Mortality and other important diabetes-related outcomes with insulin vs other antihyperglycemic therapies in type 2 diabetes.
BACKGROUND
The safety of insulin in the treatment of type 2 diabetes mellitus (T2DM) has recently undergone scrutiny.


OBJECTIVE
The objective of the study was to characterize the risk of adverse events associated with glucose-lowering therapies in people with T2DM.


METHODS
This was a retrospective cohort study using data from the UK General Practice Research Database, 2000-2010.


METHODS
Patients comprised 84 622 primary care patients with T2DM treated with one of five glucose-lowering regimens: metformin monotherapy, sulfonylurea monotherapy, insulin monotherapy, metformin plus sulfonylurea combination therapy, and insulin plus metformin combination therapy. There were 105 123 exposure periods.


METHODS
The risk of the first major adverse cardiac event, first cancer, or mortality was measured. Secondary outcomes included these individual constituents and microvascular complications.


RESULTS
In the same model, and using metformin monotherapy as the referent, the adjusted hazard ratio (aHR) for the primary end point was significantly increased for sulfonylurea monotherapy (1.436, 95% confidence interval [CI] 1.354-1.523), insulin monotherapy (1.808, 95% CI 1.630-2.005), and insulin plus metformin (1.309, 95% CI 1.150-1.491). In glycosylated hemoglobin/morbidity subgroups, patients treated with insulin monotherapy had aHRs for the primary outcome ranging from 1.469 (95% CI 0.978-2.206) to 2.644 (95% CI 1.896-3.687). For all secondary outcomes, insulin monotherapy had increased aHRs: myocardial infarction (1.954, 95% CI 1.479-2.583), major adverse cardiac events (1.736, 95% CI 1.441-2.092), stroke (1.432, 95% CI 1.159-1.771), renal complications (3.504, 95% CI 2.718-4.518), neuropathy (2.146, 95% CI 1.832-2.514), eye complications (1.171, 95% CI 1.057-1.298), cancer (1.437, 95% CI 1.234-1.674), or all-cause mortality (2.197, 95% CI 1.983-2.434). When compared directly, aHRs were higher for insulin monotherapy vs all other regimens for the primary end point and all-cause mortality.


CONCLUSIONS
In people with T2DM, exogenous insulin therapy was associated with an increased risk of diabetes-related complications, cancer, and all-cause mortality. Differences in baseline characteristics between treatment groups should be considered when interpreting these results.
School of Medicine, Cardiff University, The Pharma Research Centre, Cardiff MediCentre, Cardiff CF14 4UJ, United Kingdom. currie@cardiff.ac.uk
Craig J
CJ
Currie
Chris D
CD
Poole
Marc
M
Evans
John R
JR
Peters
Christopher Ll
CL
Morgan
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000401:mortality*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use*; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012306:Risk; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D016896:Treatment Outcome
D007004:Hypoglycemic Agents; D007328:Insulin; D013453:Sulfonylurea Compounds; D008687:Metformin