All-cause mortality in patients with diabetes under glucagon-like peptide-1 agonists: A population-based, open cohort study.
OBJECTIVE
The glucagon-like peptide-1 receptor agonist (GLP1a) liraglutide has been described to benefit patients with type 2 diabetes mellitus (T2DM) at high cardiovascular risk. However, there are still uncertainties relating to these cardiovascular benefits: whether they also apply to an unselected diabetic population that includes low-risk patients, represent a class-effect, and could be observed in a real-world setting.


METHODS
We conducted a population-based, retrospective open cohort study using data derived from The Health Improvement Network database between Jan 2008 to Sept 2015. Patients with T2DM exposed to GLP1a (n=8345) were compared to age, gender, body mass index, duration of T2DM and smoking status-matched patients with T2DM unexposed to GLP1a (n=16,541).


RESULTS
Patients with diabetes receiving GLP1a were significantly less likely to die from any cause compared to matched control patients with diabetes (adjusted incidence rate ratio [aIRR]: 0.64, 95% CI: 0.56-0.74, P-value<0.0001). Similar findings were observed in low-risk patients (aIRR: 0.64, 95% CI: 0.53-0.76, P -value=0.0001). No significant difference in the risk of incident CVD was detected in the low-risk patients (aIRR: 0.93, 95% CI: 0.83-1.12). Subgroup analyses suggested that effect is persistent in the elderly or across glycated haemoglobin categories.


CONCLUSIONS
GLP1a treatment in a real-world setting may confer additional mortality benefit in patients with T2DM irrespective of their baseline CVD risk, age or baseline glycated haemoglobin and was sustained over the observation period.
Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom; 424 General Military Hospital, Thessaloniki, Greece.
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KA
Toulis
Diabetes Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
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W
Hanif
University of Warwick & George Eliot Hospital, Coventry, United Kingdom.
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P
Saravanan
Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom.
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BH
Willis
Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom.
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T
Marshall
Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom.
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B
Kumarendran
Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom.
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K
Gokhale
Diabetes Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom.
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S
Ghosh
Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom.
K K
KK
Cheng
Diabetes Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom; Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, United Kingdom.
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P
Narendran
Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom. Electronic address: gneilthomas@yahoo.co.uk.
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Thomas
Institute of Applied Health Research, University of Birmingham, Birmingham, United Kingdom; Diabetes Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, United Kingdom. Electronic address: k.nirantharan@bham.ac.uk.
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Nirantharakumar
D000368:Aged; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology / Q000401:mortality; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology / Q000401:mortality; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000819:agonists*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069450:Liraglutide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
D007004:Hypoglycemic Agents; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1
Cardiovascular disease; GLP-1 agonists; Pharmaco-epidemiology; Type 2 diabetes mellitus