Effects on All-cause Mortality and Cardiovascular Outcomes in Patients With Type 2 Diabetes by Comparing Insulin With Oral Hypoglycemic Agent Therapy: A Meta-analysis of Randomized Controlled Trials

Purpose Retrospective, case–control studies and prospective randomized controlled trials (RCTs) on insulin treatment for diabetic patients yielded contradictory mortality and cardiovascular outcomes. We aimed to evaluate the effects of insulin versus oral hypoglycemic agents (OHAs) on all-cause mortality and cardiovascular outcomes in patients with type 2 diabetes (T2D). Methods We searched Medline, Embase, Cochrane Central Register of Controlled Trials, Chinese Biological Medicine Database, China National Knowledge Infrastructure, Chinese Technical Periodicals, and Wanfang Data, up to July 10, 2015, for RCTs on insulin and OHAs that assessed all-cause mortality and/or cardiovascular death as primary end points. We derived pooled risk ratios (RRs) as summary statistics. Results Three trials were included in which 7649 patients received insulin and 8322 received OHAs, with mean (SD) diabetes duration of 5.0 (6.2) and 4.4 (5.9) years, respectively. Insulin did not differ from OHAs in all-cause mortality (RR = 1.00; 95% CI, 0.93–1.07), cardiovascular death (RR = 1.00; 95% CI, 0.91–1.09), myocardial infarction (RR = 1.04; 95% CI, 0.93–1.16), angina (RR = 0.97; 95% CI, 0.88–1.06), sudden death (RR = 1.02; 95% CI, 0.66–1.56), or stroke (RR = 1.01; 95% CI, 0.88–1.15). Insulin reduced the risk of heart failure compared with OHAs (RR = 0.87; 95% CI, 0.75–0.99). In the subgroup of secondary prevention of cardiovascular diseases (CVDs) or very high risk of CVDs, insulin did not differ from OHAs in all-cause mortality (RR = 0.99; 95% CI, 0.92–1.07), cardiovascular death (RR = 0.99; 95% CI, 0.90–1.09), myocardial infarction (RR = 1.01; 95% CI, 0.88–1.15), heart failure (RR = 0.69; 95% CI, 0.34–1.40), or stroke (RR = 1.05; 95% CI, 0.90–1.21). Implications Insulin did not provide a clear benefit over OHAs in all-cause mortality or cardiovascular outcomes in the patients with T2D. Insulin therapy has many shortcomings, including inconvenience (injection, strict blood glucose monitoring), hypoglycemia, and obvious weight gain. Thus, we conclude that no robust evidence supports the active use of insulin for this population at present.