Comparison of cardiovascular and metabolic outcomes in people with type 2 diabetes on insulin versus non-insulin glucose-lowering therapies (GLTs): A systematic review and meta-analysis of clinical trials.
OBJECTIVE
To compare the cardiovascular and metabolic outcomes of Insulin versus non-insulin glucose lowering therapy (GLT).


METHODS
We included randomised control trials (RCTs) which randomised patients aged >18years 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=0.92-2.62). 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: 1.44-2.51) increased risk of hypoglycaemia.


CONCLUSIONS
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. Non-insulin GLTs were associated with a higher risk in reported adverse drug events.
Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, United Kingdom.
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U
Anyanwagu
Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, United Kingdom.
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J
Mamza
Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, United Kingdom.
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R
Donnelly
Division of Medical Sciences & Graduate Entry Medicine, School of Medicine, University of Nottingham, United Kingdom. Electronic address: iidris@aol.com.
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I
Idris
D001835:Body Weight / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000139:chemically induced* / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D038321:Glycemic Index; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012306:Risk; D015996:Survival Rate; D016896:Treatment Outcome
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human
Cardiovascular; Insulin; Meta-analysis; Metabolic; Non-insulin