Basal insulin and cardiovascular and other outcomes in dysglycemia.
BACKGROUND
The provision of sufficient basal insulin to normalize fasting plasma glucose levels may reduce cardiovascular events, but such a possibility has not been formally tested.


METHODS
We randomly assigned 12,537 people (mean age, 63.5 years) with cardiovascular risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes to receive insulin glargine (with a target fasting blood glucose level of ≤95 mg per deciliter [5.3 mmol per liter]) or standard care and to receive n-3 fatty acids or placebo with the use of a 2-by-2 factorial design. The results of the comparison between insulin glargine and standard care are reported here. The coprimary outcomes were nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure. Microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers were also compared between groups.


RESULTS
The median follow-up was 6.2 years (interquartile range, 5.8 to 6.7). Rates of incident cardiovascular outcomes were similar in the insulin-glargine and standard-care groups: 2.94 and 2.85 per 100 person-years, respectively, for the first coprimary outcome (hazard ratio, 1.02; 95% confidence interval [CI], 0.94 to 1.11; P=0.63) and 5.52 and 5.28 per 100 person-years, respectively, for the second coprimary outcome (hazard ratio, 1.04; 95% CI, 0.97 to 1.11; P=0.27). New diabetes was diagnosed approximately 3 months after therapy was stopped among 30% versus 35% of 1456 participants without baseline diabetes (odds ratio, 0.80; 95% CI, 0.64 to 1.00; P=0.05). Rates of severe hypoglycemia were 1.00 versus 0.31 per 100 person-years. Median weight increased by 1.6 kg in the insulin-glargine group and fell by 0.5 kg in the standard-care group. There was no significant difference in cancers (hazard ratio, 1.00; 95% CI, 0.88 to 1.13; P=0.97).


CONCLUSIONS
When used to target normal fasting plasma glucose levels for more than 6 years, insulin glargine had a neutral effect on cardiovascular outcomes and cancers. Although it reduced new-onset diabetes, insulin glargine also increased hypoglycemia and modestly increased weight. (Funded by Sanofi; ORIGIN ClinicalTrials.gov number, NCT00069784.).
Hertzel C
HC
Gerstein
Jackie
J
Bosch
Gilles R
GR
Dagenais
Rafael
R
Díaz
Hyejung
H
Jung
Aldo P
AP
Maggioni
Janice
J
Pogue
Jeffrey
J
Probstfield
Ambady
A
Ramachandran
Matthew C
MC
Riddle
Lars E
LE
Rydén
Salim
S
Yusuf
D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005215:Fasting; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000150:complications / Q000188:drug therapy*; D006760:Hospitalization; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000009:adverse effects / Q000627:therapeutic use*; D057194:Intention to Treat Analysis; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D015525:Fatty Acids, Omega-3; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D014280:Triglycerides; D000069036:Insulin Glargine; D002784:Cholesterol