Diabetes and cardiovascular disease
Epidemiology
Cardiovascular outcome trials
Strict glycemic control
Multifactorial management
Concerns with glucose-lowering drugs
Potential problem | Pharmacological agent |
---|---|
Weight gain | Sulfonylureas, glinides, TZDs, insulin |
Gastrointestinal | Biguanides, α‑glucosidase inhibitors |
Hypoglycemia | Sulfonylureas, glinides, insulin |
Lactic acidosis | Biguanides |
B12 deficiency | Biguanides |
Kidney dysfunction | Biguanides, sulfonylureas |
Urinary tract infection | SGLT-2 inhibitors |
Bladder cancer | TZDs |
Hepatic dysfunction | Glinides, TZDs, biguanides |
Pancreatitis | DPP-4 inhibitors, GLP-1 agonists |
Fractures | TZDs |
Cardiovascular concerns | TZDs |
Trial [ref.] | Treatment Active/comparator | Patient type (n) | Primary endpoint | Follow-up median (years) | Outcome HR (95% CI), p | Remarks |
---|---|---|---|---|---|---|
PPAR-γ
| ||||||
PROACTIVE [23] | Pioglitazone/placebo | T2DM + macrovascular disease (5238) | A composite of all-cause death, nonfatal MI, stroke, ACS, endovascular or surgical intervention in the coronary or leg arteries, and amputation above the ankle | 2.9 | No difference 0.90 (0.80–1.02); p = 0.095 | Secondary outcome composite of CV death and nonfatal MI or stroke 0.84 (0.72–0.98); p = 0.027 |
Insulin
| ||||||
ORIGIN [52] | Insulin glargine/conventional | T2DM, IFG, IGT + high CV risk (12,537) | Composite of CV death and nonfatal MI or stroke | 6.2 | No difference 1.02 (0.94–1.11); p = 0.63 | – |
DEVOTE [53] | Insulin degludec/insulin glargine | T2DM + CVD, renal disease or high CV risk (7637) | Composite of CV death and nonfatal MI or stroke | 1.9 | No difference 0.91 (0.78–1.06); p < 0.001 | – |
SGLT-2 inhibitors
| ||||||
EMPA-REG Outcome [39] | Empagliflozin/placebo | T2DM + CVD (7020) | Composite of CV death and nonfatal MI or stroke | 3.1 | 0.86 (0.74–0.99); p = 0.0382 | Decrease in heart failure hospitalization 0.65 (0.50–0.85) p = 0.002 |
CANVAS [41] | Canagliflozin/placebo | T2DM + high CV risk (10,142) | Composite of CV death and nonfatal MI or stroke | 2.4 | 0.86 (0.75–0.97) p = 0.02 | Decrease in heart failure hospitalization 0.67 (0.52–0.87) p < 0.001 |
DECLARE-TIMI 58 [43] | Dapagliflozin/placebo | T2DM + CVD or high CV risk (17,160) | Composite of CV death and nonfatal MI or stroke | 4.2 | 0.93 (95% CI, 0.84–1.03) p = 0.17 | – |
DPP-4 inhibitors
| ||||||
TECOS [34] | Sitagliptin/placebo | T2DM + CVD (14,671) | Composite of CV death and nonfatal MI or stroke or hospitalization for UA | 3.0 | No difference 0.98 (0.89–1.08); p = 0.65 | No increase in heart failure |
EXAMINE [35] | Alogliptin/Placebo | T2DM + recent ACS (5380) | Composite of CV death and nonfatal MI or stroke | 1.5 | No difference 0.96 (≤1.16); p = 0.32 | No increase in heart failure |
SAVOR-TIMI 53 [36] | Saxagliptin/placebo | T2DM + CVD or high CV risk (16,492) | Composite of CV death and nonfatal MI or stroke | 2.1 | No difference 1.00 (0.89–1.12); p = 0.99 | Increase in heart failure hospitalizations in the saxagliptin group |
CARMELINA [37] | Linagliptin/placebo | T2DM + high CV or renal risk (6979) | Composite of CV death and nonfatal MI or stroke | 2.2 | No difference 1.02; 95% CI, 0.89–1.17; p < 0.001 | No increase in heart failure |
GLP-1 receptor agonists
| ||||||
LEADER [45] | Liraglutide/placebo | T2DM + CVD or high CV risk (9340) | Composite of CV death and nonfatal MI or stroke | 3.8 | 0.87 (0.78–0.97); p = 0.01 | – |
SUSTAIN-6 [46] | Semaglutide/placebo | T2DM + CVD, renal disease or high CV risk (2735) | Composite of CV death and nonfatal MI or stroke | 1.9 | 0.74 (0.58 to 0.95); p < 0.001 | No increase in heart failure |
HARMONY-OUTCOMES [48] | Albiglutide/placebo | T2DM + CVD (9463) | Composite of CV death and nonfatal MI or stroke | 1.6 | 0.78 (0.68–0.90) p < 0.001 | – |
REWIND | Dulaglutide/placebo | T2DM + CVD or high CV risk (9622) | Composite of CV death and nonfatal MI or stroke | Not available | Not available | – |
ELIXA [50] | Lixisenatide/placebo | T2DM + ACS (6068) | Composite of CV death and nonfatal MI or stroke or hospitalization for UA | 2.1 | No difference 1.02 (0.89–1.17); p = 0.81 | No increase in heart failure |
EXSCEL [49] | Exenatide/placebo | T2DM +/− CVD (14,752) | Composite of CV death and nonfatal MI or stroke or hospitalization for UA | 3.2 | No difference | No increase in heart failure |