Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the Diabetes Mellitus Insulin–Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Study

Abstract

Aims/hypothesis This post hoc analysis from the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 trial reports on extended long-term outcome in relation to glucose-lowering agents in patients with myocardial infarction and type 2 diabetes. Methods Patients were randomised as follows: group 1, insulin-based treatment; group 2, insulin during hospitalisation followed by conventional glucose control; and group 3, conventional treatment. Treatment according to the above protocol lasted 2.1 years. Using the total DIGAMI 2 cohort as an epidemiological database, this study presents mortality rates in the randomised groups, and mortality and morbidity rates by glucose-lowering treatment during an extended period of follow-up (median 4.1 and max 8.1 years). Results Follow-up data were available in 1,145 of the 1,253 patients. The mortality rate was 31% (72% cardiovascular) without significant differences between treatment groups. The total number of fatal malignancies was 37, with a trend towards a higher risk in group 1. The HR for death from malignant disease, compared with group 2, was 1.77 (95% CI 0.87-3.61; p=0.11) and 3.60 (95% CI 1.24-10.50; p=0.02) compared with group 3. Insulin treatment was associated with non-fatal cardiovascular events (OR 1.89 95% CI 1.35-2.63; p=0.0002), but not with mortality (OR 1.30, 95% CI 0.93-1.81; p=0.13). Metformin was associated with a lower mortality rate (HR 0.65, 95% CI 0.47-0.90; p=0.01) and a lower risk of death from malignancies (HR 0.25, 95% CI 0.08-0.83; p=0.02). Conclusions/interpretation Patients with type 2 diabetes and myocardial infarction have a poor prognosis. Glucoselowering drugs appear to be of prognostic importance. Insulin may be associated with an increased risk of nonfatal cardiac events, while metformin seems to be protective against risk of death.

Mortality after percutaneous coronary revascularization: Prior cardiovascular risk factor control and improved outcomes in patients with diabetes mellitus

“…In fact, previous authors have shown that insulin use may increase the risk of mortality 33. These findings allied to the risk of hypoglycemia 34 and suggestions that insulin might promote cardiovascular disease or cancers 35, 36, 37 have raised concerns regarding the safety of insulin for type 2 diabetes. However, conflicting evidence from an extended follow‐up of the trial with the biggest between‐group difference in insulin use revealed a 15% reduction in myocardial infarction and a 13% reduction in death among people with new‐onset type 2 diabetes 38.…”

Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia

“…Evidence that metformin is cardioprotective 14,15,28 raises the possibility that any cardiovascular harm of insulin may have been mitigated by metformin. However, any benefit of metformin would have also applied to the 60% of the standard-care group who used metformin.…”

“…7 In addition, one trial showed increased mortality. 10 These findings, the risk of hypoglycemia, 11 and suggestions that insulin might promote cardiovascular disease or cancers [12][13][14] have raised concerns regarding the safety of insulin for type 2 diabetes. Conversely, extended follow-up of the trial with the biggest between-group difference in insulin use until now (the United Kingdom Prospective Diabetes Study [UKPDS]) revealed a 15% reduction in myocardial infarction and a 13% reduction in death among people with new-onset type 2 diabetes.…”

The Michigan Model for Coronary Heart Disease in Type 2 Diabetes: Development and Validation

“…Transition probabilities for the CHD submodel were developed using PubMed searches to identify prospective observational studies and clinical trials [39][40][41][42][43][44][45][46][47] that described various stages of CHD in patients with T2DM. Transition probabilities and references are reported in Supplementary Tables S1 and S2.…”

“…We used 21 outcomes and complications from six published cohort studies and randomized trials [40][41][42][44][45][46] using the new, stand-alone, CHD submodel. No other submodels from the MMD were implemented during the internal validation.…”