Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review and Network Meta-analysis for the American College of PhysiciansFREE
Submit a Comment
Contributors must reveal any conflict of interest. Comments are moderated. Please see our information for authorsregarding comments on an Annals publication.
Abstract
Background:
Purpose:
Data Sources:
Study Selection:
Data Extraction:
Data Synthesis:
Limitations:
Conclusion:
Primary Funding Source:
Methods
Data Sources and Searches
Study Selection
Data Abstraction and Quality Assessment
Data Synthesis and Analysis
Comparison | Trials, k; Participants, n RR (95% CI) Absolute Risk Difference per 1000 Persons (95% CI)* Certainty of Evidence† | |||||||
---|---|---|---|---|---|---|---|---|
All-Cause Mortality | MACE | MI | Stroke | CHF Hospitalization | CKD Stage 3+ | Serious Adverse Event | Severe Hypoglycemia | |
Compared with placebo or usual care | ||||||||
DPP4 inhibitors | k = 10; n = 47 577 RR, 1.01 (0.94 to 1.08)‡ 1 more (4 fewer to 5 more) ⊕⊕⊕ | k = 5; n = 44 595 RR, 1.0 (0.94 to 1.06)‡ 0 fewer (6 fewer to 6 more) ⊕⊕⊕ | k = 2; n = 31 015 RR, 0.95 (0.85 to 1.06)‡ 2 fewer (6 fewer to 2 more) ⊕⊕⊕ | k = 1; n = 14 523 RR, 0.97 (0.79 to 1.19)‡ 1 fewer (5 fewer to 5 more) ⊕⊕⊕ | k = 3; n = 37 994 RR, 1.06 (0.96 to 1.17)‡ 2 more (1 fewer to 6 more) ⊕⊕⊕ | k = 2; n = 23 477 RR, 1.07 (0.95 to 1.21)‡ 3 more (2 fewer to 9 more) ⊕⊕⊕ | k = 9; n = 26 256 RR, 0.96 (0.92 to 1.01)‡ 8 fewer (15 fewer to 2 more) ⊕⊕⊕ | k = 9; n = 47 160 RR, 1.14 (1.00 to 1.30)‡ 2 more (0 fewer to 5 more) ⊕⊕⊕ |
GLP1 agonists | k = 8; n = 48 481 RR, 0.88 (0.83 to 0.94)‡ 10 fewer (14 fewer to 5 fewer) ⊕⊕⊕ | k = 6; n = 46 541 RR, 0.91 (0.87 to 0.96)‡ 11 fewer (16 fewer to 5 fewer) ⊕⊕⊕ | k = 5; n = 43 244 RR, 0.96 (0.89 to 1.04)‡ 3 fewer (7 fewer to 3 more) ⊕⊕⊕ | k = 5; n = 43 244 RR, 0.86 (0.77 to 0.95)‡ 5 fewer (7 fewer to 2 fewer) ⊕⊕⊕ | k = 4; n = 33 904 RR, 0.95 (0.85 to 1.06)‡ 2 fewer (5 fewer to 2 more) ⊕⊕⊕ | GLP1 agonists not in network | k = 8; n = 36 188 RR, 0.98 (0.95 to 1.01)‡ 5 fewer (13 fewer to 3 more) ⊕⊕⊕ | k = 8; n = 42 250 RR, 1.02 (0.92 to 1.15)‡ 0 fewer (2 fewer to 3 more) ⊕⊕◯§ |
SGLT2 inhibitors | k = 14; n = 47 478 RR, 0.86 (0.80 to 0.93)‡ 9 fewer (13 fewer to 5 fewer) ⊕⊕⊕ | k = 3; n = 19 659 RR, 0.90 (0.83 to 0.98)‡ 12 fewer (21 fewer to 2 fewer) ⊕⊕◯§ | k = 2; n = 15 266 RR, 0.97 (0.85 to 1.12)‡ 2 fewer (8 fewer to 7 more) ⊕⊕⊕ | k = 2; n = 15 266 RR, 1.12 (0.93 to 1.34)‡ 4 more (2 fewer to 10 more) ⊕⊕⊕ | k = 2; n = 11 421 RR, 0.64 (0.54 to 0.77)‡ 19 fewer (24 fewer to 12 fewer) ⊕⊕⊕ | k = 4; n = 32 713 RR, 0.66 (0.58 to 0.75)‡ 12 fewer (14 fewer to 9 fewer) ⊕⊕⊕ | k = 14; n = 46 096 RR, 0.93 (0.90 to 0.95)‡ 23 fewer (33 fewer to 16 fewer) ⊕⊕⊕ | k = 9; n = 39 902 RR, 0.85 (0.74 to 0.97)‡ 3 fewer (5 fewer to 1 fewer) ⊕⊕⊕ |
Tirzepatide | NMA RR, 0.98 (0.56 to 1.73) ⊕◯◯‖¶** | ◯◯◯†† | Tirzepatide not in network | Tirzepatide not in network | Tirzepatide not in network | Tirzepatide not in network | k = 3; n = 1069 RR, 0.79 (0.51 to 1.22)‡ 17 fewer (39 fewer to 17 more) ⊕⊕⊕ | k = 3; n = 1373 RR, 1.32 (0.78 to 2.22)‡ 15 more (10 fewer to 55 more) ⊕⊕◯¶ |
Basal insulin | NMA RR, 1.23 (0.89 to 1.70) ⊕◯◯‖¶** | NMA RR, 1.10 (0.83 to 1.46) ⊕◯◯‖¶** | Basal insulin not in network | Basal insulin not in network | NMA RR, 1.01 (0.64 to 1.60) ⊕◯◯‖¶** | Basal insulin not in network | NMA RR, 1.17 (0.99 to 1.39) ⊕⊕◯‖** | NMA RR, 3.81 (2.70 to 5.38) ◯◯◯‖‡‡** |
DPP4 inhibitors (head-to-head) | ||||||||
DPP4 inhibitors vs. GLP1 agonists | k = 4; n = 4612 RR, 1.64 (1.05 to 2.56)‡ 7 more (1 more to 14 more) ⊕⊕◯§§ | k = 1; n = 2515 RR, 1.42 (0.99 to 2.04)‡ 16 more (0 fewer to 40 more) ⊕⊕⊕ | NMA RR, 0.98 (0.86 to 1.13) ⊕⊕◯‖** | NMA RR, 1.14 (0.90 to 1.43) ⊕⊕◯‖** | k = 1; n = 2515 RR, 2.12 (1.13 to 3.98)‡ 13 more (1 more to 33 more) ⊕⊕◯¶ | GLP1 agonists not in network | k = 5; n = 5168 RR, 1.07 (0.89 to 1.29)‡ 6 more (10 fewer to 26 more) ⊕⊕⊕ | k = 4; n = 6724 RR, 1.25 (0.91 to 1.73)‡ 7 more (2 fewer to 20 more) ⊕⊕⊕ |
DPP4 inhibitors vs. basal insulin | k = 1; n = 2531 RR, 0.97 (0.64 to 1.48)‡ 1 fewer (12 fewer to 16 more) ⊕⊕⊕ | k = 1; n = 2521 RR, 1.06 (0.76 to 1.47)‡ 3 more (12 fewer to 24 more) ⊕⊕⊕ | Basal insulin not in network | Basal insulin not in network | k = 1; n = 2521 RR, 1.15 (0.68 to 1.93)‡ 3 more (7 fewer to 19 more) ⊕⊕⊕ | Basal insulin not in network | NMA RR, 0.82 (0.68 to 0.97) ⊕◯◯§§‖** | k = 1; n = 2531 RR, 0.56 (0.25 to 1.26)‡ 6 fewer (10 fewer to 3 more) ⊕⊕◯¶ |
DPP4 inhibitors vs. SGLT2 inhibitors | k = 5; n = 3878 RR, 1.20 (0.32 to 4.48)‡ 0 fewer (2 fewer to 8 more) ⊕◯◯‡‡ | NMA RR, 1.13 (1.03 to 1.25) ⊕⊕◯‖** | NMA RR, 0.98 (0.82 to 1.17) ⊕⊕◯‖** | NMA RR, 0.87 (0.66 to 1.15) ⊕⊕◯‖** | NMA RR, 1.68 (1.36 to 2.07) ⊕◯◯‖¶** | NMA RR, 1.62 (1.36 to 1.94) ⊕⊕◯‖** | k = 4; n = 3455 RR, 0.99 (0.75 to 1.31)‡ 1 fewer (14 fewer to 17 more) ⊕⊕⊕ | k = 4; n = 3105 RR, 0.78 (0.10 to 5.99)‡ 0 fewer (2 fewer to 10 more) ⊕◯◯‡‡ |
DPP4 inhibitors vs. sulfonylurea | k = 10; n = 22 352 RR, 0.90 (0.79 to 1.03)‡ 4 fewer (8 fewer to 1 more) ⊕⊕⊕ | k = 4; n = 12 715 RR, 0.96 (0.85 to 1.09)‡ 3 fewer (12 fewer to 7 more) ⊕⊕⊕ | k = 1; n = 6033 RR, 1.03 (0.83 to 1.28)‡ 1 more (8 fewer to 14 more) ⊕⊕⊕ | k = 1; n = 6033 RR, 0.86 (0.67 to 1.12)‡ 6 fewer (13 fewer to 5 more) ⊕⊕⊕ | k = 2; n = 8544 RR, 1.16 (0.91 to 1.47)‡ 5 more (3 fewer to 13 more) ⊕⊕⊕ | Sulfonylurea not in network | k = 10; n = 20 439 RR, 0.95 (0.91 to 0.99)‡ 12 fewer (21 fewer to 2 fewer) ⊕⊕◯¶ | k = 8; n = 18 081 RR, 0.14 (0.11 to 0.19)‡ 44 fewer (46 fewer to 42 fewer) ⊕⊕⊕ |
DPP4 inhibitors vs. tirzepatide | NMA RR, 1.04 (0.59 to 1.83) ⊕◯◯‖¶** | NMA RR, 1.21 (0.76 to 1.92) ⊕◯◯‖¶** | Tirzepatide not in network | Tirzepatide not in network | Tirzepatide not in network | Tirzepatide not in network | NMA RR, 0.99 (0.80 to 1.22) ⊕⊕◯‖** | NMA RR, 1.03 (0.68 to 1.57) ◯◯◯‖‡‡** |
GLP1 agonists (head-to-head) | ||||||||
GLP1 agonists vs. DPP4 inhibitors | k = 4; n = 4612 RR, 0.61 (0.39 to 0.95)‡ 9 fewer (14 fewer to 1 fewer) ⊕⊕◯§§ | k = 1; n = 2515 RR, 0.70 (0.49 to 1.01)‡ 16 fewer (28 fewer to 1 more) ⊕⊕⊕ | NMA RR, 1.02 (0.88 to 1.16) ⊕⊕◯‖** | NMA RR, 0.88 (0.70 to 1.11) ⊕⊕◯‖** | k = 1; n = 2515 RR, 0.47 (0.25 to 0.88)‡ 13 fewer (18 fewer to 3 fewer) ⊕⊕◯¶ | GLP1 agonists not in network | k = 5; n = 5168 RR, 0.94 (0.78 to 1.13)‡ 5 fewer (20 fewer to 12 more) ⊕⊕⊕ | k = 4; n = 6724 RR, 0.81 (0.59 to 1.11)‡ 4 fewer (9 fewer to 2 more) ⊕⊕⊕ |
GLP1 agonists vs. basal insulin | k = 4; n = 4792 RR, 0.62 (0.41 to 0.93)‡ 10 fewer (16 fewer to 2 fewer) ⊕⊕◯¶ | k = 1; n = 2508 RR, 0.74 (0.52 to 1.07)‡ 13 fewer (25 fewer to 4 more) ⊕⊕⊕ | Basal insulin not in network | Basal insulin not in network | k = 1; n = 2508 RR, 0.54 (0.28 to 1.03)‡ 10 fewer (15 fewer to 1 more) ⊕⊕◯¶ | GLP1 agonists and basal insulin not in network | k = 5; n = 3579 RR, 0.86 (0.72 to 1.04) 16 fewer (33 fewer to 5 more) ⊕◯◯§¶ | k = 6; n = 6104 RR, 0.23 (0.16 to 0.33) 38 fewer (42 fewer to 33 fewer) ⊕⊕◯¶‖‖ |
GLP1 agonists vs. SGLT2 inhibitors | NMA RR, 1.02 (0.93 to 1.12) ⊕⊕◯‖** | NMA RR, 1.01 (0.92 to 1.11) ⊕⊕◯‖** | NMA RR, 0.99 (0.85 to 1.16) ⊕⊕◯‖** | NMA RR, 0.77 (0.62 to 0.95) ⊕⊕◯‖** | NMA RR, 1.44 (1.16 to 1.78) ⊕⊕◯‖** | GLP1 agonists not in network | k = 2; n = 1249 RR, 0.93 (0.60 to 1.45)‡ 4 fewer (25 fewer to 28 more) ⊕⊕◯¶ | k = 3; n = 2068 RR, 1.00 (0.47 to 2.14)‡ 0 fewer (7 fewer to 14 more) ⊕⊕◯¶ |
GLP1 agonists vs. sulfonylurea | k = 3; n = 4281 RR, 0.67 (0.44 to 1.04)‡ 8 fewer (13 fewer to 10 more) ⊕⊕⊕ | k = 1; n = 2498 RR, 0.81 (0.56 to 1.18)‡ 9 fewer (21 fewer to 9 more) ⊕⊕⊕ | ◯◯◯†† | ◯◯◯†† | k = 1; n = 2498 RR, 0.47 (0.25 to 0.87)‡ 13 fewer (18 fewer to 3 fewer) ⊕⊕◯¶ | GLP1 agonists and sulfonylurea not in network | k = 2; n = 1765 RR, 1.08 (0.83 to 1.41)‡ 9 more (20 fewer to 48 more) ⊕⊕◯¶ | k = 3; n = 4281 RR, 0.49 (0.26 to 0.92)‡ 7 fewer (10 fewer to 1 fewer) ⊕⊕◯¶ |
GLP1 agonists vs. tirzepatide | k = 1; n = 1878 RR, 0.25 (0.03 to 1.92)‡ 6 fewer (8 fewer to 8 more) ⊕◯◯¶¶ | NMA RR, 1.08 (0.68 to 1.73) ⊕◯◯‖¶** | Tirzepatide not in network | Tirzepatide not in network | Tirzepatide not in network | GLP1 agonists and tirzepatide not in network | k = 2; n = 2143 RR, 0.57 (0.34 to 0.96)‡ 24 fewer (37 fewer to 2 fewer) ⊕⊕◯§ | k = 2; n = 2143 RR, 0.50 (0.11 to 2.23)‡ 4 fewer (7 fewer to 9 more) ⊕◯◯‡‡ |
SGLT2 inhibitors (head-to-head) | ||||||||
SGLT2 inhibitors vs. DPP4 inhibitors | k = 5; n = 3878 RR, 0.91 (0.3 to 2.78)‡ 0 fewer (1 fewer to 4 more) ⊕◯◯‡‡ | NMA RR, 0.88 (0.80 to 0.97) ⊕⊕◯‖** | NMA RR, 1.02 (0.85 to 1.22) ⊕⊕◯‖** | NMA RR, 1.15 (0.87 to 1.52) ⊕⊕◯‖** | NMA RR, 0.60 (0.48 to 0.74) ⊕◯◯‖¶** | NMA RR, 0.62 (0.52 to 0.74) ⊕⊕◯‖** | k = 5; n = 3878 RR, 1.01 (0.76 to 1.32)‡ 1 more (13 fewer to 17 more) ⊕⊕⊕ | k = 4; n = 3105 RR, 1.42 (0.26 to 7.59)‡ 0 fewer (1 fewer to 6 more) ⊕◯◯‡‡ |
SGLT2 inhibitors vs. GLP1 agonists | NMA RR, 0.98 (0.89 to 1.08) ⊕⊕◯‖** | NMA RR, 0.99 (0.90 to 1.09) ⊕⊕◯‖** | NMA RR, 1.01 (0.86 to 1.18) ⊕⊕◯‖** | NMA RR, 1.30 (1.05 to 1.61) ⊕⊕◯‖** | NMA RR, 0.69 (0.56 to 0.86) ⊕⊕◯‖** | GLP1 agonists not in network | k = 2; n = 1249 RR, 1.08 (0.83 to 1.41)‡ 5 more (10 fewer to 24 more) ⊕⊕◯¶ | k = 3; n = 2068 RR, 1.00 (0.47 to 2.14)‡ 0 fewer (7 fewer to 14 more) ⊕⊕◯¶ |
SGLT2 inhibitors vs. basal insulin | NMA RR, 0.70 (0.51 to 0.98) ⊕◯◯‖¶** | NMA RR, 0.81 (0.61 to 1.09) ⊕◯◯‖¶** | Basal insulin not in network | Basal insulin not in network | NMA RR, 0.64 (0.39 to 1.04) ⊕◯◯‖¶** | Basal insulin not in network | NMA RR, 0.79 (0.67 to 0.94) ⊕◯◯§§‖** | NMA RR, 0.22 (0.15 to 0.32) ⊕◯◯§§‖** |
SGLT2 inhibitors vs. sulfonylurea | k = 4; n = 5134 RR, 1.09 (0.55 to 2.20)‡ 1 more (3 fewer to 9 more) ⊕⊕◯¶ | k = 2; n = 2995 RR, 0.57 (0.36 to 0.91)‡ 14 fewer (21 fewer to 3 fewer) ⊕⊕⊕ | ◯◯◯†† | ◯◯◯†† | k = 1; n = 625 RR, 0.33 (0.01 to 8.13)‡ 2 fewer (3 fewer to 23 more) ⊕◯◯‡‡ | Sulfonylurea not in network | k = 5; n = 5560 RR, 0.99 (0.87 to 1.14)‡ 0 fewer (20 fewer to 21 more) ⊕⊕⊕ | k = 5; n = 5744 RR, 0.10 (0.07 to 0.15)‡ 83 fewer (86 fewer to 79 fewer) ⊕⊕⊕‖‖ |
Remaining comparisons | ||||||||
Sulfonylurea vs. tirzepatide | NMA RR, 1.14 (0.64 to 2.02) ◯◯◯‖‡‡** | NMA RR, 1.30 (0.81 to 2.07) ◯◯◯‖‡‡** | Tirzepatide not in network | Tirzepatide not in network | Tirzepatide not in network | Tirzepatide not in network | NMA RR, 1.03 (0.83 to 1.28) ⊕◯◯§§‖** | NMA RR, 6.72 (4.25 to 10.62) ◯◯◯‖‡‡** |
Tirzepatide vs. sulfonylurea | NMA RR, 0.88 (0.50 to 1.56) ◯◯◯‖‡‡** | NMA RR, 0.77 (0.48 to 1.23) ◯◯◯‖‡‡** | Tirzepatide not in network | Tirzepatide not in network | Tirzepatide not in network | Tirzepatide not in network | NMA RR, 0.97 (0.78 to 1.20) ⊕◯◯§§‖** | NMA RR, 0.15 (0.09 to 0.24) ◯◯◯‖‡‡** |
Basal insulin vs. tirzepatide | k = 2; n = 3432 RR, 1.35 (0.82 to 2.21)‡ 5 more (3 fewer to 17 more) ⊕⊕⊕ | k = 1; n = 1995 RR, 1.31 (0.91 to 1.90)‡ 15 more (4 fewer to 43 more) ⊕⊕⊕ | Basal insulin and tirzepatide not in network | Basal insulin and tirzepatide not in network | Tirzepatide not in network | Basal insulin and tirzepatide not in network | k = 2; n = 3432 RR, 1.26 (1.05 to 1.51) 27 more (5 more to 54 more) ⊕◯◯§¶ | k = 1; n = 1437 RR, 4.86 (2.64 to 8.96)‡ 57 more (24 more to 118 more) ⊕⊕◯¶ |
Tirzepatide vs. basal insulin | k = 2; n = 3432 RR, 0.74 (0.45 to 1.22)‡ 7 fewer (15 fewer to 6 more) ⊕⊕⊕ | k = 1; n = 1995 RR, 0.76 (0.53 to 1.10)‡ 15 fewer (29 fewer to 6 more) ⊕⊕⊕ | Basal insulin and tirzepatide not in network | Basal insulin and tirzepatide not in network | Tirzepatide not in network | Basal insulin and tirzepatide not in network | k = 2; n = 3432 RR, 0.80 (0.67 to 0.96) 32 fewer (52 fewer to 6 fewer) ⊕◯◯§¶ | k = 1; n = 1437 RR, 0.21 (0.11 to 0.38)‡ 57 fewer (64 fewer to 45 fewer) ⊕⊕◯¶ |
Basal insulin vs. SGLT2 inhibitors | NMA RR, 1.42 (1.02 to 1.98) ⊕◯◯‖¶** | NMA RR, 1.23 (0.92 to 1.65) ⊕◯◯‖¶** | Basal insulin not in network | Basal insulin not in network | NMA RR, 1.57 (0.96 to 2.58) ⊕◯◯‖¶** | Basal insulin not in network | NMA RR, 1.26 (1.06 to 1.50) ⊕◯◯§§‖** | NMA RR, 4.51 (3.13 to 6.49) ⊕◯◯§§‖** |
Basal insulin vs. sulfonylurea | k = 1; n = 2517 RR, 0.97 (0.64 to 1.14)‡ 1 fewer (12 fewer to 16 more) ⊕⊕⊕ | k = 1; n = 2504 RR, 1.09 (0.78 to 1.54)‡ 4 more (10 fewer to 26 more) ⊕⊕⊕ | Basal insulin not in network | Basal insulin not in network | k = 1; n = 2504 RR, 0.86 (0.51 to 1.45)‡ 3 fewer (12 fewer to 11 more) ⊕⊕⊕ | Basal insulin not in network | NMA RR, 1.18 (0.99 to 1.41) ⊕◯◯§§‖** | k = 1; n = 2517 RR, 0.57 (0.31 to 1.04)‡ 10 fewer (15 fewer to 1 more) ⊕⊕◯¶ |
SGLT2 inhibitors vs. tirzepatide | ◯◯◯†† | ◯◯◯†† | Tirzepatide not in network | Tirzepatide not in network | Tirzepatide not in network | Tirzepatide not in network | NMA RR, 0.96 (0.78 to 1.19) ⊕◯◯§§‖** | NMA RR, 0.76 (0.50 to 1.17) ⊕◯◯‖¶** |
Role of the Funding Source
Results
Overview


Mortality and Vascular Outcomes
All-Cause Mortality
Major Adverse Cardiovascular Events
Myocardial Infarction
Stroke
CHF Hospitalizations
Chronic Kidney Disease
Serious Adverse Events
Severe Hypoglycemia
Weight Loss
Glycemic Control
Treatment Effects According to Participant Characteristics
Patient Values and Preferences
Discussion
Supplemental Material
- Download
- 1.50 MB
- Download
- 5.17 MB
References
Comments
Sign In to Submit A CommentInformation & Authors
Information
Published In

History
Keywords
Copyright
Authors
Metrics & Citations
Metrics
Citations
If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. For an editable text file, please select Medlars format which will download as a .txt file. Simply select your manager software from the list below and click Download.
For more information or tips please see 'Downloading to a citation manager' in the Help menu.
Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review and Network Meta-analysis for the American College of Physicians. Ann Intern Med.2024;177:618-632. [Epub 19 April 2024]. doi:10.7326/M23-1490
View More
Login Options:
Purchase
You will be redirected to acponline.org to sign-in to Annals to complete your purchase.
Access to EPUBs and PDFs for FREE Annals content requires users to be registered and logged in. A subscription is not required. You can create a free account below or from the following link. You will be redirected to acponline.org to create an account that will provide access to Annals. If you are accessing the Free Annals content via your institution's access, registration is not required.
Create your Free Account
You will be redirected to acponline.org to create an account that will provide access to Annals.
Lifestyle Changes among Adults with Type 2 Diabetes
We read with great interest the systematic review and network meta-analysis from Drake and colleagues (1) for the American College of Physicians which reported a significant reduction in all-cause mortality and major adverse cardiovascular events associated with sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) agonists (but not dipeptidyl peptidase-4 (DPP4) inhibitors, insulin, or tirzepatide) among adults with type 2 diabetes mellitus (T2DM). Importantly, SGLT2 inhibitors and GLP1 agonists were also associated with a reduction in weight and fewer serious adverse effects or hypoglycemic events than other pharmacological treatments (DPP4 inhibitors, sulfonylurea, and insulin). This review confirms previous findings (2) and informs clinical guidelines on treatment of T2DM. The authors should be lauded for conducting an excellent meta-analysis and for the scientific rigor with which they examined these important pharmacologic treatments for adults with T2DM. Unfortunately, however, this review does not discuss or contextualize the first-line therapy and cornerstone of management of type 2 diabetes— lifestyle changes (primarily diet and exercise) (3, 4). The health benefits associated with lifestyle changes for the prevention and management of T2DM are canonical (5). Indeed, there is no single intervention with greater efficacy than lifestyle changes to reduce the risk of virtually all chronic diseases (including T2DM) and major adverse cardiovascular events. In this context, readers should be reminded of the profound benefits associated with lifestyle changes for both all-cause mortality and major adverse cardiovascular events. Lifestyle changes and nondrug therapy represent first-line therapeutics in the armamentarium against T2DM. Additionally, emerging evidence suggests there may be important and synergistic interaction associated with these pharmacologic treatments (SGLT2 inhibitors and GLP1 agonists) and exercise. Better understanding these potential drug-exercise-interactions represents a key opportunity for future investigations.
References
1. Drake T, Landsteiner A, Langsetmo L, MacDonald R, Anthony M, Kalinowski C, et al. Newer Pharmacologic Treatments in Adults With Type 2 Diabetes: A Systematic Review and Network Meta-analysis for the American College of Physicians. Ann Intern Med. 2024.
2. Tsapas A, Avgerinos I, Karagiannis T, Malandris K, Manolopoulos A, Andreadis P, et al. Comparative Effectiveness of Glucose-Lowering Drugs for Type 2 Diabetes: A Systematic Review and Network Meta-analysis. Ann Intern Med. 2020;173(4):278-86.
3. Vijan S. Type 2 Diabetes. Ann Intern Med. 2019;171(9):ITC65-ITC80.
4. Kanaley JA, Colberg SR, Corcoran MH, Malin SK, Rodriguez NR, Crespo CJ, et al. Exercise/Physical Activity in Individuals with Type 2 Diabetes: A Consensus Statement from the American College of Sports Medicine. Med Sci Sports Exerc. 2022;54(2):353-68.
5. Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346(6):393-403.