-4 ± MET ± SGLT2i ± SU vs iGlar, N | 273 | 276 | 274 | 870 | ||||
≥ 3 Risk Factors | 227 (83.2) | 159 (58.2) | 242 (87.7) | 163 (59.1) | 237 (86.5) | 141 (51.5) | 727 (83.6) | 717 (82.4) |
WC > 102 cm (M), > 89 cm (F) | 222 (81.3) | 174 (63.7) | 227 (82.2) | 163 (59.1) | 226 (82.5) | 158 (57.7) | 674 (77.5) | 709 (81.5) |
FSG ≥ 100 mg/dL or HbA1c ≥ 5.7% | 273 (100.0) | 227 (83.2) | 276 (100.0) | 227 (82.2) | 274 (100.0) | 193 (70.4) | 869 (99.9) | 843 (96.9) |
SBP > 130 mmHg or DBP > 85 mmHg | 169 (61.9) | 134 (49.1) | 180 (65.2) | 155 (56.2) | 179 (65.3) | 138 (50.4) | 590 (64.4) | 609 (70.0) |
Triglycerides > 150 mg/dL | 154 (56.4) | 112 (41.0) | 146 (52.9) | 92 (33.3) | 151 (55.1) | 92 (33.6) | 451 (51.8) | 416 (47.8) |
HDL < 40 mg/dL (M), < 50 mg/dL (F) | 156 (57.1) | 130 (47.6) | 182 (65.9) | 130 (47.1) | 168 (61.3) | 124 (45.3) | 509 (58.5) | 466 (53.6) |
SURPASS-5 add-on to insulin glargine ± MET vs PBO, N | 105 | 105 | 98 | 113 | ||||
≥ 3 Risk Factors | 84 (80.0) | 67 (63.8) | 83 (79.0) | 55 (52.4) | 76 (77.6) | 37 (37.8) | 90 (79.6) | 90 (79.6) |
WC > 102 cm (M), > 89 cm (F) | 92 (87.6) | 79 (75.2) | 87 (82.9) | 76 (72.4) | 81 (82.7) | 69 (70.4) | 90 (79.6) | 92 (81.4) |
FSG ≥ 100 mg/dL or HbA1c ≥ 5.7% | 105 (100.0) | 84 (80.0) | 105 (100.0) | 68 (64.8) | 98 (100.0) | 54 (55.1) | 113 (100.0) | 110 (97.3) |
SBP > 130 mmHg or DBP > 85 mmHg | 73 (69.5) | 59 (56.2) | 78 (74.3) | 55 (52.4) | 69 (70.4) | 31 (31.6) | 84 (74.3) | 80 (70.8) |
Triglycerides > 150 mg/dL | 48 (45.7) | 33 (31.4) | 52 (49.5) | 31 (29.5) | 37 (37.8) | 17 (17.3) | 48 (42.5) | 44 (38.9) |
HDL < 40 mg/dL (M), < 50 mg/dL (F) | 53 (50.5) | 47 (44.8) | 45 (42.9) | 39 (37.1) | 43 (43.9) | 40 (40.8) | 46 (40.7) | 46 (40.7) |
Effect of tirzepatide use on the prevalence of metabolic syndrome in the SURPASS clinical trial program
Effect of tirzepatide use on individual components of metabolic syndrome
Association of tirzepatide use on the prevalence of patients meeting the criteria for metabolic syndrome by weight loss category, SGLT2i or sulfonylurea use, or gender
Metabolic syndrome risk factors | Weight Loss < 5% | Weight Loss > 5% to ≤ 10% | Weight Loss > 10% to ≤ 15% | Weight Loss > 15% to ≤ 20% | Weight Loss > 20% | |||||
---|---|---|---|---|---|---|---|---|---|---|
Baseline | Primary Endpoint | Baseline | Primary Endpoint | Baseline | Primary Endpoint | Baseline | Primary Endpoint | Baseline | Primary Endpoint | |
SURPASS-1 monotherapy, N | 85 | 100 | 57 | 34 | 25 | |||||
≥ 3 Risk Factors | 56 (65.9) | 50 (58.8) | 74 (74.0) | 57 (57.0) | 41 (71.9) | 19 (33.3) | 25 (73.5) | 12 (35.3) | 20 (80.0) | 5 (20.0) |
WC > 102 cm (M), > 89 cm (F) | 57 (67.1) | 53 (62.4) | 69 (69.0) | 52 (52.0) | 35 (61.4) | 24 (42.1) | 24 (70.6) | 16 (47.1) | 19 (76.0) | 11 (44.0) |
FSG ≥ 100 mg/dL or HbA1c ≥ 5.7% | 85 (100.0) | 73 (85.9) | 100 (100.0) | 86 (86.0) | 57 (100.0) | 38 (66.7) | 34 (100.0) | 20 (58.8) | 25 (100.0) | 10 (40.0) |
SBP > 130 mmHg or DBP > 85 mmHg | 47 (55.3) | 36 (42.4) | 38 (38.0) | 34 (34.0) | 27 (47.4) | 14 (24.6) | 19 (55.9) | 9 (26.5) | 8 (32.0) | 2 (8.0) |
Triglycerides > 150 mg/dL | 38 (44.7) | 28 (32.9) | 55 (55.0) | 41 (41.0) | 30 (52.6) | 15 (26.3) | 14 (41.2) | 5 (14.7) | 12 (48.0) | 2 (8.0) |
HDL < 40 mg/dL (M), < 50 mg/dL (F) | 40 (47.1) | 40 (47.1) | 58 (58.0) | 51 (51.0) | 33 (57.9) | 27 (47.4) | 20 (58.8) | 19 (55.9) | 17 (68.0) | 13 (52.0) |
SURPASS-2 add-on to MET vs SEMA 1 mg, N | 268 | 327 | 269 | 187 | 139 | |||||
≥ 3 Risk Factors | 227 (84.7) | 203 (75.7) | 272 (83.2) | 192 (58.7) | 227 (84.4) | 108 (40.1) | 157 (84.0) | 55 (29.4) | 121 (87.1) | 28 (20.1) |
WC > 102 cm (M), > 89 cm (F) | 222 (82.8) | 208 (77.6) | 268 (82.0) | 224 (68.5) | 224 (83.3) | 162 (60.2) | 158 (84.5) | 96 (51.3) | 124 (89.2) | 59 (42.4) |
FSG ≥ 100 mg/dL or HbA1c ≥ 5.7% | 268 (100.0) | 254 (94.8) | 327 (100.0) | 273 (83.5) | 269 (100.0) | 180 (66.9) | 187 (100.0) | 89 (47.6) | 139 (100.0) | 46 (33.1) |
SBP > 130 mmHg or DBP > 85 mmHg | 160 (59.7) | 145 (54.1) | 191 (58.4) | 139 (42.5) | 149 (55.4) | 85 (31.6) | 100 (53.5) | 50 (26.7) | 79 (56.8) | 32 (23.0) |
Triglycerides > 150 mg/dL | 145 (54.1) | 130 (48.5) | 189 (57.8) | 130 (39.8) | 151 (56.1) | 83 (30.9) | 98 (52.4) | 41 (21.9) | 64 (46.0) | 27 (19.4) |
HDL < 40 mg/dL (M), < 50 mg/dL (F) | 148 (55.2) | 126 (47.0) | 177 (54.1) | 151 (46.2) | 159 (59.1) | 109 (40.5) | 110 (58.8) | 89 (47.6) | 80 (57.6) | 53 (38.1) |
SURPASS-3 add-on to MET ± SGLT2i vs iDeg, N | 210 | 207 | 229 | 128 | 117 | |||||
≥ 3 Risk Factors | 174 (82.9) | 163 (77.6) | 171 (82.6) | 124 (59.9) | 195 (85.2) | 109 (47.6) | 108 (84.4) | 47 (36.7) | 95 (81.2) | 25 (21.4) |
WC > 102 cm (M), > 89 cm (F) | 181 (86.2) | 171 (81.4) | 171 (82.6) | 134 (64.7) | 187 (81.7) | 135 (59.0) | 108 (84.4) | 66 (51.6) | 108 (92.3) | 49 (41.9) |
FSG ≥ 100 mg/dL or HbA1c ≥ 5.7% | 210 (100.0) | 205 (97.6) | 207 (100.0) | 181 (87.4) | 229 (100.0) | 182 (79.5) | 128 (100.0) | 82 (64.1) | 117 (100.0) | 50 (42.7) |
SBP > 130 mmHg or DBP > 85 mmHg | 121 (57.6) | 107 (51.0) | 125 (60.4) | 97 (46.9) | 155 (67.7) | 81 (35.4) | 71 (55.5) | 39 (30.5) | 66 (56.4) | 28 (23.9) |
Triglycerides > 150 mg/dL | 120 (57.1) | 120 (57.1) | 109 (52.7) | 81 (39.1) | 121 (52.8) | 65 (28.4) | 75 (58.6) | 32 (25.0) | 59 (50.4) | 14 (12.0) |
HDL < 40 mg/dL (M), < 50 mg/dL (F) | 106 (50.5) | 103 (49.0) | 117 (56.5) | 90 (43.5) | 121 (52.8) | 90 (39.3) | 79 (61.7) | 56 (43.8) | 64 (54.7) | 39 (33.3) |
SURPASS-4 ± MET ± SGLT2i ± SU vs iGlar, N | 212 | 186 | 218 | 115 | 92 | |||||
≥ 3 Risk Factors | 184 (86.8) | 168 (79.2) | 151 (81.2) | 110 (59.1) | 185 (84.9) | 110 (50.5) | 102 (88.7) | 49 (42.6) | 84 (91.3) | 26 (28.3) |
WC > 102 cm (M), > 89 cm (F) | 177 (83.5) | 170 (80.2) | 142 (76.3) | 107 (57.5) | 175 (80.3) | 117 (53.7) | 95 (82.6) | 64 (55.7) | 86 (93.5) | 37 (40.2) |
FSG ≥ 100 mg/dL or HbA1c ≥ 5.7% | 212 (100.0) | 206 (97.2) | 186 (100.0) | 167 (89.8) | 218 (100.0) | 165 (75.7) | 115 (100.0) | 68 (59.1) | 92 (100.0) | 41 (44.6) |
SBP > 130 mmHg or DBP > 85 mmHg | 141 (66.5) | 130 (61.3) | 113 (60.8) | 84 (45.2 | 149 (68.3) | 110 (50.5) | 73 (63.5) | 67 (58.3) | 52 (56.5) | 36 (39.1) |
Triglycerides > 150 mg/dL | 122 (57.5) | 96 (45.3) | 113 (60.8) | 77 (41.4) | 111 (50.9) | 70 (32.1) | 64 (55.7) | 36 (31.3) | 41 (44.6) | 17 (18.5) |
HDL < 40 mg/dL (M), < 50 mg/dL (F) | 124 (58.5) | 119 (56.1) | 110 (59.1) | 87 (46.8) | 131 (60.1) | 96 (44.0) | 78 (67.8) | 47 (40.9) | 63 (68.5) | 35 (38.0) |
SURPASS-5 add-on to insulin glargine ± MET vs PBO, N | 110 | 79 | 57 | 43 | 19 | |||||
≥ 3 Risk Factors | 83 (75.5) | 78 (70.9) | 65 (82.3) | 44 (55.7) | 47 (82.5) | 22 (38.6) | 31 (72.1) | 10 (23.3) | 17 (89.5) | 5 (26.3) |
WC > 102 cm (M), > 89 cm (F) | 96 (87.3) | 93 (84.5) | 67 (84.8) | 60 (75.9) | 48 (84.2) | 41 (71.9) | 32 (74.4) | 19 (44.2) | 17 (89.5) | 11 (57.9) |
FSG ≥ 100 mg/dL or HbA1c ≥ 5.7% | 110 (100.0) | 98 (89.1) | 79 (100.0) | 56 (70.9) | 57 (100.0) | 35 (61.4) | 43 (100.0) | 15 (34.9) | 19 (100.0) | 2 (10.5) |
SBP > 130 mmHg or DBP > 85 mmHg | 77 (70.0) | 72 (65.5) | 55 (69.6) | 40 (50.6) | 43 (75.4) | 15 (26.3) | 31 (72.1) | 13 (30.2) | 14 (73.7) | 5 (26.3) |
Triglycerides > 150 mg/dL | 44 (40.0) | 34 (30.9) | 40 (50.6) | 24 (30.4) | 24 (42.1) | 13 (22.8) | 17 (39.5) | 6 (14.0) | 12 (63.2) | 4 (21.1) |
HDL < 40 mg/dL (M), < 50 mg/dL (F) | 49 (44.5) | 48 (43.6) | 43 (54.4) | 37 (46.8) | 25 (43.9) | 20 (35.1) | 14 (32.6) | 14 (32.6) | 10 (52.6) | 7 (36.8) |
Metabolic Syndrome Risk Factors | Tirzepatide 5 mg | Tirzepatide 10 mg | Tirzepatide 15 mg | Comparator | ||||
---|---|---|---|---|---|---|---|---|
Baseline | Primary Endpoint | Baseline | Primary Endpoint | Baseline | Primary Endpoint | Baseline | Primary Endpoint | |
SURPASS-4 ± MET ± SGLT2i ± SU vs iGlar, N, yes | 156 | 157 | 155 | 466 | ||||
≥ 3 Risk Factors | 128 (82.1) | 91 (58.3) | 141 (89.8) | 96 (61.1) | 140 (90.3) | 84 (54.2) | 396 (85.0) | 392 (84.1) |
WC > 102 cm (M), > 89 cm (F) | 124 (79.5) | 100 (64.1) | 129 (82.2) | 96 (61.1) | 128 (82.6) | 91 (58.7) | 359 (77.0) | 385 (82.6) |
FSG ≥ 100 mg/dL or HbA1c ≥ 5.7% | 156 (100.0) | 129 (82.7) | 157 (100.0) | 133 (84.7) | 155 (100.0) | 119 (76.8) | 466 (100.0) | 460 (98.7) |
SBP > 130 mmHg or DBP > 85 mmHg | 96 (61.5) | 76 (48.7) | 107 (68.2) | 85 (54.1) | 107 (69.0) | 81 (52.3) | 296 (63.5) | 333 (71.5) |
Triglycerides > 150 mg/dL | 93 (59.6) | 68 (43.6) | 82 (52.2) | 54 (34.4) | 95 (61.3) | 51 (32.9) | 248 (53.2) | 230 (49.4) |
HDL < 40 mg/dL (M), < 50 mg/dL (F) | 92 (59.0) | 77 (49.4) | 102 (65.0) | 77 (49.0) | 94 (60.6) | 70 (45.2) | 279 (59.9) | 261 (56.0) |
SURPASS-4 ± MET ± SGLT2i ± SU vs iGlar, N, no | 117 | 119 | 119 | 404 | ||||
≥ 3 Risk Factors | 99 (84.6) | 68 (58.1) | 101 (84.9) | 67 (56.3) | 97 (81.5) | 57 (47.9) | 331 (81.9) | 325 (80.4) |
WC > 102 cm (M), > 89 cm (F) | 98 (83.8) | 74 (63.2) | 98 (82.4) | 67 (56.3) | 98 (82.4) | 67 (56.3) | 315 (78.0) | 324 (80.2) |
FSG ≥ 100 mg/dL or HbA1c ≥ 5.7% | 117 (100.0) | 98 (83.8) | 119 (100.0) | 94 (79.0) | 119 (100.0) | 74 (62.2) | 403 (99.8) | 383 (94.8) |
SBP > 130 mmHg or DBP > 85 mmHg | 73 (62.4) | 58 (49.6) | 73 (61.3) | 70 (58.8) | 72 (60.5) | 57 (47.9) | 264 (65.3) | 276 (68.3) |
Triglycerides > 150 mg/dL | 61 (52.1) | 44 (37.6) | 64 (53.8) | 38 (31.9) | 56 (47.1) | 41 (34.5) | 203 (50.2) | 186 (46.0) |
HDL < 40 mg/dL (M), < 50 mg/dL (F) | 64 (54.7) | 53 (45.3) | 80 (67.2) | 53 (44.5) | 74 (62.2) | 54 (45.4) | 230 (56.9) | 205 (50.7) |