Three-year mortality in diabetic patients treated with different combinations of insulin secretagogues and metformin.
BACKGROUND
Several studies have shown an increase of mortality in diabetic patients treated with combinations of sulphonylureas and biguanides. Comparisons between different insulin secretagogues in combination with metformin with respect to all-cause mortality have not been reported so far.


METHODS
An observational cohort study was performed on a consecutive series of 2002 outpatients with type 2 diabetes mellitus. Of these patients, 696 (34.8%) were receiving combinations of insulin secretagogues and biguanides at enrollment. Three-year mortality was assessed through research in the City of Florence Registry Office.


RESULTS
During follow-up, 295 deaths were recorded. Among patients on combined secretagogue and biguanide treatment, glibenclamide was associated with a significantly higher yearly mortality (8.7%) than repaglinide (3.1%; p = 0.002), gliclazide (2.1%; p = 0.001), and glimepiride (0.4%; p < 0.0001). After adjusting for potential confounders (including age; duration of diabetes; Body Mass Index (BMI); lipid profile; HbA(1c); insulin treatment; metformin doses; Charlson co-morbidity score; CCS), mortality remained significantly higher in patients treated with combinations of glibenclamide and metformin when compared to those treated with different insulin secretagogues (OR with 95% CI: 2.09 [1.07;4.11]).


CONCLUSIONS
In the present study, sulphonylureas with greater selectivity for beta-cell receptors, such as glimepiride and gliclazide, were associated with a lower mortality when used in combination with metformin in comparison with glibenclamide. Safety of such combinations deserves further investigation.
Monami
Matteo
M
Department of Critical Care Medicine and Surgery, Unit of Gerontology and Geriatrics, University of Florence and Azienda Ospedaliera Vareggi, Via della Oblate 4, 50134 Florence, Italy.
Luzzi
Chiara
C
Lamanna
Caterina
C
Chiasserini
Veronica
V
Addante
Filomena
F
Desideri
Carla Maria
CM
Masotti
Giulio
G
Marchionni
Niccolò
N
Mannucci
Edoardo
E
D000368:Aged; D002219:Carbamates / Q000009:adverse effects; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000401:mortality*; D004338:Drug Combinations; D005260:Female; D005907:Gliclazide / Q000009:adverse effects; D005905:Glyburide / Q000009:adverse effects; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007558:Italy / Q000453:epidemiology; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D010880:Piperidines / Q000009:adverse effects
D002219:Carbamates; D004338:Drug Combinations; D007328:Insulin; D010880:Piperidines; C072379:repaglinide; D008687:Metformin; D005907:Gliclazide; D005905:Glyburide