Objectives: To compare the cardiovascular and metabolic outcomes of Insulin versus noninsulin glucose lowering therapy (GLT).Methods: We included randomised control trials (RCTs) which randomised patients aged >18 years with Type 2 Diabetes (T2D) to insulin vs non-insulin GLT. We used risk ratios (RR), risk difference (RD) and odds ratios (OR) with 95% confidence interval (95%CI) to analyse the treatment effects of dichotomous outcomes and mean differences (with 95% CI) for continuous outcomes.Results: We included 18 RCTs with 19,300 participants. There was no significant difference in the risk of all-cause mortality and CV events between the groups (RR= 1.01; 95%CI: 0.96 -1.06; p = 0.69). In 16 trials, insulin showed greater efficacy in glycaemic control (mean diff= -0.20; 95%CI: -0.28 to -0.11 but the proportion achieving HbA1c level of either ≤7.0% or 7.4% (53 or 57mmol/mol) was similar in both (OR=1.55; 95%CI= 0.92 to 2.62). The non-insulin group had a significant reduction in weight (mean diff = -3.41; 95%CI: -4.50 to -2.32) and an increase in the proportion of adverse events (54.7% vs 45.3%, p= 0.044), but the insulin group showed an (RR= 1.90; 95%CI: 1.44 to 2.51) increased risk of hypoglycaemia.Conclusion: There was no difference in the risk of all-cause mortality and adverse cardiovascular (CV) events between Insulin and non-insulin GLTs. Insulin was associated with superior reduction in HbA1c; least reduction in weight and higher risk of hypoglycaemia. Both showed similar proportion of patients achieving HbA1c target. Noninsulin GLTs were associated with a higher risk in reported adverse drug events.3 | P a g e
Introduction:For many patients with type 2 diabetes (T2D), treatment intensification using additional antihyperglycaemic agents is required in order to achieve optimal glycaemic control and prevent long-term vascular complications.[1, 2] A variety of antihyperglycaemic agents are available but questions regarding the long term safety and efficacy of some of these agents have been raised. In addition, recent focus by international regulatory agencies on the cardiovascular (CV) safety profile of commonly used antihyperglycaemic agents [3,4] have led to debate about the most appropriate choice of therapy for treatment intensification.Amidst this, exogenous insulin remains to be one of the most established glucose lowering therapies available [5][6][7][8][9][10] and its use in people with T2D has grown markedly over recent years. More recently however, the effectiveness and safety of insulin therapy has been a subject of intense discussion.[11-13] Moreover, recent large epidemiological studies have reported adverse cardiovascular CV outcome and increase mortality with insulin compared with non-insulin therapy. [13, 14] While the possible mechanism behind the observed the association between insulin and adverse cardiovascular and metabolic outcomes and mortality remains unclear, it is hypothesized that these may include, but not limited to, hypoglycaemia and weight gain. Although insulin the...