27 May 2025 : Database Analysis
Glucagon-Like Peptide-1 Receptor Agonists Lead to Gastrointestinal Benefits in Patients with Type 2 Diabetes: A Real-World Study
Jung-Hui Hsu AEF 1, Hsueh-Fen Bai ADF 2, Mon-Ting Chen CD 3, Yu-Wei Fang AD 3,4,5, Jing-Tong Wang CE 3,4, Chieh-Yu Liu
DF 3, Ming-Hsein Tsai ADEF 3,4,5*
DOI: 10.12659/MSM.946935
Med Sci Monit 2025; 31:e946935
Table 1 Baseline characteristics of study population.
| Parameter | Before matching | After matching | ||||
|---|---|---|---|---|---|---|
| GLP1-RA (n=228,703) | DPP4i (n=202,303) | SMD | GLP1-RA (n=127,216) | DPP4i (n=127,216) | SMD | |
| Age at Index (years), mean±SD | 56.3±12.7 | 62.8±12.6 | 0.520 | 59.8±11.9 | 60.2±12.5 | 0.031 |
| Male, n (%) | 134,108 (58.6) | 80,636 (39.9) | 0.382 | 68,982 (54.2) | 69,954 (55) | 0.015 |
| BMI (Kg/m), mean±SD | 36.1±8.3 | 31.5±7.6 | 0.586 | 34±7.8 | 33.1±7.5 | 0.113 |
| Tobacco use | 10,091 (4.4) | 7,328 (3.6) | 0.040 | 5,817 (4.6) | 5,888 (4.6) | 0.003 |
| Nicotine dependence | 23,876 (10.4) | 17,200 (8.5) | 0.066 | 13,592 (10.7) | 13,826 (10.9) | 0.006 |
| Alcohol-related disorders | 3,827 (1.7) | 3,624 (1.8) | 0.009 | 2,427 (1.9) | 2,530 (2) | 0.006 |
| White | 104,046 (45.5) | 106,353 (52.6) | 0.142 | 62,886 (49.4) | 63,487 (49.9) | 0.009 |
| African American | 45,516 (19.9) | 29,541 (14.6) | 0.141 | 24,282 (19.1) | 24,809 (19.5) | 0.010 |
| Asian | 9,617 (4.2) | 17,662 (8.7) | 0.185 | 7,504 (5.9) | 7,466 (5.9) | 0.001 |
| Dyslipidemia | 162,851 (71.2) | 138,327 (68.4) | 0.062 | 91,220 (71.7) | 91,440 (71.9) | 0.004 |
| Hypertensive diseases | 169,006 (73.9) | 146,947 (72.6) | 0.028 | 96,271 (75.7) | 96,859 (76.1) | 0.011 |
| Ischemic heart diseases | 42,179 (18.4) | 46,337 (22.9) | 0.110 | 27,156 (21.3) | 27,698 (21.8) | 0.010 |
| Hepatic failure | 20,851 (9.1) | 20,958 (10.4) | 0.042 | 13,304 (10.5) | 13,690 (10.8) | 0.010 |
| Cardiomyopathy | 7,587 (3.3) | 6,252 (3.1) | 0.013 | 4,520 (3.6) | 4,692 (3.7) | 0.007 |
| Nonrheumatic mitral valve disorders | 6,694 (2.9) | 7,518 (3.7) | 0.044 | 4,422 (3.5) | 4,583 (3.6) | 0.007 |
| Atrial fibrillation and flutter | 15,246 (6.7) | 17,397 (8.6) | 0.073 | 10,470 (8.2) | 10,920 (8.6) | 0.013 |
| Other cardiac arrhythmias | 13,043 (5.7) | 12,453 (6.2) | 0.019 | 7,978 (6.3) | 8,266 (6.5) | 0.009 |
| Aortic aneurysm and dissection | 1,868 (0.8) | 2,134 (1.1) | 0.025 | 1,291 (1) | 1,335 (1) | 0.003 |
| Peripheral vessel disease | 9,309 (4.1) | 8,691 (4.3) | 0.011 | 5,921 (4.7) | 6,118 (4.8) | 0.007 |
| Chronic kidney disease | 34,835 (15.2) | 38,035 (18.8) | 0.095 | 23,125 (18.2) | 23,445 (18.4) | 0.007 |
| Disorders of calcium | 5,860 (2.6) | 5,023 (2.5) | 0.005 | 3,468 (2.7) | 3,607 (2.8) | 0.007 |
| Disorders of phosphorus | 2,362 (1) | 3,157 (1.6) | 0.047 | 1,739 (1.4) | 1,835 (1.4) | 0.006 |
| Disorders of magnesium | 7,363 (3.2) | 8,148 (4) | 0.043 | 5,085 (4) | 5,299 (4.2) | 0.009 |
| Disorders of iron | 653 (0.3) | 395 (0.2) | 0.018 | 335 (0.3) | 331 (0.3) | 0.001 |
| Lymphatic vessels disease | 16,330 (7.1) | 12,144 (6) | 0.046 | 8,984 (7.1) | 9,214 (7.2) | 0.007 |
| Chronic lower respiratory diseases | 40,565 (17.7) | 30,073 (14.9) | 0.078 | 22,091 (17.4) | 22,010 (17.3) | 0.002 |
| Upper respiratory tract disease | 28,338 (12.4) | 18,182 (9) | 0.110 | 14,205 (11.2) | 14,264 (11.2) | 0.001 |
| Soft-tissue disorders | 62,183 (27.2) | 38,543 (19.1) | 0.194 | 31,372 (24.7) | 31,442 (24.7) | 0.001 |
| Cholelithiasis | 4,367 (1.9) | 4,678 (2.3) | 0.028 | 2,649 (2.1) | 2,760 (2.2) | 0.006 |
| Cholecystitis | 1,047 (0.5) | 1,149 (0.6) | 0.015 | 642 (0.5) | 660 (0.5) | 0.002 |
| Other gallbladder diseases | 1,567 (0.7) | 1,433 (0.7) | 0.003 | 936 (0.7) | 969 (0.8) | 0.003 |
| Other biliary tract diseases | 1,096 (0.5) | 1,559 (0.8) | 0.037 | 792 (0.6) | 778 (0.6) | 0.001 |
| Acute pancreatitis | 1,212 (0.5) | 1,541 (0.8) | 0.029 | 822 (0.6) | 832 (0.7) | 0.001 |
| Other pancreas diseases | 1,727 (0.8) | 2,103 (1) | 0.030 | 1,181 (0.9) | 1,235 (1) | 0.004 |
| Peritonitis | 634 (0.3) | 853 (0.4) | 0.024 | 458 (0.4) | 449 (0.4) | 0.001 |
| Lipid-modifying agents | 151,686 (66.3) | 143,540 (71) | 0.100 | 89,608 (70.4) | 89,734 (70.5) | 0.002 |
| Insulin | 111,495 (48.8) | 81,044 (40.1) | 0.176 | 58,186 (45.7) | 58,327 (45.8) | 0.002 |
| Biguanides | 150,946 (66) | 146,214 (72.3) | 0.136 | 87,033 (68.4) | 86,413 (67.9) | 0.010 |
| Sulfonylureas | 56,390 (24.7) | 66,875 (33.1) | 0.186 | 37,838 (29.7) | 37,828 (29.7) | <0.001 |
| SGLT2i | 55,906 (24.4) | 35,347 (17.5) | 0.172 | 27,873 (21.9) | 26,540 (20.9) | 0.026 |
| Thiazolidinediones | 12,387 (5.4) | 13,774 (6.8) | 0.058 | 7,749 (6.1) | 7,617 (6) | 0.004 |
| Agents on RAS | 133,100 (58.2) | 119,125 (58.9) | 0.014 | 76,751 (60.3) | 77,235 (60.7) | 0.008 |
| Beta-blocker | 78,982 (34.5) | 79,046 (39.1) | 0.094 | 48,697 (38.3) | 49,208 (38.7) | 0.008 |
| Calcium channel blockers | 60,140 (26.3) | 72,442 (35.8) | 0.207 | 38,321 (30.1) | 38,414 (30.2) | 0.002 |
| Diuretics | 86,285 (37.7) | 69,532 (34.4) | 0.070 | 48,490 (38.1) | 48,848 (38.4) | 0.006 |
| Antiarrhythmics | 73,706 (32.2) | 54,538 (27) | 0.116 | 40,567 (31.9) | 41,008 (32.2) | 0.007 |
| Corticosteroids, systemic | 91,070 (39.8) | 68,260 (33.7) | 0.126 | 49,181 (38.7) | 49,202 (38.7) | <0.001 |
| Antacids | 76,562 (33.5) | 79,320 (39.2) | 0.119 | 48,011 (37.7) | 48,927 (38.5) | 0.015 |
| Anti-inflammatory agents | 82,020 (35.9) | 58,884 (29.1) | 0.145 | 42,743 (33.6) | 42,519 (33.4) | 0.004 |
| Laxatives | 65,750 (28.7) | 65,499 (32.4) | 0.079 | 40,767 (32) | 41,433 (32.6) | 0.011 |
| Thyroid therapy | 29,133 (12.7) | 21,147 (10.5) | 0.071 | 15,865 (12.5) | 15,986 (12.6) | 0.003 |
| Anti-gout agents | 10,929 (4.8) | 13,064 (6.5) | 0.073 | 6,986 (5.5) | 6,945 (5.5) | 0.001 |
| Hemoglobin A1c (%) | 8.4±2.1 | 8.1±2 | 0.145 | 8.4±2 | 8.3±2 | 0.044 |
| eGFR (mL/min/1.73 m2) | 83.8±25.8 | 79.8±26.8 | 0.150 | 81±25 | 81.7±26.3 | 0.027 |
| Sodium (mmol/L) | 138.2±3 | 138±3.5 | 0.060 | 138.3±3.1 | 138.1±3.3 | 0.052 |
| Potassium (mmol/L) | 4.3±0.5 | 4.2±0.5 | 0.085 | 4.3±0.5 | 4.2±0.5 | 0.063 |
| Chloride (mmol/L) | 101.7±5.1 | 101.8±4.9 | 0.012 | 101.8±5.1 | 101.7±4.8 | 0.024 |
| Calcium (mg/dL) | 9.4±0.6 | 9.3±0.7 | 0.197 | 9.4±0.6 | 9.3±0.6 | 0.087 |
| Albumin (g/dL) | 4.1±0.5 | 4±0.6 | 0.225 | 4.1±0.5 | 4±0.6 | 0.060 |
| Alanine aminotransferase (U/L) | 31±42.1 | 30.2±58.8 | 0.017 | 30.3±47.2 | 30.3±52.7 | 0.001 |
| Aspartate aminotransferase (U/L) | 26.2±55.1 | 28.1±69.8 | 0.031 | 26.4±64.2 | 27.1±63.2 | 0.011 |
| Alkaline phosphatase (U/L) | 87.8±42.9 | 90±60.3 | 0.042 | 88.3±48.7 | 87.9±50.2 | 0.008 |
| Total bilirubin (mg/dL) | 0.5±0.5 | 0.6±0.7 | 0.103 | 0.6±0.5 | 0.6±0.6 | 0.031 |
| Direct bilirubin (mg/dL) | 0.2±0.6 | 0.3±0.9 | 0.126 | 0.2±0.7 | 0.3±0.8 | 0.042 |
| Hemoglobin (g/dL) | 13.4±1.9 | 12.9±2.2 | 0.252 | 13.3±2 | 13.1±2.1 | 0.092 |
| Triglyceride (mg/dL) | 190±187.2 | 171.1±159.8 | 0.109 | 182.5±162.3 | 181.1±169.1 | 0.008 |
| HDL (mg/dL) | 41.7±15.7 | 42.1±16.5 | 0.026 | 42.2±15.8 | 40.8±17.1 | 0.084 |
| LDL (mg/dL) | 91.2±38.2 | 89.7±36.9 | 0.040 | 88.6±38 | 90.3±38.5 | 0.045 |
| Microalbumin in urine (mg/dL) | 17.3±99.7 | 16.2±74.5 | 0.012 | 18.9±110.4 | 15.8±78.5 | 0.033 |
| Colon and rectum surgery | 11,540 (5) | 6,382 (3.2) | 0.095 | 5,549 (4.4) | 5,547 (4.4) | <0.001 |
| Intestines surgery (except rectum) | 811 (0.4) | 816 (0.4) | 0.008 | 561 (0.4) | 565 (0.4) | <0.001 |
| Biliary tract surgery | 999 (0.4) | 683 (0.3) | 0.016 | 518 (0.4) | 541 (0.4) | 0.003 |
| Stomach surgery | 935 (0.4) | 591 (0.3) | 0.020 | 434 (0.3) | 434 (0.3) | <0.001 |
| Liver surgery | 567 (0.2) | 487 (0.2) | 0.001 | 321 (0.3) | 331 (0.3) | 0.002 |
| Appendix surgery | 298 (0.1) | 144 (0.1) | 0.019 | 119 (0.1) | 129 (0.1) | 0.003 |
| SD – standard deviation; SMD – standardized mean difference; GLP1-RA – glucagon-like peptide-1 receptor agonist; DPP4i – dipeptidyl peptidase-4 inhibitor; RAS – renin angiotensin system; BMI – body mass index; renin-angiotensin system; SGLT2i – sodium-glucose co-transporter-2 inhibitors; eGFR – estimated glomerular filtration rate; HDL – high-density lipoprotein; LDL – low-density lipoprotein. | ||||||